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THERAPEUTICS: 


ITS 


PRINCIPLES   AND    PRACTICE. 


BY 

HORATIO  C.   WOOD,   M.D.,  LL.D.   (Lafayette,  Yale,  Pennsylvania), 

PROFESSOR     OF     MATERIA     MEDICA    AND     THERAPEUTICS     IN     THE     UNIVERSITY    OF     PENN- 
SYLVANIA ;    MEMBER    OF    THE    NATIONAL    ACADEMY    OF    SCIENCE. 

AND 

HORATIO  C.JVyOOD,  JR.,  M.D., 

DEMONSTRATOR   OF  PHARMACODYNAMICS  IN  THE   UNIVERSITY  OF  PENNSYLVANIA. 


THIRTEENTH   EDITION. 


THOROUGHLY    REVISED    AND    ADAPTED    TO    THE     EIGHTH 

(1905)    EDITION    OF   THE   UNITED    STATES 

PHARMACOPOEIA. 


PHILADELPHIA  AND  LONDON: 

J.  B.  LIPPINCOTT  COMPANY. 

1907. 


Entered,  according  to  act  of  Congress,  in  the  year  1875,  by 

J.  B.  LIPPINCOTT  &  CO., 
7n  ike  office  of  the  Librarian  of  Congress,  at  Washington, 

Copyright,  1879,  1882,  and  1883,  by  J.  B.  LIPPINCOTT  &  Co. 
Copyright,  1885,  by  J.  B.  LIPPINCOTT  COMPANY. 
Copyright,  1888,  by  J.  B.  LIPPINCOTT  COMPANY. 
Copvrieht,  1891,  by  J.  B.  LIPPINCOTT  COMPANY. 
Copyiight,  1894,  by  J.  B.  LIPPINCOTT  COMPANY 
Copyright,  1897,  by  J.  B.  LIPPINCOTT  COMPANY. 
Copyright,  1900,  by  J.  B.  LIPPINCOTT  COMPANY. 
Copyright,  1905,  by  J.  B.  LIPPINCOTT  COMPANY. 
Copyright,  1906,  by  J.  B.  LIPPINCOTT  COMPANY. 


CLECTROTYFED  AND  MINTED  BY  J.  B.   LIPPINCOTT  COMPANY,  PHILADELPHIA,   U.  8.  A. 


TO 

DR.  GEORGE  B.  WOOD,  LL.D -, 

THIS    BOOK 

IS   DEDICATED    BY   THE   AUTHOR,    HIS   NEPHEW, 

AS   A  TOKEN  OF   RESPECT  AND 

AFFECTION. 


PREFACE   TO   THE   THIRTEENTH   EDITION. 


THE  extraordinary  favor  with  which  the  Twelfth  Edition  of  this  work 
was  received  by  the  medical  profession,  exhausting  in  four  months  the 
entire  edition,  has  offered  an  opportunity  as  well  as  an  inspiration  for  the 
revision  of  the  work.  Among  the  more  important  alterations  which  have 
been  made  is  the  reconsideration  of  the  effects  of  alcohol  especially  upon 
the  circulation,  which  has  been  necessitated  by  very  recently  appearing 
researches  ;  a  more  elaborate  discussion  of  the  value  of  the  scopolamine- 
morphine  anaesthesia  ;  a  consideration  of  the  use  of  copper  for  the  purifi- 
cation of  water  ;  the  addition  of  an  article — written  by  Dr.  George  B. 
Wood — on  Dunbar's  hay-fever  antitoxin  ;  and  many  minor  alterations  of 
the  text  to  conform  with  pharmacological  researches  which  have  appeared 
within  the  last  year.  Besides  these  changes  an  important  innovation  has 
been  made  in  the  amplification  of  the  Disease  Index.  The  plan  which 
has  been  adopted  has  been  to  give  under  each  disease  a  list  of  the  drugs 
which  have  been  recommended,  with  a  short  summary  of  the  action  or  use 
of  the  various  remedies,  so  that  the  physician  can  tell  in  a  few  minutes 
which  medicine  is  most  likely  to  prove  useful  for  an  individual  case  under 
consideration.  It  is  hoped  by  this  means  that  the  Index  of  Diseases  will 
prove  in  fact  as  well  as  in  name,  a  guide  to  therapeutics. 

With  a  full  appreciation  of  the  kind  reception  with  which  this  work 
has  been  received  both  in  America  and  in  Europe,  the  Authors  have  used 
every  effort  in  their  power  to  make  the  work  deserving  of  the  confidence 
which  has  been  reposed  in  it. 

UNIVERSITY  OF  PENNSYLVANIA,  June,  1906. 


PREFACE   TO   THE   FIRST   EDITION. 


AT  the  present  time,  when  the  shelves  of  private  and  public  libraries 
are  groaning  beneath  their  ever-increasing  loads,  when  a  thousand 
presses  in  every  city  send  forth  day  and  night  their  printed  messages 
until  the  earth  is  filled  with  them,  it  seems  almost  presumptuous  for 
any  one  to  offer  new  volumes  to  the  world.  Indeed,  art  is  so  long,  life 
is  so  short,  that  every  student  has  the  right  to  demand  of  an  author  by 
what  authority  he  doeth  these  things,  and  to  challenge  every  memoir 
for  its  raison  d'etre.  This  being  so,  it  assuredly  will  not  appear  ego- 
tistical for  the  author  to  state  that  his  voluntary  task  was  first  suggested 
by  his  own  wants,  and  that  to  its  performance  he  has  brought  the  train- 
ing, labor,  and  experience  of  years  spent  in  the  laboratory,  the  study, 
the  class-room,  and  the  hospital  ward. 

There  are  a  number  of  excellent  treatises  upon  materia  medica  and 
therapeutics  ;  yet  in  various  attempts  at  original  research,  as  well  as  in 
the  ward  and  the  lecture-room  of  the  hospital,  I  have  keenly  felt  the 
want  of  something  more.  There  are  many  points  of  view  from  which 
a  subject  can  be  looked  at ;  there  are  many  paths  by  which  it  may  be 
approached  ;  and  to  me,  other  points  of  view,  other  modes  of  approach, 
have  been  far  more  enticing  than  those  adopted  in  our  standard  treatises. 

The  old  and  tried  method  in  therapeutics  is  that  of  empiricism,  or, 
if  the  term  sounds  harsh,  of  clinical  experience.  As  stated  by  one  of 
its  most  ardent  supporters,  the  best  possible  development  of  this  plan 
of  investigation  is  to  be  found  in  a  close  and  careful  analysis  of  cases 
before  and  after  the  administration  of  a  remedy,  and,  if  the  results  be 
favorable,  the  continued  use  of  the  drug  in  similar  cases.  It  is  evident 
that  this  is  not  a  new  path,  but  a  highway  already  worn  with  the  eager 
but  weary  feet  of  the  profession  for  two  thousand  years. 

That  very  much  has  been  thus  accomplished  it  were  folly  to  deny. 
Leaving  out  of  sight  the  growth  of  the  last  two  decades,  almost  all  of 
the  current  therapeutic  knowledge  has  been  gained  in  this  way. 

Therapeutics  developed  in  this  manner  cannot,  however,  rest  upon 
a  secure  foundation.  What  to-day  is  believed  is  to-morrow  to  be  cast 
aside,  certainly  has  been  the  law  of  advancement,  and  seemingly  must 
continue  to  be  so.  What  has  clinical  therapeutics  established  perma- 
nently and  indisputably  ?  Scarcely  anything  beyond  the  primary  facts 

vii 


viii  PREFACE   TO   THE   FIRST   EDITION. 

that  quinia  will  arrest  an  intermittent,   that  salts  will  purge,  and  that 
opium  will  quiet  pain  and  lull  to  sleep. 

To  established  therapeutic  facts  the  profession  clings  as  with  the 
heart  and  hand  of  one  man, — clings  with  a  desperation  and  unanimity 
whose  intensity  is  the  measure  of  the  unsatisfied  desire  for  something 
fixed.  Yet  with  what  a  Babel  of  discordant  voices  does  it  celebrate  its 
two  thousand  years  of  experience  ! 

This  is  so  well  known  that  it  seems  superfluous  to  cite  examples 
of  the  therapeutic  discord  ;  and  one  only  shall  be  mentioned, — namely, 
rheumatism.  In  this  disease,  bleeding,  nitrate  of  potassium,  quinine, 
mercurials,  flying  blisters,  purgation,  opium,  the  bromides,  veratria, 
and  a  host  of  other  remedies,  all  have  their  advocates  clamorous  for 
a  hearing  ;  and  above  all  the  tumult  are  to  be  heard  the  trumpet- 
tones  of  a  Chambers,  ' '  Wrap  your  patients  in  blankets  and  let  them 
alone. ' ' 

Experience  is  said  to  be  the  mother  of  wisdom.  Verily  she  has 
been  in  medicine  rather  a  blind  leader  of  the  blind  ;  and  the  history  of 
medical  progress  is  a  history  of  men  groping  in  the  darkness,  finding 
seeming  gems  of  truth  one  after  another,  only  in  a  few  minutes  to  cast 
each  back  to  the  vast  heap  of  forgotten  baubles  that  in  their  day  had 
also  been  mistaken  for  verities.  In  the  past,  there  is  scarcely  a  con- 
ceivable absurdity  that  men  have  not  tested  by  experience  and  for  a 
time  found  to  be  the  thing  desired  ;  in  the  present,  homoeopathy  and 
other  similar  delusions  are  eagerly  embraced  and  honestly  believed  in  by 
men  who  rest  their  faith  upon  experience. 

Narrowing  our  gaze  to  the  regular  profession  and  to  a  few  decades, 
what  do  we  see  ?  Experience  teaching  that  not  to  bleed  a  man  suffering 
from  pneumonia  is  to  consign  him  to  an  unopened  grave,  and  experience 
teaching  that  to  bleed  a  man  suffering  from  pneumonia  is  to  consign  him 
to  a  grave  never  opened  by  nature.  Looking  at  the  revolutions  and 
contradictions  of  the  past, — listening  to  the  therapeutic  Babel  of  the 
present, — is  it  a  wonder  that  men  should  take  refuge  in  nihilism,  and, 
like  the  lotos-eaters,  dream  that  all  alike  is  folly, — that  rest  and  quiet 
and  calm  are  the  only  human  fruition  ? 

Since  the  profession  has  toiled  so  long  and  found  so  little,  if  further 
progress  is  to  be  made  we  must  question  the  old  methods  and  search 
out  new  ones,  which  haply  may  lead  to  more  fruitful  fields.  In  the 
ordinary  affairs  and  business  of  life,  when  anything  is  to  be  accom- 
plished, the  effort  always  is  to  discover  what  is  to  be  done,  and  then 
what  are  the  means  at  command.  A  primary  knowledge  of  the  end  to 
be  accomplished,  and  a  secondary  acquaintance  with  the  instruments, 
are  a  necessity  for  successful  human  effort ;  and  until  the  sway  of  this 
law  is  acknowledged  by  physicians,  medicine  can  never  rise  from  the 
position  of  an  empirical  art  to  the  dignity  of  applied  science.  Until 
within  a  comparatively  recent  period,  it  has  been  impossible  to  comply 
with  this  law.  But,  through  the  advances  made  by  the  pathologists  and 


PREFACE   TO   THE   FIRST   EDITION.  ix 

by  the  students  of  the  natural  history  of  disease,  we  are  fast  learning 
the;  methods  in  which  nature  brings  the  body  back  to  health.  When 
this  is  done, — when  disease  is  thoroughly  understood, — we  shall  have 
wrought  out  the  first  element  of  the  problem,  shall  have  complied  with 
the  first  requirement  of  the  law. 

It  is  scarcely  within  the  province  of  a  therapeutist,  and  certainly  is 
not  possible  within  the  scope  and  limits  of  this  work,  to  discuss  at  length 
the  natural  history  of  disease  ;  but  it  is  allowable  to  point  out  evident  in- 
dications for  relief  ;  and  this  I  have  done  to  a  greater  or  less  extent 
throughout  the  book. 

The  work  of  the  therapeutist  is  chiefly  with  the  second  portion  of 
the  law.  Evidently,  it  is  his  especial  province  to  find  out  what  are  the 
means  at  command,  what  the  individual  drugs  in  use  do  when  put  into 
a  human  system.  It  is  seemingly  self-evident  that  the  physiological 
action  of  a  remedy  can  never  be  made  out  by  a  study  of  its  use  in  dis- 
ease. Under  all  circumstances,  the  problem  is  one  of  the  most  com- 
plex with  which  the  human  mind  has  to  grapple  ;  and  to  introduce  into 
this  problem  the  new  and  ever-varying  factors  of  the  effect  of  disease  and 
its  natural  vibrations  on  the  system  is  to  put  the  matter  beyond  human 
prescience. 

In  spite,  then,  of  Dr.  Niemeyer's  assertion  that  experiments  made  with 
medicaments  upon  the  lower  animals  or  upon  healthy  human  beings  have, 
as  yet,  been  of  no  direct  service  to  our  means  of  treating  disease,  and 
that  a  continuation  of  such  experiments  gives  no  prospect  of  such  ser- 
vice, it  is  certain  that  in  these  experiments  is  the  only  rational  scientific 
groundwork  for  the  treatment  of  disease.  We  must  discover  what  in- 
fluence a  drug  exerts  when  put  into  the  body  of  a  patient  before  we  can 
use  it  rationally  ;  and  we  can  gain  this  coveted  knowledge  only  in  the 
method  indicated. 

It  has  been  strenuously  objected,  especially  to  experiments  upon  ani- 
mals, that  drugs  do  not  act  upon  the  lower  creatures  in  the  same  manner 
as  they  do  upon  man.  When  I  first  commenced  the  studies  whose  out- 
come is  the  present  volume,  I  was  profoundly  impressed  with  the  truth 
of  this  oft-repeated  assertion  and  with  the  difficulties  which  it  put  in  the 
way.  To-day  I  do  not  believe  that,  stated  in  its  broad  sense,  it  is  true. 
Indeed,  more  strongly,  I  assert  that  it  is  not  true  ;  that,  in  the  vast 
majority  of  cases,  the  actions  of  drugs  upon  man  and  upon  the  lower 
animals  are,  though  seemingly  different,  in  reality  similar  ;  that  the  more 
knowledge  we  acquire  the  fewer  exceptions  remain  unexplained  ;  and 
that  the  whole  matter  is  in  all  probability  subject  to  laws  whose  devel- 
opment will  greatly  aid  in  our  explanation  of  various  obscure  clinical 
phenomena. 

The  general  proofs  of  these  assertions  are  sufficiently  obvious,  I 
think,  in  the  following  pages  to  render  it  unnecessary  for  me  to  dwell 
upon  them  at  length  here  :  moreover,  if  they  be  not  so  obvious  to  others 
as  to  myself,  space  is  here  wanting  for  a  full  discussion  of  the  subject. 


x  PREFACE   TO   THE   FIRST   EDITION. 

I  can  only  make  a  few  general  remarks,  and  point  out  some  of  what  I 
believe  to  be  the  governing  laws. 

In  the  first  place,  degree  and  quality  are  distinct  things,  and  should 
not  be  confounded.  Yet  they  frequently  are  ;  and  because  it  requires 
as  much  morphia  to  kill  a  pigeon  of  a  pound  weight  as  to  destroy  a  man, 
we  are  told  that  medicines  act  differently  upon  man  and  the  lower  ani- 
mals. Evidently  the  conclusion  is  a  non  sequitur,  and  difference  of  sus- 
ceptibility is  no  proof  of  difference  in  the  mode  of  impression.  A  tea- 
spoonful  of  Epsom  salt  may  purge  one  man,  while  it  may  require  ounces 
to  affect  another.  Evidently  there  is  a  difference  of  susceptibility  ;  but 
when  the  impression  is  once  made  it  is  of  the  same  character  in  each 
case.  As  with  man  and  man,  so  with  man  and  the  pigeon, — suscepti- 
bility is  no  measure  or  gauge  of  the  character  of  the  impression. 

A  large  number  of  drugs — indeed,  it  may  be  said,  the  larger  number 
of  important  drugs — exert  in  the  system  antagonistic  actions.  Thus, 
atropia  stimulates  the  spinal  cord,  but  destroys  the  conducting  power 
of  the  nerve-trunks.  It  is  evident  that  as  one  or  other  of  these  in- 
fluences predominates,  will  there  be  convulsions  or  paralysis.  Now,  if 
for  any  reason  one  animal  be  exceedingly  sensitive  to  the  spinal  action 
of  atropia,  that  animal  will  in  belladonna-poisoning  suffer  from  convul- 
sions, while  its  fellow,  which  is  affected  chiefly  by  the  nerve-action  of 
the  drug,  will,  under  like  circumstances,  have  paralysis.  Here  the  mere 
clinician,  with  his  superficial  knowledge,  seeing  the  paralyzed  and  the 
convulsed  lying  side  by  side,  says,  What  a  hopeless  muddle  !  Poor  fools, 
these  vivisectors  !  they  will  never  come  to  any  good  !  In  truth,  the  dif- 
ferences in  symptoms  in  these  and  in  many  other  cases  simply  depend 
upon  differences  in  susceptibility  ;  and  the  only  lesson  that  the  circum- 
stance teaches  is  the  importance  of  discovering  the  laws  which  govern 
these  susceptibilities. 

A  law  which  governs  the  susceptibility  to  the  action  of  drugs  is,  that 
the  more  highly  specialized  any  system  is  the  more  readily  affected  is  it 
by  a  medicine.  Thus,  the  cerebrum  of  a  man  is  far  more  highly  organ- 
ized than  that  of  any  other  animal,  and  consequently  he  is  far  more  sen- 
sitive to  the  action  of  drugs  which  affect  the  cerebrum  than  are  the  lower 
forms.  Again,  in  the  frog  the  spinal  system  is  especially  developed, — 
probably,  in  proportion  to  the  cerebrum,  more  so  than  in  any  other  of 
the  animals  commonly  experimented  with  :  consequently  the  batrachian 
is  excessively  sensitive  to  remedies  which,  like  strychnia,  affect  the  spinal 
cord.  In  obedience  to  this  law,  we  have  resulting  the  action  of  opium, 
— an  action  which  has  been  considered  the  strongest  proof  of  the  hope- 
lessness of  any  attempt  to  explain  the  effects  of  drugs  upon  a  man  by 
experiments  upon  the  lower  animals.  In  man,  opium  causes  deep  stupor 
and  general  relaxation  ;  in  the  frog,  it  causes  tetanic  convulsions.  The 
explanation  of  these  seeming  inconsistencies  is,  however,  very  evident 
when  the  whole  subject  is  looked  at.  Opium  in  all  animals  has  a  double 
action,  one  upon  the  cerebrum  and  one  upon  the  spinal  centres.  In  the 


PREFACE  TO   THE   FIRST   EDITION.  xi 

frog,  the  latter  being  the  more  highly  organized,  the  spinal  action  over- 
comes the  cerebral  ;  in  man,  the  cerebrum  being  the  more  sensitive, 
stupor  replaces  the  convulsions  :  yet  in  man  convulsions  sometimes  occur 
in  opium-poisoning,  and  in  the  frog  the  dose  can  be  so  managed  as  to 
cause  stupor. 

A  second  law  which  seems  to  hold  sway  over  the  action  of  drugs 
upon  different  animals  is  that  great  differences  of  function  in  a  system 
affect  its  relation  to  drugs  :  thus,  in  an  herbivorous  animal  the  aliment- 
ary canal  is  very  different  from  what  it  is  in  the  carnivora,  whose  diges- 
tive organs  in  turn  differ  from  those  of  man, — the  omnivore.  Medi- 
cines which  act  upon  the  alimentary  canal  are  apt  to  vary  in  their 
effects  upon  different  orders  of  animals. 

Converse  to  the  above  law  is  that  which  renders  systems  which  are 
little  specialized  similarly  acted  upon  by  drugs  in  different  classes  of 
animals. 

Thus,  the  general  structure  and  the  functions  of  the  circulatory 
system  are  very  uniform  among  vertebrates,  as  is  also  the  action  of 
those  drugs  which  affect  chiefly  the  circulation  :  thus,  aconite,  or  digi- 
talis, or  potash,  influences  in  the  one  way  the  heart  of  the  frog,  of  the 
rabbit,  and  of  man. 

There  are  a  very  few  apparent  exceptions  to  the  uniformity  of  the 
action  of  drugs  upon  all  animals  which  seemingly  contravene  the  laws 
that  have  been  mentioned.  These  exceptions  are  so  few,  however,  that 
without  doubt  advancing  knowledge  will  by  and  by  explain  them  all 
and  show  what  are  the  laws  which  for  the  time  being  hold  in  abeyance 
or  overcome  those  already  stated. 

An  asserted  fact  which  has  recently  been  brought  forward  as  re- 
vealing the  worthlessness  of  animal  experimentation  is  that  some 
monkeys  are  not  susceptible  to  the  action  of  strychnia,  while  others 
are.  Granting  the  truth  of  the  asserted  fact,  it  certainly  is  explainable. 
It  is  at  least  conceivable  that  a  given  species  of  animal  may,  by  the 
gradually  acquired  habit  of  feeding  upon  a  substance  containing  a  nar- 
cotic poison,  acquire  an  insusceptibility  to  the  influence  of  that  poison 
which  shall  as  it  were  belong  to  its  specific  type,  or,  in  other  words,  be 
an  acquired  specific  character.  The  nervous  system  of  the  opium-eater 
becomes  accustomed  to  the  stimulant,  and  it  is  not  impossible  that  a 
measure  of  the  habit  should  be  transmitted.  If  the  Darwinian  law  of 
the  gradual  evolution  by  the  survival  of  the  fittest  have  any  force,  these 
curious  apparent  freaks  of  medicines  in  regard  to  their  physiological 
action  may  be  the  result  of  this  law,  especially  since  it  is  species  which 
are  affected.  It  is  not  all  monkeys  that  are  proof  against  strychnia,  but, 
as  we  are  distinctly  told,  only  one  species  of  monkey  ;  and,  so  far  as  I 
know,  it  is  not  all  deer  that  are  said  to  thrive  when  fed  upon  tobacco, 
but  only  the  Virginia  deer.  Whether  this  conception  be  or  be  not  a 
mere  fancy,  this  much  is  to  my  mind  very  clear,  that  the  few  scattered'ex- 
ceptions  ought  not  to  outweigh  the  immense  mass  of  evidence  upon  the 


xii  PREFACE  TO   T.HE   FIRST   EDITION. 

other  side,  and  that  it  is  inconceivable  that  drugs,  in  their  relations  to 
animal  organisms,  differ  from  all  other  created  things  in  not  being  subject 
to  law. 

In  the  early  portion  of  this  preface  I  stated  that  the  work  had 
grown  out  of  a  need  felt  by  myself  :  that  need  was  for  a  book  into 
which  should  be  gathered  the  many  scattered  facts  in  regard  to  the 
physiological  action  of  medicine, — a  book  in  which  an  attempt  should 
be  made  to  sift  the  true  from  the  false,  to  reconcile  seeming  differences, 
to  point  out  what  we  know  and  what  we  do  not  know,  and  to  give  a 
platform  from  which  investigators  might  start  forward  without  the  ne- 
cessity of  being,  as  is  so  often  the  case,  ignorant  of  what  was  already 
achieved,  or  of  spending  a  great  deal  of  time  in  a  wild  hunt  through 
the  almost  boundless,  but  often  scattered  and  inaccessible,  ranges  of 
Continental  literature. 

The  plan  of  the  present  work  has  been  to  make  the  physiological 
action  of  remedies  the  principal  point  in  discussion.  A  thoroughly 
scientific  treatise  would  in  each  article  simply  show  what  the  drug  does 
when  put  into  a  healthy  man,  and  afterwards  point  out  to  what  diseases 
or  morbid  processes  such  action  is  able  to  afford  relief.  Unfortunately, 
in  the  great  majority  of  cases  our  knowledge  is  not  complete  enough  for 
this,  and  the  clinical  method  has  to  be  used  to  supplement  the  scientific 
plan. 

I  have  added  to  the  book  a  consideration  of  toxicology,  so  far  as  it 
is  of  interest  to  the  physician.  This  has  been  done  for  several  reasons. 
First,  it  was  necessary  to  study  the  action  of  poisonous  drugs  upon  man, 
in  order  to  make  out  their  physiological  action  ;  secondly,  physicians 
are  constantly  required  to  diagnosticate  and  to  treat  cases  of  poisoning  ; 
thirdly,  it  is  often  of  the  greatest  importance  for  a  medical  man  in  a 
court  of  law  to  be  able  to  state  what  are  the  symptoms  and  post-mortem 
appearances  produced  by  a  given  poison,  what  diseases  they  simulate, 
and  how  far  and  in  what  they  differ  from  the  phenomena  of  these 
diseases.  That  part  of  the  science  of  toxicology  which  treats  of  the 
recognition  of  poisons  in  the  cadaver,  or  in  food  and  drink,  belongs  to 
the  domain  of  the  chemist,  and  I  have  avoided  it  altogether.  For  a 
similar  reason,  in  the  sections  on  materia  medica,  the  chemical  relations 
of  mineral  substances  have  not  been  discussed  at  all. 


ABBREVIATIONS. 


A.  A. — Archiv  fur  Augenheilkunde. 
A.  A.  P. — Archiv    fur    Anatomic    und 

Physiologic. 

A.  C.  J. — American  Chemical  Journal. 
A.  D.  S. — Archiv  fur  Dermatologie  und 

Syphilis. 
A.  de  P. — Archives  de  Physiologic  nor- 

male  et  pathologique. 
A.  E.  P.  P. — Archiv  fur  experimentelle 
Pathologic  und  Pharma- 
kologie. 
A.  G.  M. — Archives  ge'ne'rales  de  Me"de- 

cine. 

A.  G.  P. — Archiv  fur  die  gesammte 
Physiologic  des  Menschen 
und  der  Thiere. 

A.  Hk. — Archiv  der  Heilkunde. 
A.  I.  B. — Archives    italiennes   de    Bio- 
logic. 
A.  I.  M.  N. — Archivio    italiano    per    le 

malattie  nervose. 

A.  I.  Past. — Annales  de  PInstitut  Pas- 
teur. 
A.  I.  P. — Archives    internationales    de 

Pharmacodynamie. 
A.  J.  M.  S. — American   Journal    of   the 

Medical  Sciences. 

A.  J.  P. — American    Journal  of    Physi- 
ology'. 
A.  K.  C. — Archiv    fur    klinische     Chi- 

rurgie. 
Al.  Z.  Ps. — Allgemeine    Zeitschrift    fur 

Psychiatric. 

A.  M.  Ex. — Archives  de  Me'decine  ex- 
pe'rimentelle     et    d' Ana- 
tomic pathologique. 
Amer.  Med. — American  Medicine. 
Am.  Lan. — American  Lancet. 
A.  N. — Alienist  and  Neurologist. 
An.  d'H. — Annales  d' Hygiene. 
An.  O. — Annals  of  Ophthalmology. 
Ann.  O. — Annales  d'Oculistique. 
A.  Op. — Archiv  fur  Ophthalmologie. 
A.  of  Op. — Archives  of  Ophthalmology. 
A.  Ph. — Archiv      fur      Anatomic    und 
Physiologic,  physiologisches 
Abteilung. 

A.  Pharm. — Archives  de  Pharmacody- 
namie. 


A.  R. — Aerztliche  Rundschau. 

A.  S.  Z. — Aerztliche  Sachverstandigen- 

Zeitung. 

Aus.  M.  Gaz. — Australian  Medical  Ga- 
zette. 

Aus.  M.  J. — Australian  Medical  Journal. 

A.  V.  K. — Archiv      fur       Verdauungs- 

Krankheiten. 

A.  Z. — Apotheker-Zeitung. 

B.  A.  M.— Bulletin   de    P  Academic   de 

Me'decine  de  Paris. 

B.  A.  R.  B.— Bulletin  de  1' Academic 
Royale  de  Me'decine  de 
Beige. 

B.  G.  T.— Bulletin  ge"ne"ral  de  The"rapeu- 
tique  me"dicale  et  chirurgi- 
cale. 
B.  K.  Ch. — Beitrage      zur       klinischen 

Chirurgie. 
B.  K.  W. — Berliner  klinische  Wochen- 

schrift. 

B.  M. — Le  Bulletin  Me"dicale. 
B.  M.  J.— British  Medical  Journal. 
B.  M.  S.  C.  P.— Bulletin    et    Me"moires 
de    la  Socie'te'  Clin- 
ique  de  Paris. 

B.  M.  S.  H.— Bulletin  Socie'te'  Me"dicale 
des  Hopitaux  des  Paris. 
B.  M.S.  J. — Boston  Medical  and  Surgi- 
cal Journal. 

B.  P.  A. — Beitrage  zur  Pathologischen 

Anatomic  und   zur  Allge- 
meinen  Pathologic. 

Cb.  B. — Centralblatt  fur  Bacteriologie. 
Cb.  C. — Centralblatt  fur  Chirurgie. 
Cb.  I.  M.— Centralblatt  fur  Innere  Medi- 

cin. 
Cb.  N.— Centralblatt     fur     Nervenheil- 

kunde. 
Cb.  P.— Centralblatt  fur  Physiologic. 

C.  B.  S.  A. — Correspondenzblatt       der 

Schweizerische  Aerzte. 
Chi.  M.  J. — Chicago  Medical  Journal. 
C.  K.  M.— Centralblatt     fiir     klinische 

Medicin. 

Cl.  M. — Clinica  Moderna. 
Cl.  M.  I. — La  Clinica  Medicale  Italienne. 
C.  M.  J.  E. — Chicago    Medical    Journal 

and  Examiner. 


XIII 


XIV 


ABBREVIATIONS. 


C.  M.  R.  V.— Contributions  to  Medical 
Research.      Vaughn. 
Ann  Arbor.    1903. 
C.  M.  W.— Centralblatt     fur     medicin- 

ischen  Wissenschaften. 
C.     R.     A.     S. — Comptes-rendus      de 
1'Acade'mie  de  Sci- 
ence, Paris. 

C.  R.    S.    B.— Comptes-rendus    de    la 

Socie"te  de   Biologic, 
Paris. 

D.  A.    K.    M. — Deutsches    Archiv    fiir 

klinische  Medicin. 

D.  C. — Dermatologisches  Centralblatt. 
D.  J.   M.   S.— Dublin    Journal    of    the 

Medical  Sciences. 
D.  Kl.— Deutsche  Klinik. 
D.  M.  W. — Deutsche  medicinische  Wo- 

chenschrift. 

D.    Z.    Ch — Deutsche    Zeitschrift    fiir 
Chirurgie. 

D.  Z.  N — Deutsche  Zeitung  fiir  Nerven- 

heilkunde. 
Ed.  M.  J. — Edinburgh  Medical  Journal. 

E.  M.  N.— L'Echo  Medical  du  Nord. 
Fort.  M. — Fortschritte  der  Medicin. 

G.  A.  M.  T.— Giornale  della  Reale 
Academia  di  Medi- 
cina  di  Torino. 

G.  H.  M.  C. — Gazette  Hebdomadaire de 
M£decine    et    de    Chi- 
rurgie. 
G.  I.  M.  P. — Gazzeta  Internazionale  de 

Medecina  Practica. 

G.  K.  H. — Monatsberichte  iiber  die 
gesammtleistungen  auf 
dem  Gebeite  der  Krank- 
heiten  des  Ham  und  Sex- 
ual-Apparates. 

G.  M.  P.— Gazette  Mddicale  de  Paris. 
Gl.  M.  J. — Glasgow  Medical  Journal. 
Guy    H.    R.— Guy's       Hospital       Re- 
ports. 

Hk.— Die  Heilkunde. 
H.  S.  Jb. — Hoffmann  and  Schwalbe's 
Jahresberichte    iiber    die 
Fortschritte  der  Anatomic 
und  Physiologic. 
I.  B.  I.  M. — Internationale  Beitrage  zur 

Inneren  Medicin. 
In.  Dis. — Inaugural  Dissertation. 
J.  A.  M.  A. — Journal    of  the  American 

Medical  Association. 
J.  A.  P. — Journal  of  Anatomy  and  Phys- 
iology. 


J.  Chem.  S.— Journal  of   the  Chemical 

Society  of  London. 
J.  de  1'A.  P. — Journal  de  1'Anatomie  et 

Physiologic. 
J.  de  P.  P. — Journal  de  Physiologic  et  de 

Pathologie  Generale. 
J.  de  Th. — Journal  de  The"rapeutique. 
J.    Ex.    M. — Journal    of    Experimental 

Medicine. 

J.  M.  R. — Journal  of  Medical  Research. 
J.  N.  M.  D. — Journal  of    Nervous    and 

Mental  Diseases. 
J.  P. — Journal  of  Physiology. 
J.  Pr. — Journal  des  Praticiens. 
J.  P.  and  B. — Journal  of  Pathology  and 

Bacteriology. 
K.      T.      W. — Klinisch-Therapeutische 

Wochenschrift. 
L.  L. — London  Lancet. 
Lyon  M. — Lyon  Me"dicale. 
L.  M.  R. — London  Medical  Recorder. 
L.  S. — Lo  Sperimentale. 
M.  A. — Merck's  Archives. 
M.    C.    C. — Medicinische-Chirurgisches 

Centralblatt. 

M.  C.  Tr. — Medico-Chirurgical  Transac- 
tions. 

Med.  R. — Medical  Register. 
M.  H.  H.  B. — Marine  Hospital  Hygienic 

Laboratory  Bulletin. 
M.    M.    W. — Miinchener  medicinische 

Wochenschrift. 
M.  News. — Medical  News. 
M.  N.  A.  S. — Memoirs  of  the  National 

Academy  of  Science. 
M.    P.   D. — Monatshefte  fiir  praktische 

Dermatologie. 
M.  P.  N. — Monatsschrift  Psychiatric  und 

Neurologic. 

M.  R.— Merck's  Report. 
M.  S.  Rep.— Medical  and  Surgical  Re- 
porter. 

M.  T.  G.— Medicarl  Times  and  Gazette. 
M.  W. — Medicinische  Wochenschrift. 
N.  Cb. — Neurologisches  Centralblatt. 
N.  O.  M.  J. — New  Orleans  Med.  Journal. 
N.  Y.  M.  J.— New  York  Medical  Journal. 
N.  Y.  M.  R.— New  York  Med.  Record. 
N.  Y.  M.  T.— New  York  Medical  Times. 
O.  M.  R. — Ohio  Medical  Recorder. 
O.  R. — Ophthalmic  Record. 
Pa.  M.  S.  J. — Pacific  Medical  and  Sur- 
gical Journal. 

Path.  Intern. — Pathologie  Interne. 
Ph.  Post. — Pharmaceutical  Post. 


ABBREVIATIONS. 


xv 


P.  J.  and  Tr. — Pharmaceutical    Journal 

and  Transactions. 
P.  M.  C.  P. — Pester  medizinisch  Chirur- 

gische  Presse. 

P.  M.  J. — Philadelphia  Medical  Journal. 
P.  M.  T — Philadelphia  Medical  Times. 
P.  P.  S.  L.— Proceedings  of  the  Physio- 
logical Society  of  Lon- 
don. 

Pract. — Practitioner. 
Press.  M.  B. — La  Presse  Me"dicale  Bel- 

gique. 
Pr.  M.  W. — Prager  medicinische  Wo- 

chenschrift. 

Prog.  M.— Le  Progres  Medicale. 
P.  Tr.  R.  S.  L.— Philosophical  Transac- 
tions   of    the    Royal 
Society  of  London. 

Q.  J.  P.  M. — Quarterly  Journal  of  Psy- 
chological Medicine  and 
Medical  Jurisprudence. 
R.  C. — Revue  de  Chirurgie. 
R.   M.  S.   R.— Revue  Medicale  de   la 

Suisse  Romande. 
R.  Med. — Revue  de  Medecine. 
Rif.  M. — La  Riforma  Medica. 
R.  T. — Revue  de  Therapeutique. 
Sb.  G.  W. — Sitzungsberichte  der  konig- 
liche     Gesellschaft     der 
Wissenschaften. 

S.  Jb. — Schmidt's  Jahrbiicher  der  in-  und 
auslandischen  gesammten 
Medicin. 

S.  M — La  Semaine  Medicale. 
St.  L.  C.  R.— St.  Louis  Clinical  Record. 
St.  L.  M.  S.  J.— St.  Louis  Medical  and 

Surgical  Journal. 

S.  L.  P.  C.  Y.— Studies  from  the  Labora- 
tory of  Physiological 
Chemistry  of  Yale 
University'. 

St.  P.  M.  W.— St.  Petersburger  medi- 
cinische Wochen- 
schrift. 

T.  G. — Therapeutic  Gazette. 
Ther.  Geg. — Die  Therapie  der  Gegen- 

wart. 

Th.  M. — Therapeutische  Monatshefte. 
T.  M. — Therapeutic  Monthly. 
Tr.  A.  O.  S.— Transactions  of  the  Amer- 
ican   Ophthalmological 
Society. 

Tr.  I.  C.  C. — Transactions  of  the  Inter- 
national Congress  of 
Charity,  Corrections, 
and  Philanthropy. 


Tr.  P.  C.  M.  S.— Transactions  of  the 
Philadelphia  County 
Medical  Society. 

Tr.  R.  S.  Ed.— Transactions  of  the  Royal 
Society  of  Edinburgh. 
T.  W. — Therapeutische  Wochenschrift. 
U.  M.  M. — University    Medical    Maga- 
zine. 

U.  N.  M.  T. — Untersuchungen  zur  Na- 
turlehre  des  Menschen 
und  der  Thiere.  Mole- 
schott. 

U.  P.  L.  W. — Untersuchungen  aus  den 
Physiologisches  Labo- 
ratorium  zu  Wiirzburg. 
U.  P.  M.  B. — University  of  Pennsylva- 
nia Medical  Bulletin. 
V.  A.  P.  A. — Virchow's  Archiv  fiir  path- 
ologische  Anatomic  und 
Physiologic. 
V.  A.  S. — Verein  der  Aerzte  in  Steier- 

mark. 
V.  C.  M. — Verhandl.  des  Congresses  fiir 

Innere  Medizin. 

V.  V.  N.  K.  I.  M.— Verhandlungen  des 
Vierten  Nord- 
ischen  Kongresses 
fiir  Innere  Medi- 
zin. 

W.  A.  W. — Sitzungsberichte  der  kaiser- 
lichen  Akademie  der  Wis- 
senschaften     zu      Wien. 
Math.  Naturwiss.  Kl. 
W.  G.  H. — Wochenschrift  fiir    die    ge- 

sammte  Heilkunde. 

Wb.  G.  A.  W.—  Wochenblatt  der  k.  k. 
Gesellschaft  der 
Aerzte  in  Wien. 

W.  K.  R. — Wiener  klinische  Rundschau. 
W.  K.  W. — Wiener  klinische  Wochen- 
schrift. 

W*.  M.  Bl. — Wiener  medicinische  Blat- 
ter. 

W.  M.  P. — Wiener  medicinische  Presse. 
Z.  B. — Zeitschrift  fiir  Biologic. 
Z.  C.  P.  P.— Zeitschrift   (Beitrage)    zur 
Chemischen  Physiologic 
und  Pathologic. 
Z.  F.  H.  I — Zeitschrift  fiir  Hygiene  und 

Infectionskrankheiten. 
Z.  K.  M. — Zeitschrift  fiir  klinische  Medi- 
cin. 
Z.  Mb. — Zeitschrift       fiir       Medicinal- 

beamte. 

Z.  P.  C. — Zeitschrift  fiir  physiologische 
Chemie. 


TABLE    OF    CONTENTS. 


PART  I. 

REMEDIES,  REMEDIAL  MEASURES,  AND  REMEDIAL  METHODS 
WHICH  ARE  NOT  DRUGS. 

PAGE 

CHAPTER  I. — General  Considerations  ;  Massage  ;  Feeding  of  the  Sick,  includ- 
ing General  Considerations,  Liquid  Meat  Foods,  Milk  Foods,  Artificially 
Digested  Foods i 

CHAPTER  II. — The  Treatment  of  Systemic  States,  including  Exhaustion  and 

Neurasthenic  Conditions,  Corpulence,  and  Lithiasis 16 

CHAPTER  III. — CALORIC  :  Local  Use  of  Heat ;  General  Use  of  Heat ;  Local 

Employment  of  Cold  ;  Cold  as  a  Tonic  and  Stimulant ;  Cold  in  Pyrexia  28 

CHAPTER  IV. — ELECTRICITY  :  General  Considerations,  including  Electrical 
Physics  and  Physiology  as  applied  to  Human  Medicine  ;  Employment  of 
Electricity  for  the  Diagnosis,  Prognosis,  and  Therapeusis  of  Motor  and 
Sensory  Affections  ;  Application  of  Electricity  to  the  Nerve-Centres,  and 
Use  as  a  Tonic  ;  Magnetism 41 

PART  II. 

DRUGS. 

Preliminary  Considerations  ;  Pharmacy  ;  Therapeutics  ;  Pharmacology  ;  Prep- 
arations ;  Indications  for  the  Use  of  Medicine  ;  General  Methods  of  Thera- 
peutics, including  Homoeopathy  ;  Modes  of  Administration  ;  Doses,  and 
the  Circumstances  that  modify  them  ;  the  Art  of  Prescribing  and  Com- 
bining Medicines  ;  Incompatibilities  ;  Classification 60 

DIVISION  I.— SYSTEMIC   REMEDIES. 

CLASS  I.— GENERAL  REMEDIES. 

ORDER   I.— NERVINES. 

FAMILY  I. — ANTISPASMODICS  :  Musk  ;  Valerian  ;  Ammonium  Valerianate  ; 
Valyl ;  Validol ;  Validolum  Camphoratum  ;  Asafcetida  ;  Hoffmann's 
Anodyne  ;  Hops  ;  Lactucarium  ;  Cimicifuga  ;  Cypripedium  ;  Acetic 
Ether  ;  Sumbul 73 

FAMILY  II. — ANESTHETICS  :  Nitrous  Oxide  ;  Somnoform  ;  Ether  ;  Chloro- 
form ;  Ethyl  Chloride  ;  Ethyl  Bromide  ;  Methyl  Bromide  ;  Pental ;  Methy- 
lene  Bichloride  ;  Practical  Anaesthesia  ;  Local  Anaesthesia  :  Eucaine  ; 
Tropacocaine  ;  Anaesthesin  ;  Orthoform  ;  Stovaine  ;  Alypin  ;  Nirvanin  ; 
Practical  Local  Anaesthesia 82 

FAMILY  III. — SOMNIFACIENTS  :  Opium  ;  Morphine  ;  Codeine  ;  Peronine  ;  Dio- 
nin ;  Heroin ;  Chloretone ;  Amylene  Hydrate ;  Ethyl  Carbamas ; 
Amylene  Chloral ;  Methylal ;  Hedonal ;  Isopral ;  Veronal ;  Hypnone  ; 
Chloralformamid  ;  Chloralose  ;  Butyl-chloral  Hydrate  ;  Chloral ;  Sul- 
phonal ;  Tetronal ;  Trional ;  Paraldehyde  ;  Amylene  Hydrate  ;  Urethan  .  125 

FAMILY  IV. — DELIRIFACIENTS  :  Belladonna  Leaf  and  Belladonna  Root ; 
Atropine  ;  Hyoscyamus  ;  Hyoscyaminae  Sulphas  ;  Scopola  ;  Hyoscinae 
Hydrobromidum  ;  Homotropinae  Hydrobromidum  ;  Cannabis  Indica  ; 
Coca 167 


xviii  TABLE  OF  CONTENTS. 

PAGE 

FAMILY  V. — EXCITO-MOTORS  :  Nux  Vomica  ;  Strychnine;  Brucine  ....  211 
FAMILY  VI. — DEPRESSO-MOTORS  :  Calabar  Bean  ;  Potassium  Bromide  ;  Am- 
monium Bromide  ;  Sodium  Bromide  ;  Strontium  Bromide  ;  Calcium  Bro- 
mide ;  Lithium  Bromide  ;  Hydrobromic  Acid  ;  Bromal  Hydrate  ;  Bromo- 
form  ;  Gold  Bromide  ;  Bromolene  ;  Bromipin  ;  Bromocoll ;  Bromalin  ; 
Amyl  Nitrite  ;  Ethyl  Nitrite  ;  Potassium  Nitrite  ;  Sodium  Nitrite  ;  Nitro- 
glycerin  ;  Erythral  Tetranitrate  ;  Lobelia  ;  Gelsemium  ;  Tobacco  ; 

Conium      230 

FAMILY  VII. — RESPIRATORY  STIMULANTS  AND  DEPRESSANTS  :  Aspido- 
sperma  ;  Aspidospermatine  ;  Aspidosamine  ;  Quebrachine  ;  Hypoque- 
brachine  ;  Quebrachamine 276 

ORDER   II.— CARDIANTS. 

FAMILY  I. — CARDIAC  STIMULANTS  :  Ammonium  and  its  Salts  ;  Camphor  ; 
Oil  of  Camphor  ;  Camphoric  Acid  ;  Alcohol ;  Methyl  Alcohol ;  Digitalis  ; 
Apocynum  ;  Strophanthus  ;  Caffeine  ;  Convallaria  Majalis  ;  Sparteine  ; 
Adonidin 279 

FAMILY  II. — CARDIAC  DEPRESSANTS  :  Antimony  and  its  Salts ;  Veratrum 
Viride  ;  Veratroidine  and  Jervine  ;  Veratrum  Album  ;  Veratrine  ;  Arnica  ; 
Aconite  ;  Aconitine  ;  Hydrocyanic  Acid  ;  Silver  Cyanide  ;  Cyanogen  ; 
Bitter  Almonds  ;  Benzaldehyde  ;  Tartaric  Acid  ;  Citric  Acid  ;  Lemon- 
Juice  ;  Acetic  Acid  ;  Vinegar  ;  Oxalic  Acid 359 


ORDER   III.— NUTRIANTS. 

FAMILY  I. — ASTRINGENTS  :  Tannic  Acid  ;  Tannalbin  ;  Ichthyol ;  Ichthalbin  ; 
Isarol ;  Gallic  Acid  ;  Galls  ;  Gambir  ;  Kino  ;  Haematoxylon  ;  Rhatany  ; 
Hamamelis  ;  Oak  Bark  ;  Red  and  Pale  Rose  ;  Geranium  ;  Rhus  Glabra  ; 
Agaric  ;  Cotarnine  ;  Alum  ;  Aluminii  Sulphas  ;  Aluminii  Hydroxidum  ; 
Lead,  its  Salts  and  Preparations  ;  Bismuth,  its  Salts  and  Preparations ; 
Cerii  Oxalas  ;  Zinc,  its  Salts  and  Preparations  ;  Copper,  its  Salts  and 
Preparations  ;  Silver,  its  Salts  and  Preparations 402 

FAMILY  II. — TONICS  :  Iron,  its  Salts  and  Preparations  ;  Manganese,  its  Salts 
and  Preparations  ;  Sulphuric  Acid  ;  Hydrochloric  Acid  ;  Nitric  Acid  ; 
Nitro- Hydrochloric  Acid  ;  Lactic  Acid 443 

FAMILY  III. — ALTERATIVES  :  Phosphorus  ;  Zinc  Phosphide  ;  Arsenic  and  its 
Preparations  ;  Mercury,  its  Salts  and  Preparations  ;  Gold  Salts  ;  Iodine, 
its  Salts  and  Preparations  ;  lodoform  ;  lodol ;  lodipin  ;  Aristol ;  Noso- 
phen  ;  Europhen  ;  Soziodol ;  lodoformogen  ;  Cod-Liver  Oil ;  Phosphoric 
Acid  ;  Calcium  Phosphate  ;  Hypophosphites  ;  Colchicum  Seed  and  Col- 
chicum  Root ;  Tannacol ;  Tannopine  ;  Tannoform  ;  Sarsaparilla  ;  Guaiac 
Wood  and  Guaiac  Resin  ;  Mezereum  ;  Jambul ;  Thiosinamine  ;  Taraxa- 
cum ;  Stillingia  ;  Xanthoxylum  ;  Animal  Drugs :  Nuclein  ;  Gelatin  ; 
Thyroid  Body  ;  Suprarenal  Capsules  ;  Pituitary  Body  ;  Spleen  ;  Thymus 
Gland  ;  Toxins  and  Antitoxins  .  ....  459 

FAMILY  IV. — ANTIPERIODICS  :  Cinchona  and  its  Alkaloids  ;  Warburg's  Tinc- 
ture ;  Methylene-Blue  ;  Eucalyptus 557 

FAMILY  V. — ANTIPYRETICS  :  Salicylic  Acid  ;  Oil  of  Gaultheria  ;  Aspirin  ; 
Mesotan  ;  Glycosal ;  Salicylic  Amylester  ;  Salicin  ;  Salophen  ;  Antipyrin  ; 
Acetopyrine  ;  Eupyrine  ;  Acetanilid  ;  Phenacetin  ;  Phenocoll  Hydrochlo- 
ride  ;  Exalgine  ;  Salipyrin  ;  Pyramidon  ;  Thermol ;  Pyrosal 586 


TABLE  OF  CONTENTS.  xbc 

CLASS  II.— LOCAL  REMEDIES. 

PAGE 

FAMILY  I. — STOMACHICS  :  Quassia  ;  Gentian  ;  Columbo  ;  Chirata  ;  Berberis  ; 
Wild  Cherry  Bark  ;  Cinnamon  ;  Aromatic  Fluidextract ;  Cloves  ;  Nut- 
meg ;  Mints  ;  Allspice  ;  Cardamoms  ;  Ginger  ;  Black  Pepper  ;  Capsicum  ; 
Oil  of  Cajuput ;  Oil  of  Sassafras ;  Orange  Peel  and  Orange  Flowers ; 
Umbelliferous  Aromatics  ;  Chamomile  ;  Serpentaria  ;  Cascarilla  ....  621 

FAMILY  II. — EMETICS  :  Ipecacuanha  ;  Apomorphine  ;  Mustard  ;  Zinc  Sulphate     632 

FAMILY  III. — CATHARTICS  :  Manna  ;  Frangula  ;  Fel  Bovis  ;  Cascara  Sagrada  ; 
Euonymus  ;  Leptandra  ;  Tamarind  ;  Cassia  Fistula  ;  Magnesia  ;  Sul- 
phur ;  Sulphurated  Potassa  ;  Sulphurated  Lime  ;  Castor  Oil ;  Mercurials  ; 
Rhubarb  ;  Aloes  ;  Senna  ;  Magnesium  Sulphate  ;  Solution  of  Magnesium 
Citrate ;  Granulated  Magnesium  Citrate  ;  Sodium  Sulphate ;  Sodium 
Phosphate  ;  Rochelle  Salt ;  Seidlitz  Powder  ;  Jalap  ;  Colocynth  ;  Scam- 
mony  ;  Compound  Cathartic  Pills  ;  Podophyllum  ;  Elaterium  ;  Gamboge  ; 
Croton  Oil 644 

FAMILY  IV. — DIURETICS  :  Squill ;  Scoparius  ;  Calomel  ;  Theobromine  and 
other  Xanthin  Compounds  ;  Agurin  ;  Theophyllin  ;  Sweet  Spirit  of  Nitre  ; 
Digitalis  ;  Sugar  ;  Potassium  and  its  Salts  ;  Lithium  and  its  Salts  ;  Piper- 
azine  ;  Lycetol ;  Urotropin  ;  Quinic  Acid  ;  Piperazine  Quinate  ;  Urotropin 
Quinate  ;  Lithium  Quinate  ;  Helmitol ;  Hetralin  ;  Urasol ;  Strontium  and 
its  Salts  ;  Buchu  ;  Pareira  ;  Uva  Ursi ;  Chimaphila  ;  Triticum  ;  Juniper ; 
Oil  of  Erigeron  ;  Oil  of  Sandal- Wood  ;  Canada  Turpentine  ;  White  Tur- 
pentine ;  Oil  of  Turpentine ;  Chian  Turpentine ;  Copaiba ;  Cubebs ; 
Matico  ;  Cantharides  ;  Kava  ;  Yohimbine 678 

FAMILY  V. — DIAPHORETICS  :  Turkish  Baths  and  Russian  Baths  ;  Jaborandi ; 

Dover's  Powder  ;  Sweet  Spirit  of  Nitre  ;  Spirit  of  Mindererus 717 

FAMILY  VI. — EXPECTORANTS  :  Atomization  ;  Lobelia  ;  Ipecacuanha  ;  Tartar 
Emetic ;  Ammonium  Chloride  ;  Grindelia  ;  Balsam  of  Peru  ;  Balsam  of 
Tolu  ;  Garlic  ;  Squill ;  Tar  ;  Terebene  ;  Oil  of  Sandal- Wood  ;  Saponine  ; 
Senega  ;  Quillaja  ;  Ammonise  ;  Marrubium  ;  Sanguinaria  ;  Sulphuretted 
Hydrogen 730 

FAMILY  VII. — EMMENAGOGUES  :  Griffith's  Mixture  ;  Potassium  Permanga- 
nate ;  Cantharides  ;  Guaiac  ;  Savine  ;  Rue  ;  Tanacetum  ;  Pennyroyal ; 
Apiol ;  Viburnum  Opulus  ;  Viburnum  Prunifolium 741 

FAMILY  VIII. — OXYTOCICS  :  Ergot ;  Hydrastis  ;  Hydrastine  ;  Hydrastinine  ; 

Cotton-Root 745 

FAMILY  IX. — IRRITANTS  AND  COUNTER-IRRITANTS  :  Soft  Soap ;  Chrysaro- 
bin  ;  Cantharides  ;  Mustard  ;  Capsicum  ;  Oil  of  Turpentine  ;  Ammonia  ; 
Burgundy  Pitch  ;  Carbon  Disulphide 765 

FAMILY  X. — ESCHAROTICS  :  Caustic  Potash  ;  Vienna  Paste  ;  Arsenous  Acid  ; 
Zinc  Chloride ;  Corrosive  Sublimate ;  Solution  of  Mercuric  Nitrate ; 
Sulphuric  Acid  ;  Nitric  Acid  ;  Chromic  Acid  ;  Bromine  ;  Zinc  Sulphate  ; 
Copper  Sulphate  ;  Burnt  Alum  ;  Pyrogallic  Acid 776 

FAMILY  XI. — DEMULCENTS  :  Gum  Arabic  ;  Tragacanth  ;  Slippery  Elm  ; 
Irish  Moss  ;  Licorice  Root ;  Starch  ;  Flaxseed  ;  Sassafras  ;  Althaea  ;  Ice- 
land Moss ;  Barley 782 

FAMILY  XII. — EMOLLIENTS  :  Lard  ;  Oil  of  Sweet  Almonds  ;  Cacao  Butter ; 
Linseed  Oil ;  Olive  Oil ;  Oleic  Acid  ;  Lanolin  ;  Glycerin  ;  Saccharin  ; 
Petrolatum ;  Poultices  786 

FAMILY  XIII. — PROTECTIVES  :  Adhesive  Plaster  ;  Lead  Plaster  ;  Soap  Plaster  ; 

Collodion  ;  Solution  of  Gutta-Percha 796 


xx  TABLE  OF  CONTENTS. 

DIVISION  II.— EXTRANEOUS  REMEDIES. 

PAGE 

FAMILY  I. — ANTACIDS  :  Sodium  and  its  Salts  ;  Lime,  its  Salts  and  Prepara- 
tions ;  Chalk,  or  Calcium  Carbonate ;  Calcium  Haloid  Salts 797 

FAMILY  II. — ANTHELM'NTICS  :   Pinkroot ;  Azedarach  ;  Wormseed  ;  Cusso  ; 
Santonica  ;  Santonin  ;  Male  Fern  ;  Pumpkin  Seed  ;  Turpentine  ;  Pome- 
granate Root  and  its  Alkaloids  ;  Thymol ;  Kamala  ;  Picric  Acid  ....      805 
FAMILY  III. — DIGESTANTS  :  Pepsin;  Pancreatin  ;  Extract  of  Malt;  Papain  .      815 

FAMILY  IV. — SLBSORBENTS  :  Charcoal,  Wood  and  Animal 819 

FAMILY  V. — DISINFECTANTS  :  Cold  and  Heat ;  Mercuric  Bichloride  ;  Binio- 
dide  of  Mercury  ;  Silver  Nitrate  ;  Chlorine  ;  Potassium  Permanganate ; 
Hydrogen  Dioxide  ;  Acetozone  ;  Phenol ;  Creosote  ;  Guaiacol ;  Salol ; 
Cresol ;  Naphtalin  ;  Naphtol ;  Betol ;  Menthol ;  Thymol ;  Thymacetin  ; 
Resorcin  ;  Formaldehyde  ;  Volatile  Oils  ;  Benzoin  ;  Benzoic  Acid  ;  Cin- 
namic  Acid  ;  Sulphurous  Acid  ;  Fluorides  ;  Boric  Acid  ;  Practical  Dis- 
infection    820 

APPENDIX. 

Apothecaries'  Measure  ;  Metrical  Weights  and  Measures  ;  Relations  of  Apothe- 
caries' and  Metrical  Weights  and  Measures — first,  to  each  other  ;  second, 
to  Cubic  Measure  ;  Table  of  the  Alcoholic  Strength  of  Distilled  Liquors, 
of  Wines,  and  of  Malt  Liquors  ;  Diagrams  of  Motor  Points 879 


THERAPEUTICS: 

ITS     PRINCIPLES     AND    PRACTICE, 


PART    I. 

REMEDIES,  REMEDIAL  MEASURES,  AND  REMEDIAL 
METHODS   WHICH   ARE   NOT   DRUGS. 


CHAPTER   I. 

GENERAL    CONSIDERATIONS — MASSAGE — FEEDING   OF    THE   SICK. 
GENERAL    CONSIDERATIONS. 

IN  the  treatment  of  chronic  disease  it  is  of  the  utmost  importance  that 
the  physician  inquire  minutely  into  the  personal  habits  of  the  patient  and 
insist  upon  their  regulation  in  accordance  with  the  needs  of  the  case. 
The  importance  of  the  alcoholic  habit  as  a  cause  of  local  and  constitu- 
tional disease  is  recognized  by  many  who  fail  to  perceive  as  clearly  the 
effects  of  the  excessive  use  of  other  stimulants.  Insomnia,  general  ner- 
vousness, and  various  cardiac  derangements  are  frequently  the  result  of 
the  tobacco-habit,  and  will  not  yield  to  any  treatment  until  the  abuse  is 
corrected.  Headache,  general  unrest,  nervousness,  and  many  other  symp- 
toms may  be  the  outcome  of  excessive  tea-  or  coffee-drinking,  and  espe- 
cially is  this  the  case  when  these  nerve-stimulants  are  employed  to  enable 
the  victim  to  continue  excessive  labor.  Among  the  lower  classes,  and 
pre-eminently  among  sewing-women,  the  nervines  just  mentioned  fre- 
quently replace  substantial  food,  and  the  resulting  headaches  and  nerve- 
failure  are  to  be  relieved  only  by  a  total  alteration  of  the  food-habits. 
The  physician  should  also  carefully  study  the  clothing  of  his  clientele  : 
especially  is  this  necessary  in  regard  to  young  children.  Some  mothers 
so  overload  the  child  as  to  keep  the  skin  in  a  condition  of  habitual  relaxa- 


2  MASSAGE. 

tion,  impeding  the  natural,  free  movements,  and  causing  general  over- 
heating. More  frequently,  however,  young  children  are  clothed  too  little 
than  too  much.  Bare  legs  and  bare  arms  in  cold  climates  are  fertile 
sources  of  illness.  There  cannot  be  two  opinions  in  regard  to  the  superi- 
ority of  wool  over  cotton  as  a  material  for  underclothing.  The  well-known 
effect  of  wet  clothing  in  causing  colds  is  due  to  the  rapidity  with  which  it 
conducts  heat  away  from  the  body.  Wet  cotton  is  almost  as  good  a  con- 
ductor of  heat  as  water  itself,  whereas  woollen  garments  when  wet  still 
resist  the  passage  of  heat.  During  exercise  cotton  underwear  becomes 
damp  with  perspiration,  and  in  the  subsequent  cooling  of  the  body  fails 
almost  entirely  as  a  protective,  whereas  a  woollen  shirt  under  similar  cir- 
cumstances maintains  the  temperature  of  the  vital  organs.  Modern  merino 
underclothing  is  essentially  cotton,  and  is  entirely  unfit  for  wear  by  deli- 
cate persons  in  cold  or  changeable  climates.  Persons  who  suffer  from 
frequent  catarrhs  or  are  of  a  rheumatic  or  gouty  diathesis,  or  whose  nutri- 
tion is  habitually  feeble,  should  always  wear  next  to  the  skin  either  wool 
or  silk.  When  the  question  of  expense  is  not  vital,  heavy  silk  under- 
garments are  as  serviceable  as  those  made  of  wool,  and,  indeed,  in  rheu- 
matic cases,  in  our  experience,  are  superior  to  woollen  underwear.  In 
very  many  persons,  and  especially  in  those  who  suffer  from  frequent  diar- 
rhoeas and  indigestions,  or  derangements  of  the  abdominal  viscera,  the 
abdominal  bandage  should  be  habitually  worn,  in  addition  to  the  ordinary 
underclothing.  It  should  be  sufficiently  wide  to  cover  the  whole  abdomen, 
should  be  either  of  silk  or  of  wool,  and  should  be  so  made  as  to  be  readily 
put  on  and  to  fit  closely  to  the  body.  A  simple  piece  of  flannel  of  suffi- 
cient size,  secured  in  its  place  by  means  of  ordinary  safety-pins,  makes, 
perhaps,  as  serviceable  an  abdominal  bandage  as  can  be  obtained.  Both 
abdominal  bandage  and  underclothing  should  be  worn  at  night,  although, 
for  purposes  of  cleanliness,  it  is  preferable  to  change  them  upon  going 
to  bed. 

The  physician  should  always  inquire  into  the  bathing-habits  of  the 
patient.  Cleanliness  and  the  maintenance  of  the  proper  condition  of  the 
skin  require  the  use  of  the  bath  at  least  twice  a  week.  In  some  very  deli- 
cate persons  the  general  bath  produces  marked  depression,  but  this  can 
almost  always  be  avoided  by  the  use  of  very  hot  water.  If  the  hot  or 
warm  bath  be  employed  habitually,  it  should  be  preferably  taken  at  night, 
and,  unless  under  very  exceptional  circumstances,  the  hot  bath  should 
always  be  immediately  followed  by  cold  sponging  or  the  cold  shower- 
bath,  or  by  a  plunge  into  cold  water. 

MASSAGE. 

The  term  massage  is  used  as  the  generic  name  for  external  manipula- 
tions which  are  employed  for  the  purpose  of  affecting  the  nervous  and 
muscular  systems  and  the  general  circulation.  From  time  immemorial 
such  procedures  have  been  used  upon  both  man  and  domestic  animals. 
In  the  sick-room,  in  the  arena,  upon  the  race-course,  and  in  the  luxurious 


MASSAGE.  3 

pursuit  of  health  their  usefulness  has  been  abundantly  proved  by  the 
ancient  Greeks  and  Romans,  by  modern  civilized  nations,  and  by  barbar- 
ous or  semi-barbarous  people.  As  remedial  measures  they  were  spoken 
of  in  the  writings  of  the  Chinese  three  thousand  years  before  the  Christian 
era,  and  were  fully  recognized  by  Hippocrates  and  Celsus. 

Massage  is  not  rubbing  of  the  skin,  although  it  has  in  all  probability 
grown  out  of  the  practice  of  such  rubbing.  General  massage  is  practised 
to  affect  the  general  condition  of  the  body.  Local  massage  is  for  the 
relief  of  local  affections. 

The  methods  of  massage  are  so  complicated  that  their  discussion 
requires  more  space  than  can  be  here  spared  for  them.  Moreover,  they 
can  scarcely  be  learned  even  from  the  largest  volume  treating  solely  upon 
the  subject,  but  must  be  acquired  by  practice  under  the  guidance  of  a 
person  having  the  necessary  technical  knowledge.  A  masseur  must  have 
sufficient  knowledge  of  anatomy  to  understand  the  general  drift  of  the 
circulation  and  the  positions  and  shapes  of  the  muscles  and  of  the  muscle- 
masses,  must  be  cleanly  and  agreeable  in  person,  and  must  be  possessed 
of  the  proper  technical  skill.  Especially  is  this  true  when  the  attempt  is 
to  treat  local  disease.  Under  such  circumstances  a  really  accurate  knowl- 
edge of  the  shapes  and  positions  of  muscles,  tendons,  joint  surfaces,  and 
other  portions  of  the  affected  limb  is  essential.  Unless  under  very  peculiar 
circumstances,  the  sex  of  the  operator  should  be  that  of  the  patient. 

Massage  is  usually  practised  upon  the  bared  skin,  and  we  think  that  this 
is  preferable,  although  we  have  known  skilful  and  successful  manipulators 
who  preferred  that  the  patient  should  have  thin,  tight-fitting  underclothes. 
The  question  as  to  whether  the  skin  should  be  anointed  before  massage  is 
one  concerning  which  practice  differs.  The  object  of  massage  is  to  affect, 
not  the  skin,  but  the  underlying  tissue,  and  when  there  is  special  sensitive- 
ness or  irritability  of  the  skin  there  can  be  little  doubt  as  to  the  imperative 
necessity  of  some  ointment.  Vaseline  may  be  employed.  A  very  excel- 
lent material  is  pure  and  fresh  cocoa-nut  oil.  Only  so  much  of  the  grease 
should  be  used  as  is  necessary  to  render  the  skin  soft  and  pliable  and  to 
enable  the  fingers  to  glide  easily  over  it. 

Without  entering  into  any  detailed  discussion  of  the  physiological 
action  of  massage,  it  is  sufficient  to  point  out  that  general  massage  acts 
very  much  like  general  exercise,  without  the  attendant  expenditure  of 
nerve  and  muscular  force  on  the  part  of  the  patient. 

During  prolonged  muscular  inaction,  whether  from  indolence,  disease, 
feebleness,  or  other  cause,  the  muscular  structure  itself  suffers  some  degra- 
dation and  the  peripheral  circulation  becomes  very  feeble.  Much  of  the 
albuminous  liquid  which  escapes  from  the  blood-vessels  and  diffuses  itself 
through  the  tissues,  after  serving  the  purposes  of  nutrition,  is  taken  up 
by  the  lymphatic  system  and  returned  to  the  great  blood-vessels.  If  there 
be  any  vis  a  tergo  driving  this  liquid  from  the  periphery  to  the  centre,  it 
is  so  feeble  that  the  return  of  the  juices  depends  chiefly  upon  the  squeezing 
of  the  various  juice-channels  during  muscular  contractions.  During  ha- 


4  MASSAGE. 

bitual  inactivity  the  movement  of  fluids  in  the  lymph-channels  outside  of 
the  blood-vessels  is  excessively  sluggish,  and  it  is  one  great  object  of  the 
stroking  movements  in  massage  to  force  these  juices  onward  ;  it  is  for  this 
reason  that  these  movements  are  directed  from  the  periphery  towards  the 
centre.  It  is  not  probable  that  the  whole  effect  of  the  stroking  is  me- 
chanical. The  influence  of  peripheral  nervous  irritations  upon  internal 
organs  and  upon  the  general  circulation  is  recognized  by  almost  every 
one,  and  every  invalid  knows  the  power  of  soothing  strokes  and  touches 
in  relieving  nervousness  and  even  pain.  General  stroking  movements,  if 
properly  administered,  are  to  most  persons  very  quieting,  and  not  rarely, 
when  opportunity  is  afforded,  general  massage  is  followed  by  quiet  sleep. 

The  kneading  and  percussion  movements  of  massage  act  chiefly  upon 
the  local  circulation,  increasing  its  activity  in  the  same  way  that  spank- 
ing causes  a  blush  upon  the  young.  Kneading  performs,  however,  still 
another  function.  Under  certain  circumstances  the  fibres  of  muscles  within 
their  sheaths  or  the  neighboring  individual  muscles  through  their  sheaths 
become  agglutinated,  and  even  the  skin  itself  may  get  to  be  abnormally 
tense  and  attached  to  the  subdermal  tissue, — a  condition  which,  when  it 
occurs  in  the  lower  animals,  is  known  as  "  hide- bound."  Moreover, 
gouty  or  inflammatory  exudations  may  form  in  almost  any  portion  of  the 
body.  Kneading  especially  has  power  to  mechanically  loosen  aggluti- 
nated fibres,  to  break  up  masses  of  exudation,  and  to  so  stimulate  the 
local  circulation  in  deeply  seated  tissues  as  to  cause  exudations  to  disap- 
pear or  even  glandular  and  lymphatic  enlargements  to  be  reduced. 

General  massage  is  employed  advantageously  in  various  neurasthenic 
conditions,  and  forms  an  important  part  of  the  system  of  treatment  known 
as  the  Rest-Cure  (see  page  17).  When  there  is  marked  feebleness  or 
nervousness,  massage  should  at  first  be  practised  very  gently,  but,  except 
in  rare  cases,  it  will  soon  be  found  grateful  to  the  patient.  During  the 
processes  of  the  rest-cure,  both  massage  and  the  faradic  current  will  fre- 
quently reveal  the  existence  of  unsuspected  spots  of  tenderness  in  various 
parts  of  the  body.  Such  tenderness  marks  local  congestion,  or  very 
often  gouty  exudation,  and  the  best  results  follow  from  the  gradual  but 
persistent  application,  day  after  day,  of  increasingly  powerful  massage, 
often  aided  by  very  rapidly  interrupted  faradic  currents,  to  the  centres  of 
tenderness,  which  almost  invariably  disappear  sooner  or  later.  Closely 
allied  to  these  sore  spots  is  the  tenderness  of  the  so-called  spinal  irritation, 
or  spinal  anaemia.  When  this  spinal  tenderness  is  pronounced,  great  care 
is  necessary  in  the  gradual  application  of  massage  and  the  faradic  current 
to  the  affected  region.  If  the  operator  be  sufficiently  careful  at  first  to 
work  only  upon  the  borders  of  the  tenderness,  and  gradually  to  approach 
the  centre,  excellent  results  can  usually  be  obtained.  Under  these  cir- 
cumstances massage  is  useful  not  only  as  part  of  the  general  plan  of 
treating  the  constitutional  condition,  but  also  by  its  local  power  in  dis- 
persing congestions  and  allaying  nervous  irritations. 

The  first  seance  in  general  massage  should  not  last  longer  than  half  an 


MASSAGE.  5 

hour,  but  in  a  little  time  a  full  hour  will  be  required.  When  there  is  lack 
of  digestive  power,  constipation,  or  any  similar  symptom, — the  outcome 
of  sluggishness  of  the  abdominal  circulation  and  nerve-supply, — local 
massage  of  the  abdominal  and  pelvic  regions  should  be  freely  employed. 

Abdominal  massage  for  the  purpose  of  affecting  circulation  in  the 
intestines  should  be  performed  as  follows.  For  one  or  two  moments  the 
abdominal  muscles  themselves  should  be  kneaded,  the  individual  move- 
ments being  transversely  directed  across  the  muscle-fibres  ;  next,  in  order 
to  influence  the  small  intestines,  a  series  of  circular  sweeping  strokes 
should  be  made  around  the  umbilicus,  one  hand  following  the  other  rap- 
idly so  as  to  complete  the  circles,  firm  pressure  being  instituted  with  the 
outer  portion  of  the  palms  ;  then  kneading  movement  should  be  per- 
formed, beginning  at  the  region  of  the  ileo-caecal  valve,  each  movement 
being  transverse  to  the  course  of  the  large  intestine,  the  series  of  move- 
ments following  the  large  intestine  upward  to  the  hypochondriac  region, 
then  transversely,  and  finally  downward  along  the  whole  course  of  the 
colon.  In  some  cases,  especially  when  there  is  enlargement  of  the  liver 
with  torpor,  good  is  to  be  achieved  by  kneading  movements  directly  over 
and  upon  the  diseased  organ.  When  along  with  the  enlargement  of  an 
abdominal  viscus  there  is  a  condition  of  softness,  great  care  should  be  ex- 
ercised not  to  injure  the  organ  by  too  firm  pressure.  This  applies  espe- 
cially to  the  pulpy  condition  of  the  spleen  sometimes  seen  in  malarial 
disease. 

Local  massage  is  of  great  value  in  the  treatment  of  sprains,  chronic 
inflammations  of  the  joints,  and  various  other  surgical  affections,  but 
should  rarely  be  practised  when  the  symptoms  of  the  inflammation  are  at 
all  acute.  In  subacute  or  chronic  rheumatism  affecting  muscular  or  fibrous 
tissue  it  is  of  great  value,  especially  when  combined  with  judicious  passive 
movements.  Under  its  practice  adhesions  are  broken  up,  exudations  are 
dispersed  and  finally  absorbed,  and  the  natural  condition  of  the  parts  re- 
stored. 

In  various  forms  of  paralysis  local  massage  is  very  useful  in  main- 
taining muscular  nutrition.  When  the  nerve-lesion  is  in  the  cerebrum, 
the  muscles  do  not  suffer  in  their  nutrition,  except  secondarily  from  in- 
activity, and  massage  is  usually  not  required  in  the  early  weeks  of  the 
affection.  After  a  stroke  of  hemiplegia  it  is  rarely  proper  to  begin  massage 
for  two  or  three  weeks  ;  but  whenever  the  temperature  of  the  arm  de- 
cidedly and  permanently  falls,  or  serous  exudation  into  the  cellular  tissue 
marks  a  loss  of  vascular  tone,  or  when  evidences  of  returning  control  over 
the  muscles  are  manifest,  local  massage  is  often  of  service.  At  first  the 
stance  should  not  last  more  than  five  minutes,  but  after  a  time  it  may 
continue  for  ten  or  even  fifteen  minutes.  In  those  forms  of  palsy,  such  as 
infantile  paralysis,  in  which  the  trophic  centres  in  the  spinal  cord  are 
especially  implicated,  massage  is  of  great  importance.  In  acute  cases  it 
should  be  commenced  as  soon  as  the  subsidence  of  fever  and  other  symp- 
toms of  constitutional  irritation  marks  the  passage  of  the  first  stage  of 


6  FEEDING  OF   THE   SICK. 

activity  in  the  spinal  lesion.  When  the  infantile  paralysis  develops  grad- 
ually, massage  may  be  employed  as  soon  as  the  paralysis  is  recognized. 
It  does  not  directly  influence,  to  any  extent,  the  fundamental  spinal  lesion, 
but,  by  maintaining  a  healthy  condition  of  the  peripheral  apparatus,  is  of 
the  greatest  service  in  those  cases  in  which  there  is  a  tendency  to  more  or 
less  complete  repair  of  the  structure  of  the  spinal  cord.  In  various  local 
paralyses,  as  from  pressure,  from  rheumatic  affections  of  the  nerves,  or 
from  other  temporary  or  removable  conditions  of  nervous  or  muscular 
tissue,  massage  may  do  much  good.  When  the  loss  of  power  in  a  muscle 
is  due  to  direct  violence,  as  occurs  with  especial  frequency  in  the  deltoid 
muscle  from  falls  on  the  shoulder,  massage  should  be  assiduously  em- 
ployed as  soon  as  the  primary  inflammation  produced  by  the  injury  has 
subsided.  In  such  cases  the  treatment  is  of  especial  advantage  in  dis- 
persing exudations  and  restoring  the  muscles  and  the  muscle-fibre  bundles 
to  their  normal  relations  and  their  normal  looseness. 

FEEDING    OF    THE    SICK. 

The  present  article  is  not  a  treatise  upon  diet  or  dietetics  ;  the  books 
upon  this  subject  are  sufficiently  numerous,  but  their  scope  is  often  too 
wide  for  the  needs  of  the  medical  practitioner.  In  elaborate  discussions 
upon  the  contained  percentage  of  nitrogen  and  general  food- qualities  of 
various  articles  of  diet,  upon  the  cost  and  commercial  history  of  foods, 
upon  the  amount  of  food  necessary  to  sustain  life,  and  upon  the  most 
economical  forms  of  military,  prison,  and  hospital  rations,  etc. ,  the  con- 
sideration of  the  feeding  of  the  sick  in  private  practice  is  often  so  over- 
whelmed as  to  be  lost  entirely.  We  propose  to  give  here  a  brief  practical 
summary  of  the  methods  of  feeding  in  sickness  when  pecuniary  consider- 
ations are  of  secondary  importance. 

The  proper  feeding  in  acute  diseases  accompanied  by  high  fever 
varies  to  some  extent  according  to  the  individual  affection,  but  is  subject 
to  general  principles  which  are  sufficient  practical  guides  for  most  cases. 
All  such  acute  diseases  are  for  present  purposes  readily  divided  into  those 
in  which  the  acute  febrile  stage  is  very  short  and  those  in  which  it  is  pro- 
longed. When  the  acute  febrile  stage  is  very  severe  and  temporary,  it  is 
usually  associated  with  a  complete  anorexia,  which  the  practitioner  may 
obey  with  safety.  In  the  first  day  or  two  of  the  onset  of  an  acute  pneu- 
monia, violent  scarlet  fever,  or  similar  affections,  there  is  no  cause  for 
alarm  even  if  the  patient  take  no  food.  The  digestive  power  at  this  time 
may  be  in  complete  abeyance.  After,  however,  the  first  day  or  two  of 
such  an  attack,  and  whenever  the  febrile  reaction  is  prolonged,  a  loss  of 
appetite  amounting  even  to  a  disgust  with  food  is  no  excuse  for  abstinence. 
All  such  states,  with  their  accompanying  diseases,  tend  to  fatal  result 
through  exhaustion,  and  much  can  be  done  by  proper  feeding  to  prevent 
complete  failure  of  vital  power.  The  older  writers  upon  dietetics  taught 
that  a  fever  patient  was  not  to  be  fed,  and  some  modern  authors  reiterate 
the  old  dictum.  Fever  is  not,  however,  any  centra-indication  to  food. 


FEEDING   OF  THE   SICK.  7 

It  is,  indeed,  usually  associated  with  loss  of  digestive  power,  and  if  under 
such  circumstances  the  stomach  be  overloaded  with  coarse  food  the  symp- 
toms will  be  aggravated  by  the  resulting  acute  indigestion.  The  amount 
of  nourishment  received  by  a  body  is  measured,  not  by  the  amount  of  food 
put  into  the  stomach,  but  by  the  amount  which  is  assimilated  ;  and  in 
febrile  complaints  the  effort  of  the  physician  must  be  directed,  not  to  the 
filling  of  the  stomach,  but  to  the  obtaining  of  as  large  an  assimilation  of 
food  as  is  possible  without  disturbing  the  alimentary  canal.  Any  symp- 
toms of  gastric  or  intestinal  disturbance  should  be  the  signal  for  the  imme- 
diate lessening  of  the  food.  Such  gross  manifestations  as  vomiting,  sour 
or  nauseous  eructations,  and  gastric  distress  are  perceived  at  once  by  the 
most  careless  ;  but  in  typhoid  fever  we  have  seen  skilful  practitioners  over- 
look the  real  cause  of  an  excessive  tympany  or  an  increased  diarrhoea, 
and  continue  the  overfeeding  while  attempting  to  relieve  these  symptoms 
by  medicine.  Such  practice  is  exceedingly  reprehensible.  In  febrile 
adynamic  diseases  the  feeding  should  be  at  short  intervals,  with  small 
amounts  of  liquid  food  of  a  nutritious,  easily  digested  character,  and  our 
own  experience  leads  us  more  and  more  to  the  habitual  use  of  foods 
which  have  been  partially  digested  artificially. 

The  question  of  night-feeding  in  severe  cases  is  an  important  one. 
Our  belief  is  that  death  occurs  much  more  frequently  in  adynamic  diseases 
between  one  and  five  o'clock  in  the  morning  than  at  any  other  time, — a 
circumstance  largely  attributable  to  the  habitual  withholding  of  food  and 
stimulants  during  the  night.  Sleep  is  essential  to  the  recuperation  of  vital 
force,  but  an  exhausted  patient  usually  goes  to  sleep  readily  after  the  par- 
tial awakening  which  is  sufficient  for  the  administration  of  a  milk  punch, 
or  else  sleeps  in  so  broken  a  manner  that  the  careful  nurse  can  give  the 
food  at  short  intervals  without  awakening  him.  In  no  typhoid  case  of 
severe  type  should  an  interval  of  more  than  three  hours  be  allowed  to 
elapse  at  night  without  food  and  stimulants,  and  the  amount  given  at  a 
single  time  should  be  so  increased  that  almost  as  much  will  be  taken  during 
the  night  as  during  the  day. 

In  typhoid  cases  alcohol  in  some  form  should  be  given  with  the  food, 
in  not  too  large  proportion.  Alcoholic  liquors  in  moderate  amount  stim- 
ulate the  stomach  and  aid  digestion  and  absorption,  but  in  large  amount 
interfere  with  these  processes.  It  may  be  set  down  as  a  general  rule  with 
few  exceptions  that  all  foods  given  in  protracted  febrile  states  should  be  in 
liquid  form. 

Liquid  foods  may  be  divided  into  Liquid  Meat  Foods,  Milk  Foods, 
and  Artificially  Digested  Foods. 

LIQUID  MEAT  FOODS. — It  must  be  remembered  that  all  articles  of 
the  present  class  are  stimulants  rather  than  nutrients.  Most  of  them  do 
not  contain  more  than  one  per  cent,  of  albuminous  substances.  Under 
this  heading  we  include  all  liquid  preparations  of  meat  made  without  arti- 
ficial digestion. 

At  one  time  these  liquid  preparations  of  meat  were  supposed  to  repre- 


8  FEEDING   OF   THE   SICK. 

sent  the  whole  nutritive  value  of  the  meat,  but  recently  all  nutritive  power 
has  been  denied  to  them.  They  contain  kreatin,  kreatinin,  sarkosin,  sar- 
kin,  xanthin,  kreanin,  inosite,  fat,  and  inorganic  salts,  with  a  very  small 
amount  of  albuminous  principles.  It  is  not  probable  that  any  of  these 
substances,  except  the  albumin  and  the  fat,  are  capable  of  being  assim- 
ilated and  used  as  food.  The  experiments  of  Kemmerich  also  indicate 
very  strongly  that  they  are  not  nutrients,  for  he  found  that  animals  fed 
exclusively  upon  these  preparations  died  even  more  quickly  than  those 
left  to  starve.  There  can  be  no  doubt  that  death  under  these  circum- 
stances was  largely  due  to  the  depressing  effect  of  the  inorganic  salts  con- 
tained in  the  extracts.  Clinical  experience,  in  a  measure,  conforms  with 
this  scientific  reasoning.  At  a  time  when  beef  essence  and  beef  tea  were 
very  largely  relied  upon  as  nutrients  in  Philadelphia,  it  was  found  that 
they  acted  better  when  milk  was  also  given.  In  his  earlier  trips  into  the 
wilderness,  involving  much  physical  labor,  H.  C.  Wood  took  with  him 
the  best  artificial  meat  extracts  to  serve  as  condensed  food,  but,  after  a 
few  trials,  found  that  they  were  unable  to  sustain  prolonged  effort, — as  the 
guides  put  it,  "  they  do  not  stick  to  a  man's  ribs," — and,  although  at 
that  time  the  theory  was  that  they  were  concentrated  nourishment,  practi- 
cal experience  soon  led  to  their  abandonment.  Although  of  little  use  as 
food,  these  substances  are  valuable  stimulants,  and  may  by  reviving 
temporarily  an  exhausted  patient  prepare  the  way  for  the  digestion 
of  food.  In  a  series  of  experiments  made  upon  the  frog's  heart  by 
Thomas  J.  Mays  (Therap.  Gaz.,  vol.  ii.  p.  152),  it  was  found  that  (the 
artificial  beef  extracts  and  concentrated  beef  preparations  had  a  very  de- 
cided influence  in  maintaining  the  activity  of  the  systoles.  Notwith- 
standing Mays' s  arguments  to  the  contrary,  however,  we  believe  that  the 
effect  of  beef  extracts  upon  the  frog's  heart  is  entirely  similar  to  that  of 
the  phosphate  of  calcium  (see  CALCII  PHOSPHAS).  In  typhoid  and  other 
similar  low  fevers  it  is  an  excellent  plan  to  give  beef  essence  or  beef  tea 
alternate  hours  with  milk  punch.  During  convalescence  a  hot  bowl  of 
beef  tea  or  beef  essence  after  exertion  such  as  carriage-riding,  walking, 
etc. ,  may  act  very  well  as  a  stimulant.  By  the  addition  of  various  sub- 
stances these  liquid  preparations  of  meat  can  be  made  nutritive  :  thus,  an 
egg  rapidly  stirred  into  a  bowl  of  beef  essence  forms  a  very  useful  stimu- 
lating food.  There  are  in  the  market  various  extracts  of  beef  claiming  to 
represent,  in  a  solid  form,  beef  essence.  The  better  forms  of  these  articles 
undoubtedly  do  represent  in  great  part  beef  essence,  but  they  are  dis- 
tinctly inferior  to  the  freshly  made  preparation  in  taste,  and  in  containing 
no  albumin  :  so  that  it  is  always  better  to  employ  the  fresh  beef  essence 
if  it  can  be  procured. 

Liquid  meat  foods  are  divisible  into  those  that  are  raw  and  those  that 
are  cooked.  Of  the  raw  foods  of  the  class,  the  best  is  meat  juice.  This 
is  made,  according  to  the  directions  of  Pettenkofer  and  Voit,  by  selecting 
lean  meat  from  the  round  of  beef,  cutting  it  into  small  pieces,  and  ex- 
pressing the  juice  in  a  press  of  sufficient  power, — such  as  now  can  be  pur- 


FEEDING   OF   THE   SICK.  9 

chased  at  any  of  the  larger  drug-stores.  This  juice  contains,  in  addition 
to  the  salts  and  extractives,  the  albumin  that  remains  fluid  after  the  rigor 
mortis, — chiefly  serum-albumin  and  coloring  matters.  The  proportion 
of  albumin  is  about  six  per  cent. :  by  heating  the  albumin  is  precipitated, 
but  it  is  not  affected  by  salt  or  by  mere  warming. 

Meat  juice  is  a  valuable  preparation  when  a  powerful  stimulation  is 
desired  and  the  digestive  forces  are  exceedingly  weak,  as  in  the  feebleness 
or  collapse  that  follows  cholera  infantum  and  other  infantile  diarrhoeas. 
Its  taste  is  that  of  raw  meat,  and  is  so  disagreeable  to  many  persons  as  to 
prevent  its  use. 

Liebig's  beef  tea  is  made  by  adding  seven  ounces  of  water  and  three  or  four 
drops  of  hydrochloric  acid  to  one  and  a  half  pounds  of  lean  beef,  allowing  to  stand 
one  hour,  passing  through  a  hair  sieve,  and  washing  out  the  meat  with  three  ounces, 
of  water.  This  infusion  contains,  on  the  average,  not  more  than  one  per  cent,  of 
albumin.  The  hydrochloric  acid  added  to  the  water  is  not  sufficient  to  dissolve 
the  myosin  of  the  muscle  :  so  that  this  preparation  can  be  looked  upon  as  nothing 
more  than  a  dilution  of  meat  juice,  and  is  very  inferior.  To  have  any  effect  it  must 
be  given  in  enormous  quantities. 

The  cooked  concentrated  liquid  forms  of  meat  extracts  are  beef  tea 
and  beef  essence.  Neither  of  these  can  be  considered  to  have  distinct 
nutritive  value.  It  is  very  rare  for  them  to  contain  more  than  one  per 
cent,  of  albuminous  substances;  but  they  are  powerful  stimulants,  and  for 
such  purposes  are  as  useful  as  the  expressed  meat  juice. 

To  make  beef  tea,  cut  one  pound  of  round  of  beef  into  small  cubes  not  larger 
than  half  an  inch  in  diameter;  soak  for  two  hours  on  the  back  of  the  range,  in  an 
earthenware  pipkin,  with  one  pint  of  cold  water,  and  allow  to  simmer  for  about 
fifteen  minutes,  and  finally  to  boil  for  three  minutes;  add  half  a  teaspoonful  of  salt 
and  pepper,  pro  re  nata. 

To  make  beef  essence,  prepare  the  meat  as  for  beef  tea  ;  put  it  into  an  earthen- 
ware bottle  without  water  and  loosely  cork  ;  set  this  in  a  pot  of  cold  water  and 
bring  very  gradually  to  the  boiling  point  ;  boil  for  twenty  minutes  or  half  an  hour. 

Soups  are  liquid  preparations  which  resemble  beef  tea  and  beef  essence 
in  containing  the  extractives  of  meat,  but  which  differ  from  these  prepara- 
tions in  having  in  them  various  nutritive  substances.  Soup  is  therefore 
both  a  stimulant  and  a  nutrient,  the  amount  of  nutrient  material  varying 
greatly  according  to  the  preparation  of  the  soup.  The  lighter  forms  of 
soups  are  commonly  spoken  of  as  broths.  They  may  be  used  when  the 
stomach  rejects  less  readily  digested  forms  of  food. 

To  make  chicken  broth,  take  three  pounds  of  chicken  well  cleaned,  cover  with 
cold  water,  boil  from  three  to  five  hours  (until  the  meat  falls  to  pieces),  strain, 
cool,  and  skim  off  the  fat.  To  a  pint  of  this  add  salt  and  pepper  and  two  table- 
spoonfuls  of  soft  rice  which  has  been  previously  thoroughly  boiled  in  salt  water ; 
bring  the  broth  to  a  boil.  In  preparing  the  rice,  half  a  cupful  should  be  boiled  for 
thirty  minutes  with  a  teaspoonful  of  salt  in  a  pint  of  water.  To  make  mutton  broth, 
take  one  pound  of  lean,  juicy  mutton,  chopped  fine,  and  proceed  as  with  chicken 
broth. 


io  FEEDING   OF   THE   SICK. 

In  the  preparation  of  soups  the  first  thing  is  the  making  of  the  so- 
called  stock,  or  basis  for  the  soup.  There  are  two  distinct  stocks  :  one 
which  may  be  known  as  the  brown  stock,  the  other  as  clear  stock  or  con- 
somme. 

To  make  brown  stock,  take  four  pounds  of  shin  of  beef,  four  quarts  of  cold 
water,  ten  whole  cloves,  four  peppercorns,  a  bouquet  of  herbs  (sweet  marjoram, 
summer  savory,  thyme,  and  sage),  one  tablespoonful  of  salt,  three  small  onions, 
one  turnip,  one  carrot,  two  stalks  of  celery,  two  sprigs  of  parsley.  Cut  the  meat 
from  the  bones,  after  which  place  the  bones  and  one-half  of  the  meat  in  a  soup- 
kettle  and  allow  to  stand  for  half  an  hour  in  the  cold  water.  Heat  gradually, 
and  allow  to  simmer  for  six  or  seven  hours.  Brown  the  remainder  of  the  meat  in 
two  tablespoonfuls  of  beef-drippings,  and  add  with  the  other  meat  and  with  the 
vegetables  chopped  fine,  when  the  kettle  is  put  on  the  fire  to  simmer.  After  it  has 
simmered  the  required  time,  strain  the  stock  and  set  aside  to  cool,  the  fat  being 
removed  from  the  top.  The  stock  is  then  ready  for  use. 

To  make  consomme  or  clear  stock,  proceed  in  exactly  the  same  way  as  for 
brown  stock,  except  that  three  pounds  of  the  knuckle  of  veal  are  to  be  added  to 
the  meat,  and  all  the  meat  is  to  be  put  in  at  once  without  browning.  After  the 
stock  has  been  formed,  in  order  to  clear  it  add  the  white  and  the  shell  of  one  egg 
and  the  juice  and  rind  of  one  lemon,  beating  them  all  up  together  ;  then  put  on  the 
fire,  bring  to  the  boiling  point,  strain  through  a  sieve,  and  again  through  a  napkin, 
without  pressure  or  squeezing,  and  serve. 

In  making  the  soups  the  stocks  must  never  be  allowed  to  boil,  or  at 
most  must  be  brought  only  for  a  moment  to  the  boiling  point. 

To  make  Julienne  soup,  put  one  pint  of  the  brown  stock  on  the  fire  to  heat, 
after  which  a  pint  of  finely  chopped  vegetables  (turnip,  carrot,  etc. ) ,  with  half  a  tea- 
spoonful  of  salt,  should  be  put  on  with  a  little  water  to  parboil.  This  being  done, 
add  the  vegetables  to  the  stock,  and  season  with  half  a  saltspoonful  of  pepper. 
Vermicelli  soup  is  made  by  adding  half  a  cup  of  vermicelli  to  a  pint  of  the  brown 
stock.  Cook  the  vermicelli  for  ten  minutes  in  salted  boiling  water,  season  with  a 
half-teaspoonful  of  salt  and  a  half-saltspoonful  of  pepper,  and  add  to  the  warm 
stock. 

A  very  elegant  stimulating  and  nutritious  soup  can  be  made  out  of 
consomme  by  boiling  ordinary  pearl  sago  in  salt  water  for  from  two  to 
three  hours,  until  the  grains  become  swollen  almost  to  bursting,  and  then 
stirring  the  sago  into  the  consomme  while  still  boiling. 

MILK  FOODS. — Of  all  liquid  foods  milk  is  the  best  and  the  most  gen- 
erally applicable  to  the  treatment  of  disease.  Cow's  milk  contains,  in 
round  numbers,  87.5  parts  of  water,  3  parts  of  casein,  0.75  part  of  albu- 
min, 3.6  parts  of  fat,  5  parts  of  sugar,  and  0.07  part  of  inorganic  salts. 
One  pint  of  milk  contains,  in  round  numbers,  0.6  ounce  of  solid  albumi- 
nous substance,  o.  6  ounce  of  fat,  and  o.  8  ounce  of  sugar.  When  two  quarts 
of  milk  are  taken  in  the  course  of  twenty-four  hours,  about  two  and  a  half 
ounces  of  fat  are  ingested, — an  amount  too  great  for  an  inefficient  ali- 
mentary canal  to  digest,  so  that  it  is  often  necessary  to  skim  the  milk.  As 
milk  contains  practically  no  indigestible  residue,  it  leaves  behind  it  in  the 
alimentary  canal  no  fecal  matter,  and  its  use  therefore  frequently  pro- 


FEEDING   OF  THE   SICK.  n 

duces  constipation.  In  cases  of  diarrhoea  this  tendency  to  a  binding  action 
can  be  increased  by  boiling  the  milk,  a  process  which  coagulates  the  albu- 
min of  the  milk  and  slightly  lessens,  if  the  scum  be  removed,  its  nutritive 
value.  When  milk  is  used  very  freely  and  the  digestion  is  feeble,  there  is 
always  danger  of  the  formation  in  the  stomach  of  a  coagulum  so  dense  that 
the  gastric  juice  will  not  be  able  freely  to  penetrate  it.  This  difficulty  can 
usually  be  overcome  by  a  little  care.  The  addition  of  from  half  an  ounce 
to  an  ounce  of  lime-water  to  every  five  or  six  ounces  of  milk  has  a  distinct 
tendency  to  prevent  too  rapid  and  firm  coagulation.  Sipping  milk  instead 
of  drinking  it — in  other  words,  putting  the  milk  in  the  stomach  in  small 
quantities  at  a  time — has  a  still  greater  power  in  repressing  the  formation 
of  hard  coagulum.  When  the  digestive  powers  are  feeble,  milk  should 
be  taken  slowly  in  small  quantities  at  a  time.  In  some  cases  it  is  very 
important  that  it  be  drunk  hot,  but  without  previous  boiling. 

There  are  various  useful  nutrient  and  stimulant  foods  prepared  with 
alcohol  in  milk,  as  follows  : 

To  make  wine  whey,  bring  half  a  pint  of  milk  to  the  boiling  point ;  add  half  a 
pint  of  sherry  wine,  and  allow  to  stand  in  a  warm  place  for  five  minutes  ;  strain, 
and  sweeten  to  taste.  The  whey  which  is  left  consists  almost  exclusively  of  wine 
and  water,  with  milk  sugar  and  milk  salts.  It  contains  very  little  nutriment,  but 
is  sometimes  tolerated  by  the  stomach  which  refuses  other  food. 

To  make  milk  punch,  take  half  a  pint  of  milk  ;  pour  into  it  from  a  dessertspoon- 
ful to  a  tablespoonful  of  brandy,  rum,  or  whiskey,  according  to  the  needs  of  the 
patient ;  sweeten  and  spice  with  nutmeg  to  taste.  This  preparation  represents  all 
the  nutritive  value  of  milk  and  the  stimulating  effects  of  the  liquor.  If  the  stomach 
be  at  all  delicate,  a  tablespoonful  of  lime-water  should  always  be  added  to  it  before 
putting  in  the  brandy. 

To  make  eggnog.  Eggnog  is  a  heavy,  rich,  highly  nutritive  liquid,  which  must 
be  employed  in  limited  quantities,  and  very  carefully  when  there  is  any  delicacy  of 
stomach.  The  yolk  of  one  egg  may  be  added  to  half  a  pint  of  milk,  afterwards 
from  half  an  ounce  to  an  ounce  of  brandy,  and  the  white  then  beaten  in. 

Sometimes  when  the  stomach  rejects  almost  all  forms  of  food,  the 
addition  of  carbonic  acid  water  to  the  milk  meets  with  success.  Equal 
quantities  should  be  employed,  and  the  casein  of  milk  should  be  coagu- 
lated in  fine  flakes.  A  light,  powerfully  stimulant  beverage,  somewhat 
similar  to  the  one  just  mentioned,  but  to  some  palates  more  elegant,  is 
made  by  the  addition  of  champagne  to  milk. 

There  are  certain  forms  of  fermented  milk  which  are  valuable  as  being 
easily  digested  by  the  stomach  and  very  acceptable  to  the  palate.  They 
also  render  possible  some  variety  of  food  to  persons  largely  restricted  to 
milk  diet. 

Koumiss,  or  kumys,  is  a  fermented  liquid  prepared  by  the  Tartars  from  mares' 
milk.  In  this  country  it  is  made  from  cows'  milk  :  it  is  to  most  persons  a  very 
agreeable  beverage,  which  in  nutritive  qualities  represents  the  same  quantity  of 
milk,  and  is  by  most  stomachs  much  more  easily  digested.  It  is  very  well  suited 
for  the  treatment  of  convalescence  and  of  chronic  diseases,  though  it  may  be  used, 
often  with  great  advantage,  in  acute  febrile  illnesses.  Take  an  ordinary  beer-bottle 


12  FEEDING   OF   THE   SICK. 

with  a  patent  shifting  cork,  put  in  it  one  tablespoonful  of  white  sugar,  one  pint  of 
milk,  one-sixth  of  a  cake  of  Fleischmann's  yeast  or  one  drachm  of  strong  liquid 
yeast,  shake  well,  allow  to  stand  from  eight  to  ten  hours  in  a  temperature  of  from 
85°  to  95°  F.,  shake  well,  and  put  upon  the  ice  to  cool.  This  ought  to  be  used 
within  twenty-four  hours  after  being  made.  The  longer  the  fermentation  is  allowed 
to  continue  the  more  sour  is  the  koumiss  ;  and  its  condition  should  be  regulated  to 
suit  the  individual  palate  and  stomach  of  the  patient.  If  it  be  desired,  it  may  be 
flavored  by  the  addition  of  a  small  piece  of  vanilla  bean  to  the  milk  before  fermen- 
tation. 

Matzoon  differs  from  koumiss  in  that  it  contains  no  carbonic  acid,  is  thicker, 
and  more  cheesy  in  its  flavor.  It  occurs  in  the  market  in  various  brands,  but  we 
know  of  no  practical  method  of  making  it  at  home.  It  is  the  product  of  a  peculiar 
fungus  known  as  the  kefir  ferment. 

Milk  may  be  used  as  the  basis  of  a  number  of  farinaceous  or  starchy 
liquids.  It  must  be  remembered  that  these  starchy  compounds  are  more 
or  less  difficult  of  digestion,  and  during  the  progress  of  an  acute,  severe 
febrile  illness  they  must  be  employed  with  the  greatest  caution.  In  con- 
valescence and  in  chronic  invalidism,  however,  they  are  often  very  ser- 
viceable. In  making  these  preparations  it  is  essential  that  they  be  closely 
watched  and  stirred,  to  prevent  burning,  unless  they  be  cooked  over  hot 
water. 

To  make  oatmeal  porridge,  stir  two  ounces  (half  a  cupful)  of  crushed  oatmeal 
into  a  pint  of  milk,  previously  warmed,  and  afterwards  cook  from  twenty  to  thirty 
minutes  ;  add  salt  to  the  taste. 

To  make  baked  floiir  porridge,  a  very  excellent  porridge,  of  easy  digestion, 
and  especially  valuable  when  there  is  a  tendency  to  looseness  of  the  bowels,  take 
one  pint  of  flour,  pack  tightly  in  a  small  muslin  bag,  throw  it  into  boiling  water  and 
boil  for  five  or  six  hours,  cut  off  the  outer  sodden  portion,  grate  the  hard  core  fine. 
and  stir  into  boiling  milk  to  the  desired  thickness. 

To  make  arrow-root  porridge,  stir  two  teaspoonfuls  of  arrow-root  in  half  a 
teacupful  of  cold  milk  until  a  perfectly  smooth  mixture  is  made  ;  have  on  the  fire  a 
pint  of  milk,  and,  while  this  is  boiling,  add  the  arrow-root  little  by  little,  stirring 
constantly  until  cooked, — i.e.,  from  one  to  two  minutes  after  the  last  is  poured  in  ; 
add  sugar,  nutmeg,  and  wine,  according  to  taste  or  the  exigencies  of  the  case. 
When  milk  is  not  to  be  had,  or  a  very  low  diet  is  required,  water  may  be  substituted. 

The  secret  of  properly  preparing  arrow-root  is  in  having  the  first  mixture  with 
milk  absolutely  smooth  and  free  from  lumps. 

To  make  chocolate  porridge,  a  very  palatable  gruel  to  many  persons,  mix  to- 
gether one-quarter  pound  of  best  chocolate,  grated,  one-half  pound  of  rice  flour, 
two  ounces  of  arrow-root,  and  one-quarter  pound  of  loaf-sugar,  grated  ;  add  a  table- 
spoonful  of  this  mixture  to  a  pint  of  hot  milk,  and  let  it  boil  five  minutes ;  then 
remove  the  preparation  from  the  stove  and  serve  hot.  It  should  have  the  consist- 
ency of  gruel. 

To  make  tomato  porridge,  a  very  excellent  porridge  or  puree,  highly  nutritious 
and  useful  during  convalescence,  take  one  quart  of  canned  tomatoes,  bring  to  a 
boil,  strain  while  hot  through  a  hair  sieve  ;  bring  a  quart  of  milk  to  a  boil,  add  suf- 
ficient flour  to  make  a  thick  paste,  stir  in,  and  continue  to  boil  until  the  flour  is 
cooked  (about  twenty  minutes)  ;  stir  the  strained  tomatoes  gradually,  a  little  at  a 
time,  into  the  boiling  milk  ;  cook  five  or  ten  minutes,  seasoning  to  taste. 

To  make  sago  porridge  or  sago  jelly,  wash  the  sago  well  in  cold  water,  put  a 
small  teacupful  of  it  in  half  a  pint  of  water  to  soak  overnight,  and  in  the  morning 
put  this  mixture  into  one  pint  of  hot  water  ;  squeeze  into  it  the  juice  of  a  thinly 


FEEDING   OF  THE   SICK.  13 

pared  lemon,  and  allow  to  simmer  slowly  for  twenty  minutes  ;  then  sweeten,  add 
wine  according  to  taste  or  the  exigencies  of  the  case,  and  pour  into  moulds  to  cool. 
To  make  tapioca  porridge,  soak  two  tablespoonfuls  of  clean  tapioca  in  two 
teacupfuls  of  cold  water  overnight ;  in  the  morning  add  a  little  salt  and  one  pint  of 
milk,  or  water  if  milk  is  not  allowed  ;  simmer  until  quite  soft ;  stir  well  while 
cooling ;  when  done,  pour  into  a  bowl,  and  add  sugar,  wine,  and  nutmeg,  accord- 
ing to  taste  or  the  exigencies  of  the  case. 

ARTIFICIALLY  DIGESTED  FOODS. — In  low  fevers  the  powers  of  the 
alimentary  canal  are  certainly  much  impaired,  and  foods  which  have 
undergone  more  or  less  complete  artificial  digestion  outside  of  the  body 
are  very  useful. 

In  all  cases  in  which  the  typhoid  symptoms  are  severe,  milk  should 
constitute  the  chief  reliance,  and  should  be  partially  digested  before  ad- 
ministration. When  the  disease  is  prolonged,  and  especially  when  the 
mental  condition  is  clear,  the  patient  frequently  tires  of  milk.  Under  these 
circumstances  various  liquid  foods  prepared  by  the  partial  digestion  of 
solids  are  of  great  importance.  Artificially  digested  foods  are  also  of  value 
during  convalescence,  and  their  employment  constitutes  a  very  important 
part  of  the  treatment  of  gastric  and  intestinal  catarrhs.  Most  peptones 
have  a  distinctly  bitter  taste,  which  may  be  very  objectionable  in  indi- 
vidual cases.  This  taste  can  be  partially  overcome  by  the  addition  of 
flavoring  substances  or  extracts,  and  often  may  be  altogether  avoided  by 
arresting  the  process  of  artificial  digestion  before  completion. 

At  first  thought  pepsin  would  appear  to  be  the  most  available  ferment 
for  the  preparation  of  peptones  ;  but  practical  experience  has  led  to  re- 
liance upon  pancreatin.  Pancreatin,  pancreatic  extracts,  and  pancreatic 
liquors  are  now  found  abundantly  in  commerce.  The  superiority  of  the 
secretion  of  the  pancreatic  gland  as  a  practical  ferment  is  connected  with 
the  fact  that  it  contains  two  distinct  classes  of  digestive  principles, — 
namely,  pancreatic  diastase,  which  dissolves  starch,  and  trypsin,  which 
acts  upon  albuminous  principles.  It  is  of  great  importance  to  be  able  to 
determine  readily  the  value  of  any  preparation  of  pancreatin.  The  test 
devised  by  William  Roberts  {Digestive  Ferments,  London,  1881)  appears 
to  be  very  practical.  If  pancreatin  be  added  to  fresh  milk  without  an 
alkali,  in  the  course  of  a  few  minutes  the  liquid  acquires  the  property  of 
curdling  abundantly  upon  boiling  ;  and  Roberts  estimates  the  value  of  a 
pancreatin  by  the  number  of  cubic  centimetres  of  milk  which  are  trans- 
formed by  one  cubic  centimetre  of  the  sample  at  a  temperature  of  40°  C. 
to  the  curdling  point  in  five  minutes.  The  liquor  pancreaticus  used  by 
Roberts  had  a  power  oscillating  between  fifty  and  seventy.  A  test  which 
may  be  substituted  for  that  of  Roberts,  and  which  is  especially  applicable 
to  the  ordinary  pancreatic  extracts  or  so-called  pancreatin,  is  based  upon 
the  peptonizing  power  of  the  powder.  Five  grains  of  it  added  to 
twenty  grains  of  sodium  bicarbonate  should  so  alter  the  casein  contained 
in  one  pint  of  milk  at  a  temperature  of  115°  F.  in  an  hour,  that  no  coagu- 
lation will  occur  upon  the  addition  of  nitric  acid. 


14  FEEDING   OF   THE   SICK. 

To  make  peptonised  milk,  dilute  a  pint  of  milk  with  a  quarter  of  a  pint  of  water, 
heat  to  about  140°  F.,  add  two  teaspoonfuls  of  liquor  pancreaticus  (Roberts's)  with 
twenty  grains  of  sodium  bicarbonate,  digest  in  a  warm  place  for  an  hour  or  an  hour 
and  a  half,  raising  momentarily  to  the  boiling  point  ;  at  the  temperature  of  the 
sick-room,  65°  F.,  the  digestion  will  usually  require  about  three  hours.  Or  milk 
may  be  peptonized  by  dissolving  five  grains  of  pancreatin  with  twenty  grains  of 
sodium  bicarbonate  in  an  ounce  of  warm  water,  adding  to  a  pint  of  milk,  and  keep- 
ing at  a  temperature  of  1 10°  F.  for  one  hour.  Thoroughly  peptonized  milk  has  a 
disagreeable  bitter  taste,  so  that  in  practice  the  peptonizing  process  is  usually  not 
allowed  to  come  to  completion.  It  must,  however,  be  remembered  that  the  taste 
is  a  test  of  the  peptonizing,  and  that  the  so-called  peptonized  milk  which  has  no 
bitter  taste  is  simply  milk  mixed  with  pancreatin,  nothing  more.  Probably  the 
greater  part  of  the  peptonized  milk  given  to  the  sick  is  practically  simple  milk. 

To  m^fx.  peptonized  milk  gruel,  prepare  a  thick  gruel  with  arrow-root,  oatmeal, 
sago,  or  other  similar  farinaceous  articles,  add,  while  still  hot,  an  equal  quantity  of 
milk,  and  subsequently,  when  cooled  to  100°  F.,  for  each  pint  twenty  grains  of 
sodium  bicarbonate  and  two  teaspoonfuls  of  liquor  pancreaticus  or  five  grains  of 
pancreatic  extract,  digest  in  a  warm  place  for  two  hours,  boil  the  mixture  momen- 
tarily, and  strain. 

To  make  peptonized  beef  tea,  simmer  half  a  pound  of  minced  beef  for  two 
hours  in  a  pint  of  water  containing  twenty  grains  of  sodium  bicarbonate,  allow 
to  cool  to  about  100°  F.,  digest  at  this  temperature  with  a  tablespoonful  of  liquor 
pancreaticus  or  ten  grains  of  pancreatic  extract  for  three  hours,  decant  and  momen- 
tarily boil.  This  beef  tea  is  said  to  be  about  equivalent  to  milk  in  nutritive  value, 
containing  4.5  per  cent,  of  organic  solids,  three-fourths  of  which  is  peptone. 

To  make  peptonized  oysters,  a  palatable  and  nutritious  dish,  mince  six  large  or 
twelve  small  oysters,  and  add  to  them,  in  their  own  liquor,  five  grains  of  pancre- 
atic extract  with  twenty  grains  of  sodium  bicarbonate  ;  bring  the  mixture  to  100°  F., 
and  maintain,  with  occasional  stirring,  at  that  temperature  for  thirty  minutes,  then 
add  one  pint  of  milk  and  keep  the  temperature  steadily  up  for  ten  or  twenty  min- 
utes ;  finally  the  mass  is  to  be  brought  to  the  boiling  point,  strained,  and  served. 
Gelatin  may  be  added,  and  the  mixture  served  cold  as  a  jelly.  Cooked  tomato, 
onion,  celery,  or  other  flavoring  suited  to  the  individual  taste  and  condition  of 
the  patient  may  be  added  at  the  beginning  of  the  artificial  digestion. 

To  make  pancreatized  milk  toast,  digest  soft  milk  toast  for  from  thirty  to  fifty 
minutes  with  pancreatin  and  sodium  bicarbonate  until  it  becomes  an  almost  homo- 
geneous pulpy  mass,  which,  when  the  crusts  have  been  removed,  is  usually  readily 
retained  by  the  irritable  stomach.  In  extreme  cases,  however,  it  may  advanta- 
geously be  strained  and  the  fluid  portion  alone  used,  in  which  the  partially  pep- 
tonized solution  of  casein  of  the  milk  is  reinforced  by  the  actually  digested  gluten 
and  starch  of  the  bread,  together  with  a  very  little  dextrin.  Plain,  light  sponge- 
cake may  be  similarly  digested,  and  occasionally  forms  a  desirable  change. 

RECTAL  ALIMENTATION. — In  severe  gastritis  and  in  gastric  ulcer  it  is 
sometimes  necessary  to  enforce  a  temporary  or  even  a  somewhat  pro- 
longed abstinence  from  food.  In  diphtheritic  paralysis  of  the  throat,  as 
well  as  in  strictures  of  the  oesophagus,  it  may  be  almost  impossible  to  get 
food  into  the  stomach,  and  in  various  cases  the  food  is  vomited  whenever 
it  is  ingested.  Under  any  of  these  circumstances  feeding  by  the  rectum 
becomes  a  matter  of  the  utmost  importance.  There  is  no  reason  for  be- 
lieving that  the  rectal  or  even  the  colonic  secretions  have  digestive  power. 
Absorption  goes  on  slowly  from  the  rectum,  but,  according  to  Landois, 
very  rapidly  from  the  colon  itself.  For  these  reasons  injections  which  are 


FEEDING   OF  THE   SICK.  15 

used  for  the  purpose  of  nourishing  the  patient  should  be  bland,  concen- 
trated, and  thoroughly  digested  ;  peptonization  should  always  be  com- 
plete. Moreover,  the  material  should  be  thrown  high  up  into  the  colon. 
It  should  be  given  not  oftener  than  three  times  in  twenty-four  hours,  and 
the  colon  should  be  thoroughly  washed  out  by  a  high  injection  of  simple 
water  at  least  twice  in  the  twenty-four  hours.  If  there  be  irritability  of  the 
colon,  it  may  be  necessary  to  add  opium  to  the  nutritive  material  injected. 
Again,  in  many  cases  whiskey  or  brandy  may  be  very  useful.  In  most 
cases  it  is  best  to  give  the  injection  not  oftener  than  twice  in  the  twenty- 
four  hours,  and  to  wash  out  the  colon  an  hour  before  administration.  The 
presence  of  a  putrid  odor  in  the  discharges  is  evidence  that  more  food  is 
given  than  the  colon  can  work  up,  and  the  colon  is  as  much  irritated  by 
overfeeding  as  is  the  stomach.  In  colonic  as  well  as  in  gastric  feeding  it 
is  the  amount  absorbed  and  not  the  amount  ingested  that  does  good. 

In  1872,  from  the  pancreas  of  swine  or  cattle,  W.  O.  Leube  made  a 
food  preparation  which  he  experimentally  proved  to  yield  nutritive  material 
to  the  blood  of  dogs  when  injected  into  the  colon,  and  by  whose  colonic 
exhibition  he  maintained  life  for  four  weeks  in  a  patient  whose  stomach 
rejected  all  food.  Leube' s  formula  may  be  found  in  detail  in  the  tenth 
edition  of  this  book,  but  is  here  omitted  because  it  has  no  superiority 
over  preparations  made  with  commercial  pancreatic  extracts.  As  milk 
and  eggs  contain  all  the  food  necessary  for  the  sustenance  of  life,  and  are 
more  rapidly  and  readily  digested  than  is  meat,  all  that  is  necessary  is  to 
digest  them  thoroughly  before  injection.  From  half  a  pint  to  a  pint  of 
milk  with  two  or  three  eggs  may  be  employed  at  each  injection.  It  is 
however  impossible  to  maintain  nutrition  with  rectal  feeding  for  any 
length  of  time. 


CHAPTER    II. 

THE   TREATMENT    OF    SYSTEMIC    STATES. 

EXHAUSTION   AND    NEURASTHENIC   CONDITIONS. 

DEPRESSION  is  a  condition  of  temporarily  lowered  vital  activity  pro- 
duced by  the  presence  of  some  poison  in  the  system.  Exhaustion  is  a 
condition  of  absolute  lack  of  power  in  which  the  functional  activity  is 
repressed,  not  by  a  depressing  substance,  but  by  the  inability  of  the  affected 
part.  In  practice  it  is  essential  to  distinguish  between  these  two  states. 
The  one  requires  treatment  by  stimulants,  while  the  other  is  often,  al- 
though temporarily  relieved,  permanently  aggravated  by  the  use  of  stimu- 
lants. Exhaustion,  especially  of  the  nervous  system,  is  frequently  spoken 
of  as  a  disease,  under  the  name  of  neurasthenia.  It  is  not  a  disease,  how- 
ever, but  a  condition,  which  may  be  the  result  of  overstrain  or  overwork 
or  of  some  chronic  disease.  It  is  essential  that  in  every  case  of  alleged 
neurasthenia  very  careful  examination  should  be  made  to  detect  the  pres- 
ence of  organic  kidney  disease,  chronic  diarrhoea,  or  other  possible  cause 
of  the  exhaustion.  The  amount  of  work  necessary  to  produce  neuras- 
thenic exhaustion  is  dependent  upon  the  original  amount  of  power  in  the 
organism.  In  persons  born  of  neurotic  feeble  parentage  or  of  parents 
exhausted  by  overstrain,  the  working  power  may  be  very  slight.  Ex- 
haustion may  be  local  or  it  may  be  general.  This  applies  to  the  nervous 
system  as  well  as  to  the  other  apparatus  of  the  body.  A  local  nervous 
exhaustion  tends  towards  developing  into  a  general  condition.  Thus,  a 
writer's  palsy  may  be  the  first  symptom  of  a  general  break-down.  Sper- 
matorrhoea, at  first  due  purely  to  local  exhaustion  of  the  implicated  nerve- 
centres,  if  unchecked  very  generally  develops  into  general  neurasthenia. 
The  same  is  true  of  cerebral  exhaustion  following  excessive  mental  work. 
The  exhaustion  is  to  be  relieved  only  by  recuperation,  and  recuperation 
is  to  be  obtained  only  by  rest  and  the  assimilation  of  food.  The  nature 
of  the  rest  depends  upon  the  character  of  the  exhaustion.  In  cases  of 
pure  cerebral  exhaustion  with  the  bodily  powers  untouched  and  the 
physical  powers  not  much  implicated,  freedom  from  care  and  from  all 
mental  work,  conjoined  with  life  in  the  open  air,  is  the  essential  of  cure. 
It  must  be  remembered  that  sight-seeing  is  as  exhausting  to  the  brain  as 
is  the  hardest  study,  and  that  in  extreme  cases  even  the  seeing  of  friends 
may  overtax  the  brain,  so  that  isolation  may  be  essential.  Such  isolation 
may  be  obtained,  if  the  bodily  powers  remain  good,  by  travel  in  the  wil- 
16 


EXHAUSTION   AND   NEURASTHENIC   CONDITIONS.     17 

derness,  or  on  the  ocean,  or  in  other  positions  where  intercourse  with  the 
world  is  impossible.  In  cases  of  extreme  neurasthenia  or  nervous  exhaus- 
tion the  so-called  rest-cure  is  a  method  of  treatment  of  great  value.  It  is 
essential  for  its  successful  employment  that  it  be  modified  to  suit  the 
needs  of  the  individual  case  :  if  employed  as  a  set  mould  into  which  every 
case  is  to  be  forced,  it  will  frequently  do  harm. 

The  principles  of  the  rest-cure  are  absolute  rest,  forced  feeding,  and 
passive  exercise.  Absolute  rest  is  often  prescribed  by  the  physician  with- 
out being  sufficiently  definite  and  insisted  upon.  When  it  is  desired  to 
apply  it  most  strictly,  it  should  be  clearly  explained  that  the  patient  is 
not  to  be  allowed  to  get  out  of  bed  even  to  pass  urine  or  faeces,  nor  to 
feed  himself  or  herself,  nor  perform  any  act  of  the  toilet  whatsoever.  The 
rest  also  must  be  for  the  mind  as  well  as  for  the  body,  and  it  is  essential 
that  the  patient  be  isolated.  In  obstinate,  severe  cases  of  neurasthenia 
complete  and  absolute  isolation  is  a  sine  quti  non,  and  especially  when 
there  is  a  decidedly  hysterical  element  is  it  necessary  to  separate  the 
patient  entirely  from  her  friends.  Under  these  circumstances  there  must 
be  a  well-trained  nurse  who  is  personally  agreeable  to  the  patient.  The 
confinement  would  be  very  irksome  to  any  except  the  most  exhausted 
patient  were  it  not  for  the  daily  visit  of  those  engaged  in  the  treatment. 
To  provide  further  against  ennui,  the  nurse  should  be  a  good  reader,  so 
that  under  the  definite  instructions  of  the  physician  she  can  occupy  a 
certain  portion  of  the  time  in  reading  to  the  patient. 

In  order  to  maintain  the  functions  of  the  skin,  the  patient  should  be 
well  sponged  with  hot  water  in  bed  every  morning  after  breakfast.  A 
strong  solution  of  salt,  or,  better,  sea-brine,  is  to  be  preferred  to  simple 
water,  and  frequently  it  may  be  followed  by  the  use  of  alcohol.  In  very 
feeble  cases  the  alcohol  may  be  employed  alone.  We  have  seen  very 
good  effects  from  momentarily  rubbing  each  portion  of  the  skin  with 
ice  just  after  bathing.  When  rubbing  with  ice  is  practised,  the  water 
used  in  the  bathing  should  be  as  hot  as  can  be  borne.  In  giving  the  bath 
the  patient  should  be  stripped,  and  lie  between  blankets,  so  that  exposure 
of  the  whole  body  is  avoided  while  each  part  is  thoroughly  washed.  No 
exertion  on  the  part  of  the  patient  should  be  allowed.  Women  should 
not  be  permitted  to  arrange  their  own  hair. 

The  question  of  feeding  is  one  of  great  importance,  and  requires  the 
utmost  care  and  attention  from  the  physician.  The  end  to  be  attained  is 
to  feed  the  patient  as  much  as  can  be  digested,  but  not  to  overfeed  and 
derange  the  digestion.  Food  should  be  given  at  intervals  of  two  or  three 
hours,  and  must  be  both  light  and  nutritious.  It  should,  at  least  at  first, 
consist  largely  of  milk,  except  in  those  rare  cases  in  which  that  fluid  does 
really  disagree  with  the  stomach  and  is  not  merely  thought  to  do  so.  The 
milk  should  be  skimmed  or  given  in  the  form  of  koumiss.  Beef  juice  and 
other  concentrated  meat  essences  are  valuable  as  stimulants,  and  may  be 
used  especially  as  the  basis  of  soups.  Various  farinaceous  articles  of  food 
may  be  added  to  them  :  if  an  egg  be  stirred  into  the  concentrated  bouillon 


i8  THE   TREATMENT   OF   SYSTEMIC   STATES. 

or  beef  essence  just  as  it  ceases  boiling,  a  nutritious  and  to  many  persons 
palatable  dish  is  obtained.  When  constipation  exists,  oatmeal  porridge, 
Graham  bread,  and  fresh  or  dried  fruits  may  be  allowed  if  readily  digested 
by  the  patient.  In  order  to  give  an  idea  of  a  general  plan  of  the  dietary, 
the  following  schedule  of  the  daily  life  is  given.  It  must  be  altered  from 
day  to  day,  so  as  not  to  weary  the  patient  by  its  monotony.  Such  a 
schedule  should  always  be  put  in  the  hands  of  the  nurse,  who  should  be 
required  to  follow  it  strictly.  Success  will  in  a  great  measure  depend 
upon  the  practical  skill  and  tact  of  the  physician  in  his  adaptation  of  the 
diet  to  the  individual  requirements  of  the  case  : 

8  A.M.  Rolls  or  toast ;  cocoa  or  weak  coffee,  or  roasted  wheat  coffee ;  beef- 
steak, tenderloin,  or  mutton-chop. 

9  A.M.  Bathing. 

11  A.M.  Oatmeal  porridge,  with  milk,  or  else  a  pint  of  koumiss. 

12  M.  Massage. 

2  P.M.  Dinner :  bouillon  with  or  without  egg  ;  beefsteak,  rice,  roast  white 
potatoes ;  dessert  of  bread-pudding,  blanc-mange,  or  similar  farinaceous  articles 
of  diet. 

4  P.M.  Electricity. 

5  P.M.  Milk  toast. 

9  P.M.  Half  a  pint  of  skimmed  milk  or  koumiss. 

In  many  cases  the  patient  at  first  can  take  very  little  food,  and  it  is 
frequently  best  to  begin  the  treatment  with  an  entirely  liquid  diet,  giving 
milk  every  two  hours,  or  some  nutritious  soup,  with  milk  or  plain  farina- 
ceous food,  and  only  after  a  time  gradually  accustoming  the  patient  to 
solid  food.  Not  rarely  a  prolonged  treatment  by  the  so-called  milk  diet 
is  of  avail.  The  rest-cure  is,  indeed,  largely  based  upon  a  careful  regu- 
lation of  the  food. 

Passive  exercise  is  to  be  obtained  by  the  use  of  electricity  and  massage, 
the  object  being  to  get  the  effects  of  exercise  upon  the  nutrition  and  cir- 
culation without  the  expenditure  of  the  patient's  nerve-force.  By  the  use 
of  electricity  muscular  contractions  are  secured  that  simulate  those  which 
are  voluntary,  and  more  or  less  thoroughly  replace  them. 

The  faradic  current  is  alone  used.  It  is  applied  in  two  ways  :  first,  to 
the  individual  muscles  ;  second,  to  the  whole  body.  The  s6ances  should 
be  daily,  the  operator  beginning  at  the  hand  or  the  foot,  and  systematically 
faradizing  each  muscle  of  the  extremities  and  the  trunk. 

The  slowly  interrupted  current  is  generally  preferable,  but  advantage 
is  sometimes  gained  by  varying  the  rapidity  of  the  interruptions.  The 
general  rule  is  to  select  that  current  which  produces  most  muscular  con- 
traction with  the  least  pain.  The  poles  should  be  applied  successively 
to  the  motor  points  of  the  muscles,  so  as  to  contract  each  firmly  and 
thoroughly.  This  process  should  occupy  from  thirty  to  forty  minutes. 
The  electrodes  are  then  to  be  replaced  by  large  sponges  well  dampened 
with  salt  water  :  one  of  these  should  be  put  at  the  nape  of  the  neck  and 
the  others  against  the  soles  of  the  feet,  and  a  rapidly  interrupted  current, 


EXHAUSTION  AND   NEURASTHENIC   CONDITIONS.      19 

as  strong  as  the  patient  can  bear,  should  be  sent  through  the  body  for 
twenty  minutes  or  half  an  hour.  It  is  unnecessary  for  the  physician  to 
remain  during  this  time.  In  some  cases  the  electrical  programme  may  be 
varied  so  as  to  get  a  local  stimulant  action  from  the  general  current. 
Thus,  when  digestion  is  enfeebled  and  the  bowels  are  costive,  for  a  portion 
of  the  time  one  of  the  sponges  may  be  placed  upon  the  epigastric  region. 
In  women,  when  there  is  great  abdominal  and  pelvic  relaxation,  one  pole 
may  be  placed  high  up  in  the  vagina.  We  have  seen  old-standing  pro- 
lapsus cured  in  this  way. 

The  principle  of  rest-cure  for  the  relief  of  exhaustion  has  a  very  wide 
application.  Thus,  in  the  treatment  of  acute  diseases,  such  as  typhoid 
fever,  in  which  death  results  from  exhaustion,  it  is  of  the  utmost  impor- 
tance that  absolute  rest  be  prescribed  very  early.  Before  the  diagnosis 
can  be  certainly  established,  and  when  there  is  merely  a  suspicion  of 
typhoid  fever  developing,  the  patient  should  be  put  to  bed,  and  should 
not  be  allowed  to  get  out  for  any  purpose.  One  great  object  of  nursing 
is  the  saving  of  the  strength  of  the  patient  and  the  prevention  of  exhaus- 
tion by  disturbance.  Mere  uncleanliness,  a  low  voice  to  a  deaf  patient,  a 
loud,  high-pitched  voice  to  one  whose  hearing  is  acute,  failure  to  under- 
stand quickly  the  whims  and  caprices  of  a  sick  man  or  woman,  are  tor- 
menting things,  which  may  take  away  the  rest  and  even  destroy  the  life 
of  a  patient.  It  is  almost  equally  essential  that  all  fussiness  be  avoided. 
The  nurse  who  is  continually  asking  the  patient  whether  he  will  have  this 
or  that,  or  wants  this  or  that,  or  is  shifting  the  blinds,  or  fixing  the  fur- 
niture, or  moving  about  unnecessarily,  may  not  only  be  disagreeable,  but 
may  do  great  harm. 

In  applying  the  rest-cure  to  the  treatment  of  the  individual  case,  it 
must  be  remembered  that  the  system  is  based  upon  certain  principles,  and 
that  these  principles  are  frequently,  in  the  individual  case,  best  carried 
out  by  a  modification  of  the  details  of  the  plan  which  has  been  given.  Not 
rarely  advantage  is  obtained  by  daily  sending  the  patient  out  carriage- 
riding,  or  even  from  taking  walking  exercise  once  a  day.  In  other 
cases  the  rest-cure  may  be  very  advantageously  combined  with  more 
protracted  out-door  life  and  exercise,  the  patient  being  required  simply 
to  pass  twelve,  fourteen,  or  sixteen  hours  out  of  the  twenty-four  in  bed 
and  the  remaining  time  in  the  open  air.  It  is  impossible,  within  moderate 
scope,  to  describe  all  the  modifications  of  the  method  which  will  occur  to 
the  skilful  physician. 

The  time  of  continuance  of  the  rest-cure  varies  greatly  :  even  in 
extreme  cases  the  patient  should  be  allowed  to  sit  up  at  the  end  of  six  or 
at  most  eight  weeks,  and  in  many  instances  three  weeks  of  seclusion  is  all 
that  is  absolutely  essential.  The  period  of  convalescence  requires  care. 
An  attempt  to  return  rapidly  to  the  performance  of  household  duties  or 
to  the  ordinary  labors  of  life  will  usually  dissipate  the  acquired  strength, 
and  for  the  gain  to  be  permanent  it  is  in  most  cases  necessary  that  the 
patient  be  sent  to  some  quiet  sea-shore,  mountain,  or  country  resort,  in 


20  THE  TREATMENT   OF   SYSTEMIC   STATES. 

order  by  out-door  life  and  gradually  increasing  exercise  to  harden  into 
permanent  form  the  flesh  and  strength  which  have  been  laboriously 
gathered. 

TREATMENT    OF    CORPULENCE. 

In  the  treatment  of  corpulence  it  must  be  remembered  in  the  first 
place  that  the  same  line  of  treatment  is  not  suitable  for  every  case. 
Speaking  broadly,  we  may  divide  cases  of  corpulence  into  two  classes 
(excepting  those  associated  with  some  apparent  organic  cause)  :  those 
due  to  defective  oxidation  and  those  due  to  excessive  food-supply.  The 
patients  of  the  first  class  are  mostly  anaemic  and  of  little  muscular  power, 
while  those  of  the  second  are  plethoric  and  robust,  and  their  excretion  of 
urea  is,  as  a  rule,  much  above  normal. 

For  the  purposes  of  prognosis  this  division  of  obesity  is  very  impor- 
tant. In  the  overfed,  reducing  the  food-supply  may  be  all  that  is  needed  ; 
in  the  so-called  "  fat  anaemics"  it  may  be  very  difficult  or  perchance  im- 
possible to  increase  oxidation  ;  hence  in  those  who  are  at  once  fat  and 
feeble  the  prognosis  is  grave  in  proportion  to  the  feebleness.  For  the 
purposes  of  therapeusis  the  division  is  not  so  important  as  it  may  seem  at 
first  sight,  excepting  in  so  far  that  it  points  out  that  in  a  fat  anaemic  the 
effect  of  regulating  the  diet  is  less  than  it  is  in  those  who  are  obese  and 
plethoric.  In  each  class  it  is  essential  to  increase  oxidation  as  much  as 
possible,  since  few  persons  will  tolerate  prolonged  semi-starvation.  The 
fat  anaemic  often,  however,  bear  rigid  dieting  badly,  and  with  them,  there- 
fore, great  care  must  be  exercised  in  the  reduction  of  the  food. 

Certain  drugs  have  some  influence  in  increasing  oxidation  ;  in  the 
anaemic,  iron  seems  to  increase  the  activity  of  the  destructive  processes 
of  the  body  and  to  aid  in  reducing  flesh.  On  the  other  hand,  in  such 
subjects  the  alkalies,  especially  the  potash  salts,  though  they  increase 
tissue-waste,  may  be  harmful  and  augment  the  weakness.  Contrariwise, 
however,  when  there  is  an  abundance  of  strength  in  an  obese  subject,  the 
continuous  use  of  alkalies,  and  especially  of  alkaline  laxatives,  may  be  of 
great  service.  It  must  be  remembered  that  very  often  in  these  cases 
there  is  lack  of  activity  in  the  intestinal  glands  and  much  retention  of 
half-assimilated  materials. 

The  value  of  Kissingen,  Carlsbad,  and  other  alkaline  purgative  waters, 
and  the  results  sometimes  obtained  in  obesity  by  treatment  at  the  various 
alkaline  spas,  are  very  familiar  ;  but  the  alkaline  laxative  ought  to  be, 
as  it  is  in  fact  at  the  various  springs,  used  only  as  an  adjuvant  to  the 
more  serious  treatment.  The  keeping  of  the  patient  in  a  state  of  chronic 
purgation  is,  after  all,  but  a  crude  method  of  affecting  metabolism,  and 
if  too  prolonged  may  have  a  local  injurious  effect  on  the  intestinal  tract. 

The  use  of  the  thyroid  gland  in  obesity  will  be  considered  at  greater 
length  in  another  portion  of  this  book.  It  is  enough  here  to  point  out 
that  the  extract  of  the  gland  does  increase  oxidation  of  the  carbohydrates 
of  the  body,  and  that  therefore  it  is  often  useful  in  the  treatment  of 


TREATMENT   OF   CORPULENCE.  21 

obesity  as  an  addition  to  the  regulation  of  the  food  and  the  use  of  exercise. 
Given  in  excess  it  produces  deleterious  results,  and  when  used  for  too  long 
a  time  appears  to  largely  lose  its  power. 

The  natural  and  most  important  means  at  command  for  the  increasing 
of  oxidation  is  exercise,  and  the  practice  of  regulated  exercise  is  at  the 
basis  of  all  proper  systems  of  weight-reduction. 

The  amount  and  form  of  exercise  to  be  prescribed  in  any  individual 
case  depend  upon  the  peculiarities  of  the  patient  and  his  surroundings. 
Certain  general  principles,  however,  apply  to  every  case,  and  if  these  are 
observed  the  details  may  vary  indefinitely.  First,  the  exercise  must  be 
regular  and  persistent  ;  second,  it  must  involve  not  only  certain  muscles, 
but  all  the  muscles  of  the  body  ;  third,  it  must  be  sufficient  in  amount  to 
produce  an  effect, — it  should  always,  indeed,  be  carried  as  far  as  is  pos- 
sible without  the  production  of  exhaustion  ;  fourth,  it  must  be  sufficiently 
active  to  produce  sweating,  which,  in  many  cases,  may  be  encouraged  by 
the  use  of  warm  clothing  during  exercise.  Professional  trainers,  indeed, 
attach  much  importance  to  sweating  as  a  means  of  reducing  weight.  It 
probably  acts  not  only  by  dehydrating  the  body,  but  also  by  hastening 
the  elimination  of  partially  used-up  materials,  and  is  particularly  indicated 
when  there  is  any  gouty  tendency.  In  selecting  the  form  of  exercise  care 
should  be  taken  that  it  be  as  little  irksome  as  possible  to  the  patient,  and 
if  it  can  be  made  a  pleasure  much  will  be  gained. 

Bicycling  offers  an  inexpensive  and  convenient  means  of  muscular 
exertion,  but  has  the  disadvantage  of  not  calling  into  play  the  muscles  of 
the  shoulders  and  arms.  Golf  seems  to  have  an  attraction  for  its  devotees 
strong  enough  to  make  them  forget  that  they  are  under  "the  doctor's 
orders."  A  travelling  or  hunting  trip  through  the  wilderness  of  the 
Rocky  Mountains  or  the  forests  of  Maine  or  Canada  affords,  as  we  can 
vouch  for  from  personal  experience,  a  most  efficient,  and  to  those  who 
are  willing  to  forego  some  of  the  luxuries  of  civilization  a  pleasant,  method 
of  reducing  flesh. 

A  foot-exercise  with  whose  fat-destroying  tendency  every  trainer  is 
familiar  is  running.  The  influence  which  it  has  upon  heart  and  lungs 
does  not  differ  from  that  of  mountain-climbing,  and,  if  there  be  any  truth 
in  the  teachings  of  Oertel  as  to  the  value  of  pulmonic  and  cardiac  gym- 
nastics, running  ought  to  be  of  especial  value  when  the  heart  and  lungs 
are  giving  evidences  of  being  specially  affected  by  the  fat-accumulation. 
Boat-rowing,  or  even  canoeing,  may  serve  the  purpose  of  the  fat  man. 
Wood-sawing  is  largely  employed  in  some  European  anti-fat  sanitariums, 
and  is  undoubtedly  efficient.  It  can  be  very  readily  graduated  by  re- 
quiring one  or  two  sticks  more  to  be  sawn  each  successive  day.  Gym- 
nastic exercise,  lifting  of  weights  with  pulleys,  etc. ,  may  be  employed, 
and  even  horseback-riding  may  be  made  efficient.  Oertel  further  be- 
lieves that  mountain-climbing  affords  a  method  of  gymnastically  training 
the  heart  and  lungs  which  may  be  of  the  greatest  service  in  the  treatment 
of  a  weak  heart. 


22  THE  TREATMENT   OF   SYSTEMIC   STATES. 

It  must,  however,  be  remembered  that  the  heart  is  in  an  essentially  different 
position  from  the  voluntary  muscle.  The  muscle  loses  its  power  through  want  of 
exercise,  and  is  brought  back  from  its  soft,  flaccid  condition  by  exercise.  Weak- 
ness of  the  heart-muscle,  on  the  other  hand,  is  practically  never  the  result  of  lack 
of  exercise  of  the  heart,  but  is  due  to  the  accumulation  of  fat  about  the  muscular 
fibres  or  to  degeneration  of  the  muscle,  to  exhaustion  from  overwork,  or  to  the 
presence  of  some  poison  in  the  blood.  If  the  cardiac  weakness  be  connected  with 
a  fatty  change  in  the  muscle  which  is  the  result  of  general  fatty  infiltration  of  the 
body,  the  removal  of  such  fat-infiltration  will  be  accompanied  by  improvement  of 
the  muscle  of  the  heart,  which  improvement  may  probably  be  aided  by  cardiac  ex- 
ertion. If,  on  the  other  hand,  the  cardiac  weakness  is  the  result  of  overstrain  or 
of  a  true  fatty  degeneration,  the  probabilities  are  that  it  will  be  increased  rather 
than  diminished  by  cardiac  exertion. 

In  all  cases  the  exercise  should  at  first  be  gentle  and  should  be  in- 
creased very  carefully.  Thus,  mountain-climbers  or  runners  should  at  first 
stop  every  few  feet,  to  allow  heart  and  lungs  to  recover  themselves.  Due 
regard  must  be  had  for  the  patient's  general  condition  ;  especially  must  it 
be  remembered  that  the  stout,  flabby  body  is  often  associated  with  a  weak 
heart-muscle  which  sudden  severe  exertion  may  easily  overtax.  Dis- 
regard of  this  fact  has  indeed  occasionally  led  to  a  fatal  result. 

The  fat  of  the  body  is  chiefly  if  not  exclusively  derived  from  the 
hydrocarbons  of  the  food.  The  notorious  diet-list  of  Mr.  Banting,  which 
gave  rise  to  the  term  "  bantingism,"  was  in  no  respect  novel,  but  only 
conformed  to  the  universally  recognized  principle  that  in  corpulency  with- 
drawal of  carbohydrates  from  the  food  is  necessary. 

The  extent  to  which  the  diet  can  be  reduced  depends,  at  least  in  the 
plethoric  group  of  cases,  almost  entirely  on  the  patient's  strength  of  will. 
To  accomplish  any  good  the  intake  must  self-evidently  be  less  than  the 
output, — that  is,  the  demands  of  the  system  must  never  be  satisfied,  and 
the  body  must  obtain  the  necessary  force  from  the  energy  stored  up  in 
the  fatty  tissues.  In  short,  the  patient  must  undergo  a  mild  form  of  star- 
vation. The  craving  for  food  can  be  to  some  extent  assuaged  by  the  fat- 
free  proteids  ;  but  as  these  are  insufficient  for  the  needs  of  a  healthy 
organism,  no  amount  of  them  will  entirely  satisfy  the  appetite. 

It  is,  therefore,  plainly  impossible  to  overcome  the  repugnance  of 
patients  to  the  diet  by  indefinitely  increasing  meat  and  other  nitro- 
genous foods.  Further,  the  excessive  use  of  nitrogenous  foods  throws  a 
strain  upon  the  kidneys  in  requiring  them  to  cast  off  an  excessive  amount 
of  waste  material  ;  and  if  in  such  cases  there  be  a  gouty  diathesis  there 
is  danger  of  the  production  of  arthritic  symptoms. 

No  single  dietary  is  suitable  for  all  cases  ;  the  practitioner  should  make 
a  list  in  accordance  with  the  circumstances  of  the  individual  case.  In 
such  list  the  actual  weight  of  food  to  be  taken  should  be  given,  as, 
without  such  check,  the  hungry  man  will  always  eat  more  than  he  be- 
lieves he  does.  As  samples  we  give,  however,  two  dietary  lists — the  first 
is  that  of  Banting  ;  the  second,  which  was  devised  by  Ebstein,  has  been 
much  used  in  Germany,  and  seems  to  us  the  better  of  the  two. 


TREATMENT   OF   CORPULENCE.  23 

BANTING. 

6  A.M.  One  pint  of  black  coffee  and  one  ounce  of  coarse  brown  bread  or  biscuit. 

9  A.M.  Four  ounces  of  lean  meat,  three  ounces  of  brown  bread  or  biscuit,  and 
half  a  pint  of  coffee. 

2  P.M.  Six  ounces  of  lean  meat,  three  ounces  of  brown  bread  or  biscuit,  six 
ounces  of  green  vegetables,  and  half  a  pint  of  water,  followed  by  half  a  pint  of 
coffee. 

6  P.M.  Half  a  pint  of  coffee. 

At  supper  two  ounces  of  brown  bread  or  biscuit,  and  a  couple  of  glasses  of 
sherry  or  claret.  Fruit  ad  libitum,  liquorice  powder  pro  re  nata. 

EBSTEIN. 

BREAKFAST.— Two  hundred  and  fifty  grammes  of  tea  without  sugar  or  milk  ; 
fifty  grammes  of  white  bread,  with  plenty  of  butter. 

LUNCH. — Fatty  soup,  made  from  a  marrow-bone  ;  from  one  hundred  and  twenty 
to  one  hundred  and  eighty  grammes  of  flesh,  containing  much  fat ;  some  vegetables  ; 
stewed  fruit  without  sugar  ;  two  or  three  glasses  of  wine.  Later  in  the  afternoon, 
one  cup  of  tea  without  milk  or  sugar. 

EVENING. — One  cup  of  tea  without  milk  or  sugar,  thirty  grammes  each  of  bread 
and  butter,  one  egg,  or  a  piece  of  fat  ham  or  fat  roast  meat,  or  cheese,  and  fresh 
fruit ;  no  alcohol. 

The  following  table,  based  upon  the  analysis  of  Carl  Zahn,  shows  the 
comparative  amounts  of  the  different  forms  of  food  furnished  by  the  rations 
of  Banting  and  of  Ebstein  contrasted  with  the  average  normal  : 

Albuminous  Materials.  Fat.  Carbohydrates. 

Normal  ....  30.  drachms.  25.  drachms.  92.  drachms. 
Banting  ....  25.5  drachms.  2.  drachms.  5.25  drachms. 
Ebstein  ....  25.5  drachms.  21.25  drachms.  11.75  drachms. 

As  a  foundation  upon  which  the  physician  may  arrange  his  bill  of 
fare,  the  following  table,  originally  compiled  by  Zahn,  is  appended.  It 
gives  the  approximate  amount  of  food-material  in  various  common  articles 
of  diet  in  parts  by  weight. 


Food. 

Water. 

Albu- 
min. 

Fat. 

Hydro- 
carbons. 

Mean  of  ten  different  kinds  of  simple  soups   .   . 
Mean  of  ten  rich  soups         

91- 

8l  2 

I.I 
2  6 

r-5 

7.  2 

5-7 
Q  7 

Boiled  beef,  lean,  from  young  heifer    

66.=. 

28  4. 

1.7, 

Boiled  beef,  fat,  from  young  heifer   

AQ 

18 

12.  1 

Beef  from  steers  and  oxen,  boiled     

«;68 

7A  2 

7.5 

O  4, 

Beef  from  steers  and  oxen,  roasted  
Roast  meats,  including  beefsteak,  game,  birds, 
etc.,  reckoned  as  an  average      

59- 
s8 

38.2 

l8  2 

1-7 
2.7 

Veal,  roasted                         

78 

1C    7 

52 

Fricasseed  veal   with  fat  and  milk    

£7 

22  3. 

IO  4. 

IO. 

Fat  roasted  pork  or  goose  

4O 

Z 

•tA   6 

24.  2 

Smoked  ham  

CQ  77 

25  08 

8  II 

Boiled  fish    

74  2O 

22  IO 

o  60 

o.7o 

Shell-fish  

80  Q7 

17  OQ 

O   TA. 

Mean  of  seven  different  kinds  of  meat-foods  .   . 

44.20 

8.70 

15. 

28.9 

THE   TREATMENT   OF   SYSTEMIC   STATES. 


Food. 

Water. 

Albu- 
min. 

Fat. 

Hydro  - 
carbons. 

72  4O 

I   QO 

i  3.0 

21  2O 

7-1 

2   IO 

320 

21  80 

Potatoes   boiled             .    .           

7O 

I  80 

3IO 

24 

Salad  green                       ...       

Q/i     2 

I   4O 

2 

2  2 

Vegetables  in  general  average  • 

62  2 

6  40 

I  4O 

White  bread     ...           

AO  4S 

6  is 

O  /I  /I 

SI   12 

Black  bread         

•5J 

ii 

S7 

i  18 

T  1   "it 

5    !8 

81  08 

Milk       

8?  42 

3A1 

-5  6s 

4  81 

Cream       .       

6s  si 

T.  61 

26  7  S 

•i  C2 

QO  27 

4  06 

O  Q7. 

•3  77 

Butter    

I  A   AQ 

O  71 

8-t  27 

o  s8 

•ic  CQ 

17  AA 

40  80 

S  21 

Lard  

O  7O 

o  26 

OO  O/l 

Sugar    ,                                           ... 

2  l6 

O  3S 

06  12 

Vinegar     ....           .    .              

QA 

O  4 

One  egg,  estimated  not  by  percentage,  but  by 
amount  in  average  egg     

8  2S  3 

I   A  "T 

I    7C  T 

O  OS  "Z 

Tea    ....              

Q7  Q 

O  1 

o  6 

Coffee    

Q4  7 

o  18 

O  S2 

I  4 

Q-3    7. 

i  60 

2  2O 

i  6 

80 

•3  7 

9  6 

T.  8 

It  is  the  general  custom  to  reduce  the  amount  of  water  in  the  treat- 
ment of  corpulent  persons.  This  practice  is  apparently  opposed  to  all 
our  present  knowledge  of  physiology  ;  it  is  impossible  to  see  how  water 
can  increase  the  formation  of  fat,  and  theoretically  it  would  seem  that  it 
should  hasten  the  catabolic  processes  of  the  body.  It  may  be.  however, 
that  empiricism  has  passed  science,  and  that  the  common  belief  is  correct, 
although  we  confess  that  we  follow  its  beckoning  with  reluctance.  Es- 
pecially in  those  cases  where  there  is  a  lithsemic  tendency,  as  there  usually 
is  in  the  plethoric  type  of  corpulence,  the  stoppage  of  water  may  do  much 
harm  by  encouraging  the  retention  of  gouty  poisons  in  the  system. 

LITHIASIS. 

Although  the  gouty  diathesis  is  one  of  the  most  frequent  of  bodily 
complaints  in  middle-aged  persons  of  the  upper  class,  and  an  enormous 
amount  of  study  and  research  has  been  devoted  to  the  determination  of 
its  dietetic  treatment,  yet  no  positive  scientific  knowlege  exists  for  our 
theoretic  guidance.  This  is  the  fault  of  the  pathologist  rather  than  of  the 
therapeutist.  The  ultimate  nature  of  the  gouty  diathesis  remains  as  much 
unknown  as  the  ultimate  nature  of  syphilis.  We  are  therefore  forced  to 
rely  upon  an  unsatisfactory  empiricism. 

It  would  be  very  easy  to  quote  contradictory  statements  from  various 
clinicians  of  authority.  In  the  brief  space  here  possible  it  seems  wisest  to 
avoid  both  theoretic  discussion  and  quotations  from  authorities,  and  we 
shall  give  simply  our  own  views  as  based  upon  wide  reading  and  very 
large  experience  in  the  treatment  of  gouty  patients. 

In  the  hygienic  treatment  of  gouty  patients  it  is  essential  that  exercise 


LITHIASIS.  25 

be  taken  systematically  and  with  regularity.  If  circumstances  permit, 
prolonged  moderate  exercise  in  the  open  air  (such  as  may  be  obtained  by 
horseback-riding,  rowing,  hunting,  etc. ,  or  even  by  walking)  is  to  be  pre- 
ferred. Gymnastic  or  house  exercises  may  very  well  be  substituted  for 
this  out-door  work  under  special  circumstances.  The  form  is  not  a  matter 
of  much  importance,  provided  the  exercise  involves  the  whole  muscular 
system.  The  amount  of  exercise  must  be  graduated  to  the  needs  of  the 
individual  case,  different  persons  having  no  more  the  same  measure  of 
physical  strength  or  the  same  needs  for  physical  work  than  have  different 
measures  the  same  capacity.  The  endeavor  must  be  always  to  push  the 
exercise  until  it  produces  distinct  physical  weariness,  and  a  better  effect 
will  usually  be  obtained  if  the  exertion  be  sufficiently  violent  to  cause  free 
sweating.  For  the  robust,  hard  muscular  labor  prolonged  through  many 
hours  may  be  necessary  ;  while  in  the  feeblest  subjects  it  may  be  essential 
to  begin  with  passive  exercise  associated  with  the  least  possible  active 
exercise  ;  but  day  by  day  the  physical  exertion  can  be  increased,  and  the 
results  of  systematic  training  in  anaemic,  feeble,  gouty  persons  are  some- 
times astonishing. 

Gouty  patients  may,  for  the  purpose  of  dietetic  discussion,  be  arranged 
in  three  classes  :  first,  those  who  are  robust  and  vigorous  ;  second,  those 
who,  with  a  distinct  feebleness  of  constitution  and  sluggishness  of  habit, 
have  a  marked  tendency  to  the  accumulation  of  fat ;  third,  those  whose 
nutrition  and  general  vital  forces  are  habitually  on  a  low  level. 

In  robust  gouty  persons  it  is  essential  that  the  quantity  of  food  be 
lessened  :  such  patients  should  be  taught  to  rise  habitually  from  the  table 
with  the  appetite  not  thoroughly  satisfied.  In  the  second  class  of  patients 
some  control  over  the  appetite  is  not  rarely  imperative,  while  in  the  third 
class  of  patients  it  is  often  equally  essential  to  administer  food  beyond  the 
cravings  of  the  stomach.  As  individual  cases  occur  grading  all  the  forms 
of  the  gouty  diathesis  insensibly  one  into  the  other,  the  regulation  of  the 
quantity  as  well  as  of  the  quality  of  the  food  becomes  a  matter  to  be 
adjusted  to  the  individual  case.  There  are  certain  articles  of  food  which 
should  be  denied  to  all  gouty  subjects.  First  of  these  in  the  list  we  would 
place  cane  sugar.  The  manifest  effect  of  overindulgence  in  cane  sugar  in 
the  lithaemic  diathesis  is  probably  not  dependent  upon  any  influence  which 
it  exerts  on  the  general  system,  but  upon  the  ease  with  which  it  undergoes 
fermentation  in  the  alimentary  canal  and  gives  rise  to  acid  products.  Acid 
fruits,  including  the  tomato  and  American  strawberries,  are  also  to  be 
avoided  by  all  gouty  subjects,  while  non-acid  fruits,  if  ripe,  are  often  of 
great  service  and  may  be  taken  freely. 

In  gouty  patients  of  the  first  class  the  albuminous  principles  of  the 
food  should  be  much  decreased,  but  clinical  experience  proves  that  the 
form  in  which  the  albumin  is  taken  is  not  unimportant.  Red  meats  are 
especially  to  be  denied  ;  white  meats, — except  pork, — fish,  eggs,  and 
milk  are  to  form  the  main  staples  of  animal  food.  Chicken  is  much 
preferable  to  turkey.  Game  is  denied  by  most  authorities,  but  we  have 


26  THE  TREATMENT   OF   SYSTEMIC   STATES. 

never  seen  any  harm  from  its  use.  The  waste  muscle-products,  such 
as  kreatinin,  xanthin,  etc. ,  have  probably  some  connection  with  the  in- 
jurious effects  produced  by  red  meats.  If  this  be  so,  strong  stock  soups, 
which  contain  an  abundance  of  these  principles,  ought  to  be  injurious  ; 
and  we  have  certainly  known  of  violent  attacks  of  gout  apparently  precip- 
itated by  the  free  use  of  beef  tea,  beef  essence,  and  other  similar  stimulant 
liquids.  If  soups,  therefore,  are  employed,  they  should  be  vegetable 
rather  than  stock  soups.  Ordinarily  carbohydrates  may  be  taken  in  mod- 
eration. Green  vegetables,  including  roots,  are  especially  serviceable. 

The  proper  dietetic  treatment  of  anaemic  gouty  subjects  distinctly  in- 
clined to  corpulence  is  a  matter  of  difficult  determination.  The  first 
thought  would  lead  the  physician  to  order  a  reduction  in  the  habitual 
ingestion  of  albumin  ;  but  we  have  certainly  known  very  good  results 
produced  in  patients  of  this  class  by  lessening  very  decidedly  the  carbo- 
hydrates in  the  food.  When  this  is  done,  the  albuminous  ingestion  must 
be  increased  rather  than  decreased,  in  order  to  support  the  system.  In 
many  of  these  cases,  however,  it  will  be  found  that  the  patient  habitually 
takes  an  overplus  of  food,  and  much  good  may  be  achieved  by  lessening 
the  quantity  :  in  such  patients  the  carbohydrates  can  be  largely  withdrawn 
and  the  habitual  ingestion  of  albumin  not  increased.  It  is  especially  in 
patients  of  this  class  that  the  sagacity  of  the  physician  in  modifying  the 
diet  to  suit  the  needs  of  the  individual  will  meet  with  reward.  Our  own 
plan  has  been  in  doubtful  cases  to  make  tentative  alterations  of  the  diet, — 
to  regulate  the  quantity  of  food,  withdraw  carbohydrates,  and  order  the 
albuminous  nourishment  to  be  taken  chiefly  in  the  form  of  fish,  white 
meats,  eggs,  and  milk.  If  the  patient  improve,  the  diet  is  evidently  suit- 
able for  the  individual  case  ;  if  there  be  no  improvement,  or  if  there  be 
aggravation,  the  diet  should  be  at  once  altered. 

In  anaemic,  impoverished,  gouty  subjects  the  best  results  are  not  rarely 
to  be  achieved  by  the  employment  of  generous  diet  combined  with  the 
moderate  use  of  alcoholic  liquors.  In  selecting  the  drink,  malt  liquors 
and  acid  wines  are  to  be  avoided.  Our  own  experience  is  that  diluted 
spirits  offer  the  best  form  for  the  administration  of  alcohol. 

In  any  obstinate  gouty  case  which  fails  to  yield  to  the  ordinary  regu- 
lation of  diet  the  so-called  milk  diet  should  be  tried.  It  is  not  at  present 
possible  to  give  any  sufficient  scientific  reason  for  the  alterations  which  are 
occasionally  produced  in  diseased  human  systems  by  the  exclusive  milk 
diet.  The  whole  story  of  changes  wrought  by  the  milk  diet  in  nutrition 
•we  do  not  know.  It  evidently,  however,  has  a  pronounced  influence  upon 
primary  digestion  in  the  intestinal  tracts.  It  offers  organic  principles  in 
so  simple  a  form  as  to  reduce  to  the  minimum  the  labor  of  digestion,  and 
probably  to  relieve  greatly  the  hepatic  and  other  similar  glandular  organs 
from  excess  of  labor.  By  virtue  of  the  large  quantity  of  water  it  contains 
it  enormously  increases  the  flow  of  the  urine  and  probably  of  the  secretion 
of  the  skin,  and  in  some  cases  is  no  doubt  of  great  service  in  washing  out 
excrementitious  material  from  the  body.  Whatever  may  be  the  proper 


LITHIASIS.  27 

scientific  explanation  of  the  fact,  it  is  certain  that  in  many  cases  of  gouty 
diathesis  and  in  various  other  abnormal  conditions  of  nutrition  an  exclu- 
sive milk  diet  is  extremely  beneficial.  Thus,  in  fatty  anaemic  subjects  a 
course  of  two  or  three  weeks  of  milk  diet  sometimes  alters  the  nutrition 
so  that  afterwards  feeding  and  tonics  produce  effects  which  were  previously 
not  attainable.  We  have  always  suspected  that  in  these  patients  there  is  an 
underlying  gouty  diathesis.  We  have  seen  many  cases  of  gouty  disease 
of  a  chronic  and  subacute  type  in  which  remedial  measures  had  entirely 
failed,  but  which  yielded  easily,  though  slowly,  to  an  exclusive  milk  diet. 
Very  frequently  when  it  is  simply  intended  to  fatten  the  patient,  or  in  the 
combating  of  the  gouty  diathesis,  milk  is  given  largely  with  other  food  ; 
but  to  get  the  peculiar  full  effects  of  a  milk  diet  it  is  essential  that  the 
patient  abstain,  at  least  for  a  time,  from  all  other  food.  After  two  or  three 
weeks  oatmeal  or  cracked  wheat  or  stale  bread  may  be  allowed,  then 
green  vegetables,  and  slowly  the  patient  may  thus  be  restored  to  ordinary 
diet.  In  severe  cases,  however,  milk  diet  may  be  persisted  in  for  weeks, 
and  it  is  possible  for  the  human  adult  to  work  laboriously  and  live  ex- 
clusively upon  milk.  In  order  to  afford  sufficient  nitrogenous  nutriment, 
from  five  to  seven  pints  of  milk  a  day  must  be  taken.  This  amount  of 
milk  contains  too  much  fat  for  the  needs  of  the  system  :  it  should  there- 
fore be  skimmed.  The  so-called  skimmed  milk  sold  from  creameries  is, 
however,  not  suitable,  because  the  fat  has  been  too  absolutely  withdrawn 
from  it,  and  because  it  is  usually  not  so  fresh  as  is  desirable.  The  skim- 
ming of  the  milk  should  not  be  too  close.  It  is  essential  that  the  milk 
be  taken  at  intervals  of  not  longer  than  two  hours,  and  that  it  be  drunk 
by  sipping  rather  than  by  gulping,  so  as  to  avoid  any  danger  from  the 
formation  of  hard  clots  in  the  stomach.  When  the  digestion  is  good  the 
milk  may  be  taken  cold.  When  the  digestion  is  very  feeble  it  should  be 
taken  hot.  But  boiled  milk  should  not  be  employed,  as  it  is  of  more 
difficult  digestion  than  is  unboiled  milk.  During  the  progress  of  the 
milk  course  constipation  is  almost  invariably  present :  this  must  be  over- 
come by  the  administration  of  drugs.  In  gouty  subjects  saline  laxa- 
tives are  preferable. 


CHAPTER    III. 

CALORIC. 

THERE  are  two  conditions  of  the  force  caloric,  spoken  of  as  distinct 
entities,  but  which  are  merely  relative  terms,  expressive  of  the  presence 
of  an  excess  or  of  the  absence  of  the  normal  amount,  or,  more  strictly 
speaking,  normal  intensity  of  the  force.  Cold  and  heat,  in  connection 
with  the  human  body,  respectively  mean  an  intensity  of  caloric  below  and 
above  98.5°  F. 

USE    OF    HEAT. 

LOCAL   USE   OF    HEAT. 

The  continuous  application  of  moist  heat  acts  as  a  relaxant  to  the  sur- 
face of  the  body,  producing  probably  a  local  congestion  and  exerting  the 
influence  of  a  slow  counter-irritation.  It  is  often  practised  with  advan- 
tage in  cases  of  sprains  and  internal  inflammation. 

The  local  use  of  an  intense  dry  heat  has  recently  been  shown  to  be 
very  advantageous  in  various  local  disorders  of  the  limbs,  and  even  of  the 
trunkal  muscles.  For  the  purpose  there  are  upon  the  market  various 
forms  of  apparatus  which  agree  in  the  general  principle  that  the  heat  is 
chiefly  applied  by  means  of  superheated  air  in  a  small  chamber,  with  pro- 
vision by  means  of  ventilators  and  other  devices  for  the  removal  of  the 
moisture  that  comes  from  the  skin.  When  proper  care  is  exercised  with 
an  efficient  apparatus  the  degree  of  heat  that  is  borne  without  suffering  is 
very  remarkable.  We  have  frequently  carried  the  temperature  up  to 
340°  F.  If,  however,  under  these  circumstances  any  moisture  collects 
upon  the  surface  of  the  part,  blistering  results.  With  most,  if  not  all, 
forms  of  apparatus  the  parts  should  be  lightly  wrapped  in  patent  lint.  A 
temperature  below  240°  F.  is  rarely  of  service.  In  most  cases,  however, 
it  is  better  to  use  in  the  beginning  a  lower  temperature  at  one  or  two 
stances,  partly  for  moral  reasons  and  partly  because  the  skin  is  often  at 
first  very  sensitive,  although  it  rapidly  becomes  accustomed  to  the  higher 
temperatures.  The  duration  of  the  application  of  the  heat  varies  from  ten 
to  forty  minutes. 

We  know  of  no  experimental  evidences  as  to  the  exact  effect  of  this 
high  temperature  upon  the  affected  joint.  The  fact,  however,  that  the 
general  bodily  temperature  may  be  raised  three  or  even  four  degrees  is 
evidence  that  there  is  a  great  absorption  of  heat,  and  that  there  probably 
is  a  local  heating  far  above  the  highest  fever  point.  Moreover,  a  distinct 
enlargement  often  occurs  in  the  heated  part,  so  that  there  must  be  an 
28 


GENERAL  EMPLOYMENT  OF  HEAT.        29 

excess  of  blood  drawn  to  it.  Probably  both  the  circulation  and  the 
chemical  movements  in  the  joint  are  greatly  accelerated.  Certainly  a  re- 
markable absorption  of  exudates  often  occurs.  We  have  frequently  seen 
an  acute  attack  of  gout  precipitated  by  the  application  to  a  long-diseased 
joint  about  which  there  was  much  exudation.  This  acute  attack  has  often 
been  accompanied  by  a  very  perceptible  lessening  of  the  exudate  :  we 
believe  such  attacks  to  be  due  to  the  absorption  into  the  blood  of  gouty 
acids  or  salts  which  had  been  liberated  from  the  tissues  of  the  joint. 

Although  this  method  of  treatment  was  first  brought  forward  for  the 
cure  of  rheumatism,  there  is  a  priori  no  reason  for  supposing  that  it  can 
especially  affect  the  general  rheumatic  condition,  much  less  the  rheumatic 
diathesis,  unless  the  patient  be  well  wrapped  up  in  blankets  and  the  local 
heat  be  used  as  a  general  sudorific  measure,  when  whatever  relief  a  free 
sweating  can  produce  may  be  obtained.  On  the  other  hand,  the  method 
is  of  very  great  value  in  the  treatment  of  local  inflammatory  conditions 
with  exudation,  whether  these  be  or  be  not  of  rheumatic  origin.  In  sub- 
acute  and  chronic  t<znia  synovitis,  in  chronic  sprains,  in  acute  sprains 
when  there  is  no  severe  acute  inflammation  or  when  this  has  been  subdued 
by  treatment,  and  in  various  forms  of  synovitis  dry  heat  is  of  great  service. 
Its  effects  are  much  more  prompt  and  marked  in  cases  of  small  than  of 
large  joints.  Thus,  it  is  much  more  serviceable  when  the  ankle  rather 
than  the  knee  is  affected,  the  result  probably  being  due  to  the  inability 
of  the  application  to  rais  uniformly  to  a  high  point  the  temperature  of  a 
large  joint.  In  rheumatic  cases  the  method  should  be  employed  only  as 
an  aid  to  the  general  treatment  of  the  condition. 

GENERAL  EMPLOYMENT  OF  HEAT. 

The  phenomena  of  death  from  cold  show  that  a  lack  of  caloric  in  the 
body  is  no  less  paralyzant  of  animal  functions  than  is  an  excess  of  the 
same  force.  Evidently  the  organism  was  constructed  to  run  upon  a  cer- 
tain plane  of  heat,  and  cannot  vary  from  this  without  serious  results.  By 
numerous  experiments  upon  animals  H.  C.  Wood  has  proved  that  in  a 
cool  apartment  death  rapidly  results  after  section  of  the  spinal  cord,  from 
falling  of  the  bodily  temperature,  the  animal  which  in  a  warm  room  will 
live  indefinitely  dying  very  shortly  in  a  temperature  of  forty  degrees.  The 
cause  of  the  inability  of  the  animal  to  resist  external  cold  after  section  of 
the  cord  is  undoubtedly  vaso-motor  paralysis.  Normally,  the  tempera- 
ture of  the  interior  of  the  body  is  maintained  by  keeping  an  outer  layer  of 
partially  cooled  tissue  between  the  internal  organs  and  tissues  and  the 
outer  air.  When  the  power  of  contracting  the  superficial  vessels  has  been 
lost,  the  organism  can  no  longer  maintain  this  protecting  layer,  the  sur- 
face-temperature rises  to  that  of  the  interior,  heat  is  rapidly  lost,  and  the 
whole  body  is  uniformly  cooled. 

Vaso-motor  paralysis  is  produced  by  toxic  doses  of  various  remedies, 
and  under  these  circumstances  artificial  maintenance  of  the  bodily  tem- 
perature is  imperative,  forming  a  very  important  portion  of  the  treatment 


30  CALORIC. 

of  all  such  poisoning.  Collapse  from  any  cause  is  largely  dependent  upon, 
or,  more  correctly  speaking,  largely  is,  vaso-motor  palsy  ;  hence  in  almost 
all  forms  of  collapse  the  use  of  external  heat  is  of  great  importance. 

The  late  Charles  Hunter  very  successfully  applied  this  treatment  to 
that  form  of  collapse  which  follows  injuries  and  surgical  operations  and  is 
known  by  surgeons  as  shock.  The  lack  of  power  of  alcoholic  and  other 
ordinary  stimulants  in  this  condition  is  proverbial.  The  pathological  state 
is  undoubtedly  vaso-motor  palsy,  the  bodily  temperature  is  much  below 
normal,  and  the  rational  treatment  consists  in  the  hypodermic  use  of 
atropine  and  digitalis  and  the  external  employment  of  the  hot  bath.  We 
believe  this  plan  of  treatment  to  be  a  most  important  addition  to  surgical 
therapeutics.  In  the  first  days  of  post-fcetal  life  the  power  of  resisting 
external  cold  is  very  slight,  and  in  many  cases  of  still-born  children,  or  of 
children  whose  vital  powers  are  almost  extinguished  at  birth,  life  may  be 
saved  by  a  high  external  temperature,  the  little  waif  being  kept  in  an  air 
of  98°  F. ,  and  also  away  from  the  influence  of  cold  walls  and  articles 
which  would  draw  off,  as  it  were,  the  slender  store  of  heat  provided  by 
nature,  radiation  being  greatly  affected  by  the  temperature  of  surrounding 
objects. 

It  is  hardly  necessary  to  dwell  in  greater  detail  upon  the  various  forms 
of  collapse.  Enough  has  been  said  to  illustrate  the  principle  that,  -when- 
ever the  bodily  temperature  falls  below  normal,  pyretic  treatment  is  de- 
manded. The  vigor  of  the  treatment  should  always  be  in  direct  propor- 
tion to  the  suddenness  and  extent  of  the  fall  of  temperature. 

In  regard  to  the  methods  of  applying  heat,  it  must,  in  the  first  place, 
be  understood  that  wrapping  in  blankets,  etc.,  merely  prevents  cool- 
ing of  the  body,  and  when  the  animal  temperature  has  already  fallen  it 
will  not  suffice  at  all.  The  same  may  be  said  of  air  heated  to  tempera- 
tures which  can  be  readily  obtained  or  can  be  continuously  borne  by  the 
attendants.  Radiated  heat  is  somewhat  better,  and  often  the  use  of  a 
brisk  open  fire  is  of  service.  The  hot  bath  is,  however,  the  only  pyretic 
remedy  that  can  be  relied  on.  It  should  always  be  a  full  bath,  in  as  warm 
a  room  as  can  be  procured,  and  should  be  at  a  temperature  of  about  104° 
F.  when  the  patient  is  put  into  it.  The  duration  of  the  bath  must  vary 
with  the  circumstances  of  the  case.  It  should  not  be  less  than  half  an 
hour,  unless  the  mouth-temperature  sooner  become  normal.  During  the 
bath  the  heat  of  the  water  should  steadily  be  increased  as  fast  as  it  can  be 
borne  if  the  patient  be  conscious,  or,  if  he  be  unconscious,  until  a  tem- 
perature of  110°  F.  is  reached. 

USE   OF    COLD. 

LOCAL    EMPLOYMENT   OF   COLD. 

When  cold  is  applied  persistently  to  any  part,  it  acts  as  a  direct  and 
very  powerful  depressant,  of  varying  power  according  to  its  intensity.  It 
is,  therefore,  used  locally  to  reduce  inflammation,  especially  when  the 


LOCAL  EMPLOYMENT  OF  COLD.         31 

latter  is  of  an  active  type.  In  this  employment  of  cold,  care  must  be 
exercised  not  to  carry  its  use  too  far,  lest  it  suspend  all  nutritive  actions 
and  interfere  with  those  processes  of  repair  which  almost  always  form  a 
part  of  inflammation.  Indeed,  it  is  possible  to  convert  an  inflammation 
into  gangrene  by  the  too  energetic  employment  of  this  agency.  Locally, 
cold  is  generally  applied  by  means  of  cold-water  compresses,  irrigation 
with  cold  water,  and  the  application  of  pounded  ice,  either  enclosed  in 
india-rubber  bags  or  in  bladders,  or  in  the  form  of  the  ice-poultice*  It  is 
very  doubtful  whether  the  use  of  "freezing  mixtures"  is  ever  justifiable 
in  inflammation.  The  effects  of  the  cold  in  individual  cases  are  to  be 
judged  of  by  the  alterations  in  the  heat  and  redness  of  the  part.  The 
local  employment  of  cold  belongs  for  the  most  part  within  the  province 
of  the  surgeon,  but  the  remedy  is  of  great  value  in  certain  diseases.  In 
diphtheria  and  in  anginose  scarlatina  very  great  benefit  may  be  obtained 
by  enveloping  the  throat  over  the  tonsils  with  powdered  ice  enclosed  in 
bladders,  in  pieces  of  pigs'  intestines  such  as  are  used  by  sausage-makers, 
or  in  thin  india-rubber  bags. 

In  internal  trunkal  inflammations,  such  as  pneumonia  and  pleurisy, 
the  application  of  cold  by  wet  compresses  or  of  ice-bags  over  the  diseased 
organ  has  been  employed  extensively  in  Germany  for  many  years,  and 
has  steadily  maintained  its  reputation.  It  is  especially  serviceable  when 
there  is  a  tendency  to  general  high  temperature,  and  is  probably  even 
more  useful  in  the  catarrhal  pneumonia  of  children  than  in  adult  cases. 

In  meningitis  the  great  value  of  the  application  of  ice  to  the  shaven 
scalp  is  undeniable,  and  vn.  peritonitis  we  have  seen  very  great  relief  afforded 
by  the  use  of  cold,  as  recommended  by  Abercrombie,  Niemeyer,  and 
others.  As  is  the  case  in  pneumonia,  warm  poultices  are  more  generally 
viewed  with  favor  in  peritonitis  by  the  profession  in  this  country.  We  have 
frequently  used  them  with  excellent  effect,  and  in  at  least  one  instance 
after  ice-poultices  had  been  employed.  In  this  case  the  cold  applica- 
tions were  at  first  very  agreeable  to  the  patient,  as  were  the  warm  poul- 
tices afterwards,  and  the  good  achieved  seemed  to  be  in  accord  with  the 
sensations  of  the  patient.  It  seems  to  us  a  good  clinical  rule  to  select  the 
ice  or  the  warm  poultice  according  to  the  feelings  of  the  patient.  Early  in 
the  attack,  when  the  fever  is  high,  the  ice  will  generally  be  the  more  useful. 

In  using  cold  for  the  purpose  of  combating  inflammation,  the  appli- 
cation must  be  kept  up  until  the  desired  effect  is  produced.  When  em- 
ployed intermittently,  cold  even  becomes  a  stimulant,  the  reaction  which 
follows  its  first  impression  being  greater  than  its  direct  effects.  Hence  the 
cold  douche  has  been  used  with  asserted  advantage  as  a  stimulus  to 
sluggish  ulcers. 

It  seems  proper  here  to  direct  attention  to  the  statements  of  Fr. 
Mosler,1  that  the  application  of  cold  water  to  the  abdomen  produces  con- 
traction of  the  spleen,  and  that  the  cold  douche  applied  for  two  or  three 

*  Made  by  mixing  finely  broken  ice  with  dry  Indian  meal  or  fine  sawdust. 


32  CALORIC. 

minutes  and  repeated  at  longer  or  shorter  intervals  very  sensibly  affects 
the  enlarged  spleen  of  intermittent  or  typhoid  fever,  and  even  of  such 
chronic  diseases  as  leukaemia,  in  which  class  of  cases  the  application  should 
usually  be  made  twice  a  day. 

COLD    AS    A    TONIC    AND   STIMULANT. 

Almost  every  one  has  experienced  the  exhilaration  of  the  reaction 
which,  in  a  healthy  person,  follows  the  sudden  dash  of  a  cold  shower-bath 
or  the  plunge  into  a  mass  of  cold  water.  The  researches  of  Liebermeister, 
which  will  be  detailed  hereafter,  prove  that  a  cold  bath,  when  of  not  too 
long  duration,  actually  increases  the  oxidation  of  tissue  to  such  a  degree 
as  to  elevate  the  temperature  of  the  body.  When  cold  bathing  is  em- 
ployed as  a  tonic,  the  first  principle  to  be  borne  in  mind  is  that  the  bath 
should  not  be  too  severe  or  too  long  continued,  else  it  becomes  a  direct 
depressant,  debilitating  and  lowering  the  temperature  of  the  bather. 
When  the  subject  has  sufficient  vital  power  to  react  after  the  bath,  sea- 
bathing is  often  of  very  great  service,  but  in  debilitated  persons  it  may 
produce  serious  exhaustion,  partly  by  the  fatigue  induced  and  partly  by 
the  excessive  abstraction  of  heat  from  the  body.  The  cold  bath,  when 
not  followed  by  a  healthy  reaction,  is  anything  but  a  tonic. 

COLD    IN    PYREXIA. 

The  use  of  cold  in  fever  is  no  new  thing  :  employed  by  Galen,  used  not 
infrequently  during  the  last  century,  first  systematized  and  insisted  upon 
by  Currie,  cold  bathing  in  fever  was  brought  before  the  world  as  a  really 
new-born  measure  by  Brandt,  of  Stettin,  and  received  the  seal  of  perma- 
nent usefulness  from  the  scientific  clinical  labors  of  Jiirgensen  at  Kiel. 

The  consideration  of  the  method  naturally  divides  itself  into, — first,  a 
study  of  its  physiological  action  ;  secondly,  an  investigation  as  to  its  clin- 
ical value  ;  and  thirdly,  a  more  particular  account  of  its  effect,  the  cases 
to  which  it  is  best  adapted,  and  the  method  of  its  application.  Moreover, 
there  are  two  distinct  forms  of  pyrexia,  which  may  be  termed  the  acute 
and  the  chronic,  and  which  are  best  considered  separately. 

ACUTE  PYREXIA. — If  the  following  propositions  be  true,  caloric  in 
excess  acts  as  a  direct  poison  to  the  body,  and  the  phenomena  of  severe 
acute  fever  are  largely  due  to  the  heat  itself.  The  proofs  of  the  proposi- 
tions are  given  very  briefly  after  them.* 

First.  External  heat  applied  to  the  body  of  the  normal  animal,  so  as 
to  elevate  the  temperature,  produces  derangements  of  the  nervous  system, 
of  the  circulation,  etc. ,  precisely  similar  to  those  seen  in  natural  fever,  the 
intensity  of  the  disturbance  being  directly  proportionate  to  the  rise  in 
temperature. 

Second.   Heat  applied  locally  to  the  brain  or  to  the  heart  produces  in 

*  Want  of  space  prevents  the  elaboration  of  this.  The  unconvinced  reader  is  respect- 
fully referred  to  the  treatise  of  H.  C.  Wood  on  Thermic  Fever,  and  his  Toner  Lecture 
on  Fever. 


COLD   IN    PYREXIA.  33 

the  functions  of  the  organ  those  disturbances  which  are  familiar  phenomena 
of  fever,  the  intensity  of  the  disturbance  being  directly  proportionate  to 
the  excess  of  heat  in  the  organ. 

Third,  The  withdrawal  of  the  excess  of  heat  in  fever  is  followed  by  a 
relief  of  the  nervous  and  circulatory  disturbances. 

When  a  dog,  cat,  or  rabbit  is  shut  up  in  a  box,  as  in  the  experiments 
of  H.  C.  Wood,  heated  either  by  the  sun's  rays  or  by  artificial  means, 
the  temperature  of  the  animal  rises,  and  at  the  same  time  the  pulse-rate 
becomes  part  passu  more  rapid,  the  breathing  grows  more  and  more 
hurried,  and  the  restless,  uneasy  movements  of  the  victim  show  the 
general  distress  it  is  suffering.  As  the  temperature  increases,  the  nervous 
disturbance  becomes  more  and  more  apparent ;  and  stupor,  coma,  partial 
paralysis,  convulsions,  and  finally  death  by  arrest  of  the  respiration  occur. 
These  phenomena  sometimes  come  on  gradually,  but  sometimes  are  de- 
veloped suddenly.  The  temperature  at  which  death  occurred  in  these 
experiments  varied  in  the  rabbit  from  in0  to  114.5°  F-  >'  m  tne  dog  ^ 
was  about  111°  F.  In  man  a  similar  series  of  phenomena  are  developed 
by  exposure  to  excessive  heat,  although,  owing  to  his  extraordinary 
power  of  cooling  his  body  and  of  protecting  it  against  cold,  he  is  able  to 
bear  extremes  of  temperature  far  beyond  the  points  which  would  prove 
fatal  to  any  given  species  of  animals.  Yet  when  his  body  is  heated  the 
results  are  the  same,  as  is  proved  by  the  terrible  mortality  of  sunstroke. 

"To  prove  the  second  proposition,  I"  [H.  C.  Wood]  "caused  hot 
water  to  flow  through  pigs'  bladders  fitted  as  a  sort  of  bonnet  to  the  heads 
of  cats  and  rabbits.  It  is  evident  that  with  small  animals  we  can  in  this  way 
heat  the  brain  without  heating  materially  the  remainder  of  the  body.  It 
was  found  that  coma,  with  or  without  convulsions,  was  produced.  Some- 
times the  stupor  came  on  gradually,  hebetude  slowly  deepening  into  coma, 
but  in  other  instances  unconsciousness  was  developed  very  suddenly.  It 
was  also  found  that  severe  nervous  symptoms  and  death  were  produced 
when  the  brain  reached  the  temperature  which  was  fatal  to  the  animal  in  the 
hot  box.  Without  occupying  more  space,  the  conjoint  labors  of  Lauder 
Brunton  and  Liebermeister  have  proved  that  the  accelerated  pulse 
in  fever  is  largely  due  to  the  action  of  the  heat  upon  the  heart  and  its 
nerves  :  so  that  the  second  proposition  may  be  considered  demonstrated. 

"  In  regard  to  the  third  proposition,  I  have  frequently  taken  animals 
out  of  the  hot  box  perfectly  unconscious  and  plunged  them  into  a  bucket 
of  cold  water,  have  watched  the  temperature  of  the  water  rise  while  that  of 
the  animal  fell,  and  as  the  bodily  heat  came  towards  normal  have  seen  the 
coma  disappear,  so  that  within  ten  minutes  the  at  first  absolutely  comatose 
and  dying  rabbit  would  be  skipping  about  on  the  grass.  I  have  placed  a 
man  whose  temperature  was  nearly  110°  F. ,  who  was  unconscious,  with  a 
feeble  running  pulse  of  160  or  170,  irregular,  jerking,  slow  respirations, 
and  every  indication  of  immediate  death,  in  a  bath  of  60°  F. ,  and  within 
a  minute  and  a  half  have  seen  consciousness  partially  restored,  and  in 
another  minute  and  a  half  the  man  trying  to  get  out  of  the  bath.  What 

3 


34  CALORIC. 

could  the  bath  do  to  affect  the  man  so  profoundly  and  so  quickly  but  with- 
draw the  heat  ?  That  the  heat  was  present,  and  that  it  was  withdrawn, 
the  thermometer  proved.  If  the  drowsiness  had  been  due  to  simple  con- 
gestion of  the  brain,  very  certainly  would  the  bath,  by  driving  the  blood 
from  the  surface,  have  increased  the  trouble.  It  must  be  borne  in  mind 
that  this  case  is  by  no  means  unparalleled  :  similar  instances  of  the  good 
effects  of  the  sudden  withdrawal  of  heat  in  rheumatic  hyperpyrexia  have 
been  recorded  by  both  English  and  German  observers,  and  recent  Con- 
tinental literature  is  full  of  reports  of  the  relief  of  nervous  symptoms  in 
various  pyrexias  by  the  abstraction  of  heat. 

' '  Finally,  as  excessive  heat  is  present  in  fever,  as  excessive  heat,  when 
present,  is  not  only  able,  but  is  forced,  so  to  speak,  by  its  own  attributes, 
to  produce  disturbance  of  the  functions  of  innervation  and  circulation, 
and  as  the  withdrawal  of  the  excessive  heat  in  fever  is  followed  by  instan- 
taneous relief  of  the  symptoms  of  disturbed  innervation  and  circulation, 
surely  the  conclusion  is  logically  inevitable  that  excessive  temperature  is 
the  chief  cause  of  the  other  symptoms  of  fever,  and  that  in  acute  pyrexia 
threatening  life  the  heat  should  be  withdrawn  as  rapidly  as  possible  by 
means  of  the  cold  bath." 

CHRONIC  PYREXIA. — The  effects  of  a  long-continued  pyrexia,  not  suffi- 
ciently intense  to  induce  immediate  serious  symptoms,  upon  the  structure 
of  the  various  tissues  have  been  elaborately  investigated  by  Liebermeister,1 
who  found  that  the  liver,  spleen,  kidneys,  voluntary  and  involuntary 
muscles,  blood-vessels,  and  even  the  nerve-centres  undergo  a  granular 
degeneration  during  the  continued  pyrexia.  The  lesion  was  constantly 
present  in  the  bodies  of  those  who  had  suffered  in  this  way  during  life, 
entirely  independently  of  the  nature  of  the  primary  disease.  In  cases  of 
infectious  fever  in  which  the  temperature  had  never  been  high,  this  gran- 
ular degeneration  did  not  exist.  Previous  to  the  investigation  of  Lieber- 
meister,  Zenker  had  demonstrated  that  the  muscles  undergo  a  peculiar 
granular  degeneration  in  typhoid  and  other  fevers  ;  and  the  fact  has  been 
abundantly  attested  by  later  observers.  We  do  not  know  that  the  observa- 
tions of  Liebermeister  as  to  the  occurrence  of  this  lesion  in  non-infectious 
pyrexia  have  been  confirmed,  but  we  have  no  doubt  of  their  correctness. 

It  is  evident  that  in  all  fevers  a  primary  therapeutic  indication  is  to  reduce 
the  temperature.  Of  course,  if  possible,  this  should  be  done  by  checking 
the  excessive  production  of  heat ;  but,  unfortunately,  this  often  lies  out  of 
our  power,  and  we  are  forced  to  abstract  the  heat  by  mechanical  means. 

It  is  a  priori  impossible  to  determine  what  effect  upon  the  production 
of  heat  the  rapid  abstraction  of  it  would  have,  but,  from  the  well-known 
powers  of  the  organism  to  resist  external  cold,  it  seems  probable  that  the 
heat-production  would  be  increased  rather  than  diminished  by  the  abstrac- 
tion of  caloric.  An  experimental  study  of  this  problem  has  been  made 
by  several  observers,  but  with,  unfortunately,  different  results.  Weis- 
flog*  has  found  that  the  local  abstraction  of  heat  by  a  cold  sitz-bath 
causes  a  rise  in  the  temperature  of  the  axilla,  and  that  in  fever-patients, 


COLD   IN   PYREXIA.  35 

unless  the  sitz-bath  is  prolonged  over  twenty-minutes,  no  fall  of  the  bodily 
temperature  results.  In  1860  Kernig4  found  that  a  healthy  man  in  a 
bath  of  the  temperature  of  from  28°  to  30°  C.  produces  about  twice  as 
much  heat  as  normal ;  in  a  bath  of  24°  C. ,  about  three  times  as  much  ; 
and  in  a  bath  of  20°  C.,  about  four  times  as  much.  Liebermeister 5 
found  that  in  a  healthy  man  exposure  to  cold  for  a  brief  period  of  time 
causes  a  rise  in  the  bodily  temperature,  and  on  extending  his  researches 
into  fever  proved  that  where  the  external  cooling  was  not  too  powerful 
or  too  long  continued  the  same  was  true  of  fever-patients.  From  this  it 
follows  that  the  use  of  external  cold  stimulates  heat-production.  This, 
to  our  minds,  has  been  confirmed  by  the  chemical  researches  of  J.  Gilde- 
meister,6  of  Lehmann,T  and  of  Liebermeister8  himself  upon  men,  and  by 
those  of  A.  Roehrig  and  N.  Zuntz9  upon  animals,  all  of  which  show 
that  both  in  health  and  in  fever  very  much  more  carbonic  acid  than  nor- 
mal is  eliminated  under  exposure  to  cold.  This  would  appear  to  prove 
that  cold  baths  increase  the  production  of  animal  heat.  It  seems  most 
probable  that  this  is  the  case  ;  but  A.  Murri  believes  that  he  has  proved 
that  the  cold  baths  have  no  such  influence.*  At  any  rate,  the  investiga- 
tions of  Liebermeister  and  others  have  shown  that  the  first  rise  of  tem- 
perature produced  alike  in  healthy  and  in  fever  subjects  by  exposure  to  a 
moderate  and  not  too  long  continued  cold  is  followed  after  removal  of  the 
cold  by  a  fall  of  bodily  temperature  of  greater  or  less  degree.  While, 
therefore,  external  cold  probably  first  stimulates,  it  afterwards  depresses  the 
production  of  animal  heat.  The  further  experiments  of  Liebermeister8 
upon  the  elimination  of  carbonic  acid  are  also  in  accord  with  his  tem- 
perature-study, for  he  found  that  after  the  bath  the  elimination  sank 
below  normal,  and  so  continued  for  a  considerable  period. 

If  the  cold  bath  really  affects  the  fever-process,  it  ought  distinctly  to 
reduce  the  excretion  of  urea.  That  it  has  this  action  would  seem  to  be 
proved  by  the  research  of  Sassetzky , 10  who  found  that  the  continuous  use 
of  the  cold  bath  invariably  lessened  the  urinary  elimination  of  nitrogenous 
material  and  of  the  phosphates,  although  it  increased  the  total  flow  of 
urine.  The  subject  is,  however,  a  very  difficult  one,  chiefly  because  it  is 
almost  impossible  to  know  in  any  individual  case  what  the  elimination  of 
urea  would  have  been  if  no  baths  had  been  used.  Bauer  and  Kiinstle  " 
gave  to  the  patients  cold  baths  upon  alternate  days,  and  found  that  the 
excretion  of  urea  was  in  each  case  greater  on  the  days  when  baths  were 
used  than  on  those  on  which  they  were  not  employed.  These  experi- 
ments have  been  quoted  as  showing  that  the  cold  bath  increases  the  ex- 
cretion of  urea,  but  in  Schleich's12  investigations  on  the  effects  of  hot 
baths  the  increase  of  the  excretion  of  urea  frequently  did  not  show  itself 
until  the  day  after  the  bath.  It  is  probable,  therefore,  as  believed  by 
Schleich,  that  the  destruction  of  albuminous  substance  in  the  tissues  is 


*  We  have  never  seen  the  brochure  of  A.  Murri  {Del  Potere  regulatore  della  Tem- 
Peratura  animate,  Firenze,  1873).    It  is  abstracted  in  the  London  Medical  Record,  vol.  i. 


36  CALORIC. 

not  manifested  in  urea-elimination  until  after  twenty-four  hours,  or,  in 
other  words,  that  twenty-four  hours  are  necessary  for  the  completion  of 
the  formation  and  the  excretion  of  urea:  so  that  if  the  baths  are  used,  for 
example,  on  Monday  the  urinary  solids  will  indicate  their  effects  not  on 
the  same  day  but  on  Tuesday.  If  this  be  correct,  the  experiments  of 
Bauer  and  Kunstle  are  in  accord  with  those  of  Sassetzky  in  showing  that 
the  cold  bath  lessens  the  formation  of  urea  in  fever. 

During  the  bath  the  pulse  of  the  fever-patient  usually  becomes  much 
smaller  and  harder,  and  the  sphygmographic  tracings  made  by  Winter- 
nitz  before  and  after  the  use  of  the  cold  bath  (if  tracings  of  this  kind  can 
be  trusted)  indicate  that  there  is  after  the  cold  bath  greatly  increased 
arterial  tonus.  (See  Verhandl.  des  Congr.  fur  Innere  Med. ,  1886.)  It 
may  be  that  the  good  obtained  by  the  cold  bath  is  really  due  to  a  reflex 
action  upon  the  nerve-centres,  and  is  not  entirely  the  result  of  the  with- 
drawal of  the  heat.* 

The  results  of  the  physiological  study  of  the  effects  of  cold  in  fever 
may  be  summed  up  as  follows.  During  a  sufficiently  prolonged  applica- 
tion of  cold  the  bodily  temperature  falls,  although  an  increased  production 
of  heat — i.e.,  consumption  of  tissue — at  first  occurs.  After  the  applica- 
tion, the  bodily  temperature  continues  to  fall,  or  but  slowly  regains  its 
former  position  :  the  present  evidence  at  our  disposal  indicates,  but  is  not 
sufficient  to  prove,  that  this  slow  regaining  of  bodily  temperature  is  due  to 
a  diminished  production  of  animal  heat, — that  is,  to  a  decrease  in  the 
waste  of  tisszie  and  in  the  formation  of  urea  and  carbonic  acid. 

When  the  use  of  cold  in  fever  was  first  recommended  in  this  work 
the  method  was  looked  upon  with  disfavor  by  so  many  medical  practi- 
tioners, especially  in  the  United  States,  that  it  seemed  necessary  to  discuss, 
carefully  and  in  detail,  the  statistics  of  the  subject  to  show  that  these  were 
sufficiently  large  to  be  decisive,  and  were  sufficiently  plain  in  their  teaching 

*  Naunyn  (Archiv  f.  Exper.  Path,  und  Pharm.,  1884,  Bd.  xviii.,  Heft  i  and  2), 
indeed,  denies  that  the  good  achieved  is  due  to  withdrawal  of  heat  at  all.  In  his 
experiments  he  found  that  if  he  maintained  proper  ventilation,  carefully  giving  fopd  and 
water,  he  could  gradually  heat  rabbits  up  to  the  temperature  of  107°  and  108°  F.,  and 
keep  them  at  this  temperature  for  weeks  without  their  evidencing  any  inconvenience 
and  without  the  production  of  any  internal  lesions.  Krishaber  was  also  able  to  maintain 
in  a  dry  room  117°  F.,  his  own  temperature  reaching  107°,  pulse  85,  respiration  35. 
Naunyn,  as  the  result  of  his  experience,  is  a  very  strong  advocate  of  the  employment  of 
frequent  baths  in  the  treatment  of  fever,  but  believes  that  they  act  by  indirectly  reducing 
bodily  waste  and  increasing  renal  secretion,  strengthening  the  pulse,  and  stimulating  the 
nerve-centres.  L.  Schweinburg  and  C.  Pollak  ( Centralbl.  f.  Gesam.  Therap.,  March, 
1887)  have  found  in  a  series  of  apparently  very  careful  experiments  that  cold  hip-baths 
notably  increase  blood-pressure  and  lessen  pulse-rate,  while  hot  hip-baths  have  the  oppo- 
site effect.  Naunyn  believes  that  better  results  are  obtained  from  the  use  of  constant 
lukewarm  baths  than  from  the  employment  of  excessively  cold  baths.  In  very  severe 
cases,  marked  by  dicrotic  pulse  and  disturbance  of  the  sensorium,  the  bath  treatment, 
according  to  Naunyn,  should  be  commenced  before  the  axillary  temperature  reaches 
103°  F.,  and  frequently  a  warm  bath  may  in  such  case  be  given  between  two  cold  baths. 
Such  a  treatment  is  especially  indicated  when  there  is  marked  delirium,  tremor,  subsul- 
tus  tendinum,  or  great  restlessness ;  a  warm  bath  in  the  evening  then  seldom  fails  to 
produce  some  favorable  result. 


COLD    IN    PYREXIA.  37 

to  demonstrate  the  value  of  the  practice.  As,  however,  at  present  almost 
all  medical  authorities  are  in  accord  in  recommending  the  early  use  of  cold 
in  pyrexia,  we  have  omitted  from  the  present  edition  these  statistics,  and 
would  refer  any  doubtful  student  to  the  ninth  edition  of  this  work,  page  63. 

The  cold-water  treatment  has  been  employed  upon  a  large  scale,  espe- 
cially in  typhus  and  typhoid  fevers,  but  there  can  be  no  doubt  of  its  value 
in  scarlet  fever,  in  diphtheria,  septic&mia,  and  other  germ  diseases  accom- 
panied by  high  bodily  temperature.  In  diphtheria  or  anginose  scarlatina 
the  general  use  of  cold  may  often  with  great  advantage  be  combined  with 
a  local  application  of  the  ice-bag  or  the  ice-poultice  to  the  throat.  During 
the  summer  months  serous  diarrhoea  {cholera  infantuni],  in  some  of  its 
forms,  annually  destroys  large  numbers  of  children  in  this  country.  In 
most  of  these  cases  the  bodily  temperature  is,  first  or  last,  much  elevated, 
and  the  diarrhoea  is  produced  and  maintained  by  the  heat,  as  originally 
pointed  out  by  Comegys.13  All  the  ordinary  methods  of  drug-adminis- 
tration frequently  fail,  or,  at  most,  succeed  only  in  keeping  the  child 
alive  until  the  heat  of  the  weather  subsides.  Under  these  circumstances, 
antipyretic  treatment  acts  in  a  magical  manner.  Usually  simple  bathing 
in  water  of  about  75°  F. ,  at  intervals  of  from  three  to  six  hours,  will  be 
found  sufficient,  but  in  some  cases  the  plan  recommended  by  Comegys 
may  be  required,— namely,  cold  affusions  while  the  child  is  sitting  in  a 
cold  bath.  The  effect  is  usually  immediate,  quiet  and  sleep  at  once 
replacing  the  wakeful  restlessness  so  distressing  to  mother  and  child. 
There  may  be  a  few  instances  of  sudden  collapse  with  low  temperature 
from  exhaustion  by  the  serous  discharges,  but  usually  cases  in  which  the 
disease  is  said  to  "go  to  the  head' '  are  those  in  which  the  temperature 
rises  so  high  as  to  produce  brain-symptoms  ;  under  these  circumstances 
the  vigorous  use  of  external  cold  is  imperatively  demanded. 

The  high  temperature  that  prevails  in  sthenic  pneumonia  would  appear 
urgently  to  demand  the  abstraction  of  heat,  and,  although  the  prejudices  of 
the  profession  and  the  laity  were  in  the  beginning  strongly  opposed  to  the 
use  of  the  cold  bath  in  pulmonary  inflammation,  gradually  the  method  has 
come  into  practice.  Liebermeister,  in  one  of  his  early  publications,  stated 
that  whilst  in  six  hundred  and  ninety-two  cases  of  pneumonia  treated  in 
the  hospital  of  Basel  in  various  ways  the  mortality  was  25.3  per  cent.,  in 
two  hundred  and  thirty  cases  treated  in  the  same  hospital  by  the  thorough 
antipyretic  method  the  mortality  was  only  16.5  per  cent.,  and  there  can 
be  no  doubt  that  in  properly  selected  cases  bathing  does  great  good. 

It  must,  however,  be  remembered  that  a  moder  ite  pyrexia  does  not 
do  great  harm  to  the  system  unless  it  continues  for  a  length  of  time,  and 
hence  in  those  diseases  which,  like  pneumonia,  last  but  a  few  days  the 
reduction  of  temperature  is  not  so  important  as  in  affections  in  which  the 
fever  is  of  long  continuance.  Thus,  a  temperature  of  103°  F.  may  be 
disregarded  in  a  short  pyrexia,  whereas  in  a  typhoid  fever  it  would  call 
imperatively  for  the  use  of  external  cold.  Further,  in  acute  internal  in- 
flammations the  temperature  can  very  frequently  be  reduced  with  ad- 


38  CALORIC. 

vantage  by  the  local  application  of  cold  ;  thus,  in  pneumonia  cold  com- 
presses to  the  chest  may  be  employed  ;  in  dysentery  the  free  use  of  ice 
suppositories  and  of  large  injections  of  ice-cold  water  is  often  of  the 
greatest  service,  both  by  the  local  and  general  influence. 

It  being  acknowledged  that  in  cases  with  long- continued  pyrexia  the 
external  use  of  cold  is  a  much  safer  and  more  efficient  means  of  reducing 
the  temperature  than  are  antipyretic  drugs,  the  practical  question  presents 
itself  as  to  what  are  the  centra-indications  to  the  use  of  cold  in  typhoid 
and  other  allied  fevers. 

According  to  ideas  formerly  held,  bronchitis  and  pneumonia  would 
especially  seem  to  be  in  the  way.  The  serious  lung  affections  of. low 
fevers  are,  however,  chiefly  dependent  upon  the  general  adynamia, 
which  is  in  turn  largely  the  result  of  the  excessive  temperature  ;  and  we 
have  no  doubt  of  the  correctness  of  the  assertion  made  by  Liebermeister, 
that  in  the  exanthematous  fevers  "  pneumonia,  hypostatic  congestion,  and 
the  like  offer  no  reason  for  suspending  the  baths  ;  the  hypostatic  troubles 
sometimes  disappear  under  their  use."  If  in  the  beginning  of  a  typhoid 
fever  a  severe  bronchitis  or  pneumonia  arise  without  great  elevation  of 
temperature,  some  hesitation  may  properly  be  felt  in  producing  active 
antipyresis  with  cold.  If,  however,  the  symptoms  occur  late  in  the  fever 
they  do  not  centra-indicate  the  use  of  the  bath  ;  and  even  early  in  the 
fever,  if  the  pyrexia  be  severe,  balneal  measures  should  be  practised. 

Liebermeister  affirms  that  perforation  of  or  hemorrhage  from,  the 
bowels  is  a  contra- indication  to  the  use  of  cold  in  typhoid  fever,  because 
cold  has  a  tendency  to  produce  determination  of  blood  to  the  internal 
organs.  The  experience  of  Wunderlich14  is,  however,  very  much  op- 
posed to  this  idea  of  Liebermeister' s.  He  treated  sixteen  typhoid  cases 
of  severe  intestinal  hemorrhage  with  cold  baths,  with  but  two  deaths, 
neither  of  which  resulted  directly  from  the  hemorrhage,  one  being  from 
intestinal  perforation  and  one  from  severe  pneumonia.  This  mortality  is 
certainly  a  very  small  one,  for  when  cold  water  was  not  employed,  out  of 
thirty-two  cases  Griesinger  had  ten  deaths  ;  out  of  twenty-one,  Jenner  lost 
seven  ;  out  of  fourteen,  Gietl  lost  six  ;  and  Jaccoud15  had  six  deaths  in  six 
cases.  Bauer,16  however,  is  in  agreement  with  Liebermeister  in  believing 
that  the  baths  should  be  discontinued  during  intestinal  hemorrhage.  Yet 
their  views  seem  to  be  based  upon  preconceived  theory  rather  than  upon 
actual  trial.  The  proportion  of  cases  in  which  intestinal  hemorrhage  occurs 
does  not  seem  to  be  increased  by  the  cold-water  treatment ;  at  least  Gols- 
dammer17  states  that  under  the  older  methods  thirteen  thousand  five  hun- 
dred and  sixty-three  cases  gave  five  hundred  and  thirty  of  intestinal  hem- 
orrhage, while  five  thousand  six  hundred  and  thirty -six  cases  of  cold-water 
treatment  yielded  two  hundred  and  forty  of  intestinal  hemorrhage,  the 
percentage  being  in  the  two  cases  respectively  3.9  and  4. 2.  Menstruation 
is  not  a  centra-indication.  Brandt  appears  to  consider  any  contra-indica- 
tion  to  the  use  of  the  cold  bath  in  typhus  fever  a  myth,  and  the  drift  of 
the  testimony  is  such  that  no  local  internal  disease  except  feeble  heart 


COLD    IN    PYREXIA.  39 

ought  to  be  considered  as  absolutely  contra-indicating  the  use  of  cold 
baths  when  the  temperature  is  high  in  typhus  or  typhoid  fever. 

It  is  otherwise  when  there  is  a  general  tendency  to  collapse, — when  the 
heart  is  so  weak  that  local  stases  of  blood  occur  in  almost  all  the  internal 
organs.  Under  these  circumstances  the  circulation  has  not  sufficient 
power  thoroughly  to  equalize  animal  heat,  so  that  it  is  possible  to  cool  the 
exterior  of  the  body  several  degrees  without  materially  affecting  the  tem- 
perature of  the  interior. 

Moreover,  the  first  effect  of  cold  water  upon  the  surface  of  the  body  is 
to  drive  blood  into  the  interior,  and  if  the  heart  be  excessively  feeble  there 
is  grave  danger  of  severe  internal  congestion,  and  even  of  paralysis  of  a 
feeble  right  heart.  The  great  contra- indication  to  the  use  of  external  cold 
is,  therefore,  profound  adynamia  or  excessive  heart  weakness.  Whenever 
there  is  any  doubt  in  the  practitioner's  mind  upon  this  score  in  an  indi- 
vidual case,  the  attempt  should  be  made  to  reduce  the  temperature  within 
bounds  by  immersion  in  tepid  water. 

In  carrying  out  the  antipyretic  treatment  of  fever  certain  general  con- 
siderations should  never  be  forgotten.  So  long  as  the  temperature  of  the 
body  remains  distinctly  above  the  normal  there  is  no  danger  of  any  patient 
taking  cold.  The  fall  of  the  bodily  temperature  may  continue  after  the 
removal  of  the  patient  from  the  bath  ;  hence  it  is  important  that  the  pa- 
tient be  taken  out  of  the  bath  so  soon  as  the  temperature  reaches  100.5° 
F.  The  temperature  at  which  the  bathing  should  be  commenced  varies 
with  the  probable  length  of  the  pyrexia  ;  in  typhoid  fever  we  would  put  the 
limit  at  102.5°  F-  *n  tne  mouth.  As  it  is  possible  to  cool  the  axilla  with- 
out cooling  the  interior  of  the  body,  all  temperatures  should  be  taken  in 
the  mouth  or  the  rectum.  The  object  of  the  bath  is  a  reduction  of  the 
temperature,  and  unless  this  is  effected  no  good  results.  On  the  other 
hand,  it  is  always  of  importance  to  avoid,  as  far  as  may  be,  shock,  dis- 
comfort, or  the  possibility  of  overdoing  the  heat-reduction  ;  hence  the 
rule  in  the  choice  of  the  methods  of  cooling  the  body  to  employ  that 
which  will  accomplish  the  desired  effect  with  the  least  disturbance. 

Rarely  in  the  adult,  more  frequently  in  the  child,  free  sponging  of  the 
exposed  body  with  cold  water  and  alcohol  will  suffice.  Next  in  power 
comes  the  cold  pack,  in  which  the  naked  patient  is  wrapped  in  a  sheet 
dripping  with  ice- water,  left  uncovered  save  by  the  sheet,  and  sponged 
with  cold  water  from  time  to  time.  Next  is  the  tepid  bath,  90°  F. ;  then 
the  tepid  bath  cooled,  whilst  the  patient  is  in  it,  by  the  addition  of  cold 
water  or  of  pieces  of  ice.  Some  prefer  to  put  the  patient  directly  into 
water  of  75°  F.,  but  the  gradual  cooling  of  the  bath  seems  to  us  preferable. 
When  a  portable  bath-tub  can  be  brought  to  the  bedside  of  the  patient 
and  readily  filled  and  emptied,  its  use  is  accompanied  by  less  fatigue 
and  disturbance  than  are  any  other  efficient  means  of  employing  cold. 
The  patient,  wrapped  in  a  sheet,  is  to  be  lifted  into  the  bath  by  two 
attendants,  and  then  made  comfortable  with  pillows,  etc.  Unless  the 
pyrexia  be  very  severe,  the  bath  should  be  at  a  temperature  of  90°  F.  and 


40  CALORIC 

cooled  down  pro  re  nata.  When  no  portable  bath-tub  is  at  hand,  efficient 
antipyresis  may  be  had  by  lifting  the  patient,  wrapped  in  a  sheet,  upon  a 
cot  covered  with  a  rubber  blanket,  and  sousing  rather  than  sponging  him 
with  cold  water  from  a  large  carriage-sponge.  If  the  sacking-bottom  or 
the  canvas  of  the  cot  be  so  loose  as  to  sag  down  several  inches,  and  the 
rubber  blanket  be  turned  up  at  the  bottom  and  top  over  a  wide  board 
nailed  across  the  top  and  bottom,  the  patient  during  the  sponging  lies  in 
a  big  pool  of  water,  and  all  the  effect  of  the  cold  bath  is  obtained  by 
removing  with  a  carriage-sponge  this  water  as  fast  as  heated,  and  sousing 
fresh  cold  water  (ice-water,  if  necessary)  freely  over  the  upper  part  of  the 
patient.  Sometimes  the  bed  in  which  the  patient  lies  can  be  arranged 
with  a  rubber  sheet  drawn  up  over  the  pillow  and  down  over  the  foot, 
folded  into  a  trough,  and  the  cold  water  applied  without  wetting  the  bed. 

During  the  bath  the  hands  should  be  kept  out  of  the  water,  and  the 
surface  of  the  body  should  be  briskly  rubbed  so  as  to  divert  the  attention 
of  the  patient,  and  also  to  prevent  as  far  as  may  be  the  driving  of  the  blood 
from  the  surface  of  the  body  by  the  local  effects  of  the  cold.  When  the 
circulation  is  weak,  advantage  is  often  gained  by  putting  the  feet  or  even 
both  feet  and  hands  upon  a  hot-water  bag. 

The  temperature  of  a  fever  patient  should  during  the  treatment  be 
taken  every  three  or  four  hours.  Theoretically  the  bath  should  be  re- 
peated whenever  the  temperature  gets  above  the  limit,  102.5°  F. ,  but 
practically  it  is  best  not  to  use  the  bath  oftener  than  once  every  three  or 
four  hours.  It  should  be  administered  if  required  during  the  night  as 
well  as  during  the  day,  and  its  use  should  not  be  allowed  to  interfere  with 
any  other  treatment  which  may  be  indicated. 

In  explaining  the  use  of  the  method  to  the  patient  or  friends,  it  must 
not  be  forgotten  that  the  cold  bath  in  typhoid  fever  and  other  acute  dis- 
eases associated  with  high  pyrexia  does  not  arrest  the  disease-processes  ; 
and,  whilst  it  may  greatly  lessen  the  mortality,  it  shortens  the  duration  of 
the  disease  only  in  so  far  as  it  prevents  complications.  On  the  other 
hand,  the  disease-processes  do  not  exhaust  the  patient  so  much  as  when 
the  fever  is  allowed  to  continue  unchecked,  so  that  convalescence  is  usually 
much  more  rapid  than  under  the  older  plan  of  treatment.  By  the  anti- 
pyretic treatment  the  intense  prostration,  delirium,  stupor,  carphologia, 
involuntary  passages,  and  other  manifestations  of  the  typhoid  state  are 
greatly  lessened. 

REFERENCES. 

1.  MOSLER      ....  V.  A.  P.  A.,  Ivii.  9.  ROEHRIG  and  ZUNTZ  .  A.  G.  P.,  iv.  66. 

2.  LlEBERMEISTEK   .  D.  A.  K.  M.,  1.  IO.    SASSETZKY  .      .     .  V.  A.  P.  A.,  XC1V.  517. 

3.  WEISFLOG  .   .   .   .  D.  A.  K.  M.,  ii.  570.  n.  BAUER  and  KUNSTLE  .  D.  A.  K.  M.,  xxiv. 

4.  KERNIG      .       .   .  A.  A.  and  P.,  1860.  12.  SCHLEICH    .    .   .  A.  E.  P.  P.,  1875. 

5.  LIEBERMEISTER  .  Beobacht.     und     Versuche        13.  COMEGVS  .   .   .   .  P.  M.  T.,  v.  665;  A.  J.  M. 

iiber  die  Anwendung  des  S.,  Oct.  1876. 

kalten      Wassers,     etc.,  14.  WUNDERLICH  .  S.  Jb.,  clvi.  101. 

Leipzig,  1868.  15.  JACCOUD    .   .   .  .  Path.  Intern.,  ii.  758. 

6.  GILDEMEISTER    .  V.  A.  P.  A.,  Hi.  131.  16.  BAUER    ...  .  S.  Jb.,  clvi.  101. 

7.  LEHMANN  .   .  .  .  V.  A.  P.  A.,  1873.  Iviii.  17.  GOLSDAMMER  .  B.  K.  W.,  1877,  98. 

8.  LIEBERMEISTER  .  D.  A.  K.  M.,  x.  89,  425. 


CHAPTER    IV. 


FIG.  i. 

7\ 


c 

1           \ 

I 

^ 

\ 

z 

ELECTRICITY. 

GENERAL  CONSIDERATIONS. — Electricity  is  a  force  which  is  developed 
in  various  ways,  but  which  is  essentially  the  same  entity  under  all  circum- 
stances. When  it  is  obtained  by  rubbing  two  surfaces 
together,  it  is  known  as  frictional  electricity  ;  when  it 
is  obtained  by  the  union  of  two  dissimilar  metals,  it  is 
called  galvanism.  Frictional  electricity  is  almost  never 
used  in  medical  practice,  and  we  shall  say  nothing  more 
about  it  in  this  book. 

There  are  a  large  number  of  different  patterns  or 
arrangements  of  the  elements  which  generate  gal- 
vanism, but  the  ideal  or  typical  cell  may  be  said  to  be 
formed  of  two  dissimilar  metals  immersed  in  some  cor- 
rosive liquid  and  connected  with  each  other  by  a  piece 
of  wire  externally.  Under  these  circumstances  the 
current  starts  from  the  metal  most  easily  corroded, 
passing  through  the  liquid  to  that  less  easily  acted 
upon,  and  from  this  over  the  external  wire  to  the 
starting-point.  The  external  end  of  the  least  easily  corroded  plate  is 
therefore  always  giving  off  electricity,  and  is  known  as  the  -f  or  positive 
pole,  while  the  corresponding  end  of  the  other  plate  is  constantly  re- 
ceiving electricity,  and  is  spoken  of  as  the  —  or  negative  pole.  When 
wires  are  attached  to  these  plates  they  become,  as  it  were,  prolongations 
of  the  plates,  and  their  ends  constitute  the  poles.  Thus,  in  the  diagram, 
C=  copper,  Z=  zinc,  P  and  N=-  poles,  and  the  arrows  show  the  direc- 
tion of  the  current.  The  positive  pole  is  called  the  anode  (<*vcE,  upward, 
and  <J<Wp,  a  way)  ;  the  negative,  the  cathode  (xara,  downward,  and  <J<W?). 

As  the  electric  current  does  not  primarily  exist,  it  is  evident  that  in  the 
typical  or  ideal  galvanic  cell  there  must  be  something  which  sets  it  in 
motion.  This  force  is  the  so-called  electro-motor  force,  and  has  been 
determined  by  physicists  to  be  a  definite  quantity  for  the  same  combina- 
tion of  metals  at  the  one  temperature.  This  force  is  generated  at  the 
point  of  contact  of  the  metals,  in  obedience  to  the  law  discovered  by 
Volta,  that  when  two  metals  are  in  contact  with  each  other  a  disturbance 
of  the  electrical  conditions  of  those  metals  occurs.  The  amount  and 
energy  of  this  disturbance  vary  according  to  the  nature  of  the  metals,  and 
experiments  have  shown  that  all  metals  have  definite  electro-motor  powers 
or  properties,  and  that  they  can  readily  be  arranged  in  a  regular  series. 

41 


42  ELECTRICITY. 

A  study  of  this  series  is  not  necessary  to  an  understanding  of  electro- 
therapeutics, and  the  reader  desirous  of  knowledge  upon  this  especial 
point  is  referred  to  works  on  physics.  It  must  be  borne  in  mind  that  the 
electro-motor  force  is  constant,  so  that  in  any  given  combination  of  metals 
in  a  galvanic  cell  the  electro-motor  force  is  always  the  same,  whether  the 
plates  of  the  metal  be  large  or  small,  whether  the  solution  be  an  acid,  a 
saline,  or  pure  water.  The  strength  of  the  current  is  not,  however, 
decided  entirely  by  the  electro-motor  force  of  the  cell.  Every  known 
substance  refuses  more  or  less  imperiously  to  allow  the  passage  of  elec- 
tricity. The  best  conductors  oppose  a  really  very  great  resistance.  Now, 
it  is  evident  that  this  resistance  is  opposed  to  the  electro-motor  force,  and 
that  if  it  be  greater  than  the  latter  it  will  altogether  prevent  the  passage 
of  any  current.  The  strength  of  the  current,  then,  depends  upon  the 
relation  between  the  resistance  and  the  electro-motor  force  ;  and  we  have 
the  celebrated  law  of  Ohm,  which  may  be  expressed  by  the  formula 

e  (electro-motor  force}         ,.    , 
c  {current-strength)  =  - — "r .      I  his  law  experiment  has 

shown  to  be  imperative,  no  increase  or  diminution  of  the  size  of  the 
plates,  no  change  in  the  character  of  the  solution,  affecting  it. 

The  resistance  to  the  current  in  a  galvanic  combination  is  a  double 
one  :  inside  of  the  cell  the  fluid  between  the  plates  opposes  the  passage 
of  the  electricity,  and  outside  of  the  cell  the  conductor  which  completes 
the  circuit  also  offers  a  resistance.  The  reason  a  battery  almost  ceases 
to  yield  a  current  when  water  is  substituted  for  the  acid  usually  employed 
is  not  a  purely  chemical  one,  but  simply  because  water  is  an  almost  com- 
plete non-conductor,  and  offers  triumphant  resistance  to  the  current,  while 
the  acid  conducts  and  readily  allows  the  current  to  pass.  The  entire  re- 
sistance (r~)  is  then  made  up  of  two  factors  :  the  internal  resistance  (ir), 
and  the  external  resistance  (er).  The  formula  of  Ohm  may  therefore  be 

read  c=—       — . 
ir  +  er 

As  already  stated,  when  the  plates  of  a  cell  are  increased  in  size  the 
electro-motor  force  is  not  increased,  but  as  the  surfaces  of  the  plates  are 
increased  the  diameter  of  the  conductor — i.e.,  the  transverse  section  of 
the  fluids  between  the  plates — is  increased  ;  and  consequently,  as  the 
resistance  in  a  conductor  is  inversely  as  the  size  of  its  cross-section,  the 
strength  of  the  current  is  increased.  To  make  this  a  little  clearer,  sup- 

g 

pose  ir  in  a  certain  cell  equal  10,  then  c  =  —          -  ;  if  now  the  plates  of 

10  +  er 

e  e 

the  cell  be  doubled  in  size,  c  =  r^—     -  =  —       — .A  similar  result — i.e., 

Y  +  er       5  +  er 

lessening  of  the  internal  resistance — can  be  achieved  by  shortening  the 
distance  between  the  plates  of  the  cell, — i.e.,  the  length  of  the  conductor, 
— or  by  in  any  way  making  the  intervening  liquid  a  better  conductor. 

The  change  in  strength  of  a  current  by  the  increase  of  the  size  of 
the  plates  of  the  cells  can  readily  be  expressed  by  the  formula  of  Ohm. 


ELECTRICITY.  43 

If  the  letters  signify  as  before,  and  the  internal  resistance  be  diminished 

g 
y  times  by  increasing  the  size  of  the  plate  y  times,  instead  of  c  —  - — — — 

e  If,  instead  of  a  single  cell,  a  number  of  cells  are  ar- 

~~  ir        ~~ '     ranged  in  such  a  way  that  the  copper  of  one  is  con- 

y  nected  with  the  zinc  of  the  next,  the  electro-motor  force 

of  the  combination  is  equal  to  the  sum  of  the  electro-motor  force  of  all  the 

cells  :  thus,  if  e  =  the  electro-motor  force  of  the  single  cell,  and^  =  the 

number  of  cells,  the  electro-motor  force  of  the  battery  will  be  ye.     It  is 

plain  that  the  internal  resistance  of  the  battery  is  also  increased  y  times, 

ye 

so  that  the  formula  of  Ohm  will  stand  c  =    .     , . 

ytr  +  er 

Of  course  the  strength  of  a  current  is  greatly  affected  by  the  external 
resistance.  In  very  many  instances  the  external  resistance  is  enormous. 
Suppose,  then,  that  this  external  resistance  in  a  given  case  be  1000  times  the 

g 

internal  resistance,  the  formula  of  Ohm  will  read,  c  =-. —  — r .     It  is 

ir  +  1000  ir 

evident  that  under  these  circumstances  ir,  the  internal  resistance,  becomes 
very  insignificant,  and  that  very  little  is  gained  by  increasing  the  size  of 
the  plates, — i.e. ,  by  diminishing  the  internal  resistance  ;  for  if  the  plates 
were  increased  fivefold,  the  increase  of  the  strength  of  the  current  would 

e  e 

only  be  the  difference  between  -  —  and  -  — — ,  a  differ- 

ir  .  ir  +  looo  ir 

—  -f  1000  ir 

o 

ence  which  is  very  slight.  On  the  other  hand,  when  the  external  re- 
sistance is  very  great,  everything  is  gained  by  increasing  the  number  of 

c   g 

cells, — i.e.,  increasing  the  electro- motor  power  ;  for  -  —  gives  a 

5  ir  -f  icoo  ir  & 
g 

very  different  result  from  -  -r.     When,  therefore,  the  external 

tr  -f-  looo  tr 

resistance  is  many  times  greater  than  the  internal,  practically  nothing  is 
gained  by  increasing  the  size  of  the  plates,  everything  by  increasing  the 
number  of  the  elements. 

The  converse  of  the  above  reasoning  also  holds.  If  the  external 
resistance  be  very  slight,  the  internal  rises  in  importance.  Thus,  sup- 

ir  e 

pose  er  •=. .     Then  the  formula  would  be  c  = : — .     In  this 

looo  .  ir 

tr  4-  • — 
1000 

case  a  great  deal  is  gained  by  increasing  the  size  of  the  plates,  for 

e  e 

-. —     — —  gives  a  very  different  result  from  -  — .     In  such  a  case, 

ir         ir    '  .  ir 

tr  -\-  — 
5       icoo  looo 

by  quintupling  the  size  of  the  plates  the  strength  of  the  current  is  prac- 
tically increased  fivefold.  On  the  other  hand,  it  is  plain  that  when  the 
external  resistance  is  slight  the  gain  by  increasing  the  number  of  cells 
is  a  slight  one,  for  the  internal  resistance  is  increased  as  many  times 


44  ELECTRICITY. 

as  the  electro-motor  force.     Thus,  if  five  cells  are  used,  the  formula  will 

be  c  =  -  — : — -,  which  will,  of  course,   give  practically  the   same 

S  ir  + 

1000 

e 

result  as  — ; — . 

ir 

n-  4- 

1000 

The  law,  then,  may  be  stated  to  be  that  when  the  external  resistance 
is  very  slight,  increasing  the  number  of  the  elements  has  no  practical 
effect  upon  the  strength  of  the  current,  while  an  increase  of  the  size  of  the 
elements  has  the  greatest  effect. 

When  there  is  no  very  great  disproportion  between  the  internal  and 
the  external  resistance,  it  is  evident  that  the  strength  of  the  current  may 
be  increased  by  increasing  either  the  size  or  the  number  of  the  elements. 

e  e 

Thus,  if  er  =  ir.  c  =  -. — -  -  =  -. — - — ,-  ;  and  increasing  the  size  of  the 
tr  4-  er        ir  -f  tr 

plates  fourfold  will  give  the  formula  c  =  - — :     -  ;  or  increasing  the  num- 

-  4-  ir 
4 

ber  of  the  elements  to  four  will  yield  the  formula  c  —  -  — .     Perhaps 

4  tr  4-  tr 

the  result  will  be  clearer  if  figures  be  used.     Suppose  e  =  100,  ir  =  10, 

100 

and  cr  =  10.      Then  the  first  formula  will  be  c  =  -  -  =  5  ;    the 

10  4-  10 

T  OO  1  OO 

second,  c—-  -  •=•  8  :  the  third,  c  =  -  =8.     When,  there- 

10  40  4-  10 

-4-IQ 

4 

fore,  the  external  and  the  internal  resistance  are  equally  balanced,  the 
strength  of  the  current  is  equally  increased  by  increasing  either  the  num- 
ber or  the  size  of  the  plates. 

The  application  of  the  foregoing  principles  to  electro-therapeutics  is  a 
very  simple  one.  In  the  ordinary  applications  of  electricity  to  the  body 
the  resistance  of  the  tissues  is  very  many  times  greater  than  the  internal 
resistance  of  any  battery,  and  consequently  the  latter  may  be  totally  dis- 
regarded. Hence  for  ordinary  purposes  the  formula  stands  c  =  —,  and 

power  can  be  gained  only  by  increasing  e, — that  is,  by  augmenting  the 
number  of  cells. 

When,  however,  it  is  desired  to  act  upon  the  blood  in  an  aneurismal 
sac,  the  needles  are  brought  close  to  each  other  ;  and,  moreover,  the 
blood  is  a  comparatively  good  conductor  of  electricity.  Hence  in  such 
cases  the  external  resistance  is  so  much  reduced  that  the  internal  becomes 
of  such  importance  that  it  should  not  be  overlooked.  It  follows,  there- 
fore, that  when  an  aneurism  is  to  be  acted  upon  the  plates  should  be 
increased  in  size,  while  at  the  same  time  a  number  of  cells  should  be 
used. 


ELECTRICITY.  45 

In  the  so-called  ' '  galvano-cautery' '  the  current  is  not  passed  through 
the  body  at  all,  but  through  a  wire,  which  is  thus  kept  at  a  white  heat. 
In  this  case  the  external  resistance  is  vastly  less  than  when  human  tissues 
form  a  part  of  the  circuit.  Hence  it  becomes  a  matter  of  importance  to 
reduce  to  as  great  a  degree  as  possible  the  internal  resistance,  and  the 
elements  or  plates  should  be  very  large  and  should  be  placed  very  close 
to  one  another  in  the  cells.  The  external  resistance  is  not,  however, 
so  slight  that  it  can  be  entirely  overlooked,  and  hence  a  number  of  cells 
are  combined  with  one  another,  so  as  to  give  sufficient  electro-motor 
force. 

In  writing  or  speaking  about  the  use  of  electricity  in  medicine,  it  is  a 
matter  of  great  importance  to  avoid  the  use  of  the  old  terms  quantity  and 
intensity,  which,  to  use  the  language  of  an  eminent  writer  on  galvanism, 
"are  remnants  of  an  erroneous  theory."  The  amount  of  mystification 
which  has  been  produced  by  talk  concerning  the  therapeutic  effects  of 
•currents  of  large  quantity  with  low  intensity  as  contrasted  with  those  of 
currents  of  high  intensity  and  small  quantity  is  equalled  only  by  the 
amount  of  nonsense  which  has  been  written.  Currents  of  galvanism 
have  really  only  one  attribute, — i.e.,  current-strength, — and  that  is  in 
strict  accordance  with  the  law  of  Ohm. 
g 

If  £— -  it  is  evident  that,  in  order  to  have  a  unit  by  which  there  can 
r 

be  a  measurement  of  an  electric  current,  it  is  necessary  to  have  a  unit  of 
resistance  and  a  unit  of  electro-motor  force.  The  unit  which  has  been 
finally  settled  upon  by  electricians  as  the  measure  of  electro-motor  force 
is  known  as  a  volt.  It  is  equivalent  to  io8  (10  raised  to  its  eighth  power) 
absolute  French  units  of  force.*  The  unit  of  resistance  is  termed  an  ohm, 
and  equals  io9  absolute  French  units.  Substituting  these  units  for  their 

representative  letters  in  the  formula  c—    ,  we  get  c  =  In  this  way 

r  i  ohm 

the  unit  of  current-strength  is  obtained,  and  is  known  as  an  ampere.  This 
unit  is,  however,  entirely  too  large  for  practical  purposes.  It  is  therefore 
generally  substituted  by  the  so-called  milliampere,  which  is  the  one- 
thousandth  part  of  an  ampere,  or  —  The  term  galvanometer 

looo   ohms 

has  long  been  used  in  electricity  as  the  name  of  an  instrument  which 
shows  the  existence  of  an  electro-current.  An  absolute  galvanometer  is 
one  which  reveals  not  only  the  current,  but  also  the  amount  of  electricity 
that  is  passing.  As  good  absolute  galvanometers  are  now  manufactured 
which  measure  the  current  in  milliamperes,  it  would  seem  at  first  to  be 


*  All  forces  are  convertible  into  one  another,  and  hence  it  is  possible  to  refer  the  unit 
which  is  employed  in  measuring  electricity,  heat,  or  other  force  to  what  is  known  as  the 
absolute  unit  of  force.  The  absolute  unit  of  force  is  always  mechanical,  and  has  in  the 
past  varied  in  different  countries.  At  present,  however,  scientists  almost  universally 
adopt  the  French  unit,  which  is  a  representation  of  the  amount  of  force  required  to  raise 
•one  gramme  through  one  centimetre  of  distance  in  one  second. 


46  ELECTRICITY. 

a  very  easy  matter,  in  testing  the  excitability  of  nerves  or  in  reporting 
cases  treated  by  electricity,  to  state  exactly  how  many  milliamperes  passed 
through  the  nerve  or  through  the  system  ;  in  other  words,  it  would  seem 
easy  to  have  a  dosage  of  electricity  comparable  to  that  of  medicines. 
Unfortunately,  the  affair  is  not  so  simple,  chiefly  on  account  of  the  dif- 
fusion of  the  electrical  current  which  naturally  takes  place  during  its  pas- 
sage through  the  human  body.  If,  for  instance,  an  electrode  of  a  square 
inch  of  surface  be  used,  the  effect  upon  the  organism  must  be  different 
from  that  which  would  be  obtained  by  employing  an  electrode  of  twenty 
square  inches.  In  the  one  case  a  concentrated  current  would  pass  at  least 
for  some  little  distance  into  the  body,  in  the  other  a  large  number  of  pro- 
portionally feebler  currents  would  enter  from  the  beginning.  More  than 
this,  when  it  is  intended  to  galvanize  a  fixed  spot,  as  a  ganglion  or  nerve- 
trunk,  it  is  rarely  possible  to  note  exactly  what  portion  of  the  current 
which  enters  the  body  reaches  the  desired  spot  and  how  much  of  it  is 
diffused  through  other  tissues.  (See  paragraph  on  conduction.)  In 
order,  therefore,  to  compare  results  obtained  by  different  electricians,  or 
by  the  same  electrician  upon  the  same  case  in  successive  days,  or  in  dif- 
ferent cases,  it  is  essential  to  know  exactly  the  size  of  the  electrodes  and 
the  positions  at  which  they  were  placed  upon  the  body.  To  facilitate 
measurements,  Mr.  C.  W.  Miiller  has  proposed  that  in  therapeutic  elec- 
tricity a  fraction  be  used  to  express  the  concentration  of  the  current  which 
is  employed,  the  numerator  of  the  fraction  to  consist  of  the  number  of 
milliamperes,  the  denominator  of  the  number  of  square  centimetres  in  the 
electrode.  Thus,  the  fraction  -^  would  mean  that  a  current  of  one  mil- 
liampere  strength  had  been  employed  with  an  electrode  of  thirty  centi- 
metres of  surface,  while  the  fraction  ^  would  mean  that  the  current  of 
four  milliamperes  had  been  employed  through  an  electrode  of  sixteen 
square  centimetres  of  surface.  These  fractions  do  not  express  in  any  way 
the  relative  positions  of  the  electrode,  and  the  alteration  of  half  an  inch 
in  the  position  of  an  electrode  on  the  surface  of  the  body  may  double  or 
halve  the  amount  of  a  current  which  reaches  the  desired  spot.  Practical 
dosage  of  electricity  in  therapeutics  is  probably  a  chimera,  and  certainly 
has  not  yet  been  satisfactorily  achieved.  It  is  possible  that  in  certain 
delicate  cases,  with  very  careful  investigators,  the  measurement  may  be 
employed  with  advantage  for  the  study  of  physiological  results.  But  one 
who  is  familiar  with  the  average  training  in  physical  science  of  physicians 
who  use  electricity  must  recognize  that  the  publications  of  electrical 
measurements  amount  to  little  more  than  a  show  of  scientific  accuracy. 

For  ordinary  use  in  diagnosis  and  treatment  of  disease  galvanometers 
are  not  required,  the  experienced  medical  electrician  being  sufficiently 
guided  by  the  sensations  of  the  patient  and  the  muscular  effects  achieved. 

A  dense  fog  has  been  thrown  around  the  subject  of  electro-therapeutics 
by  the  idea  that  there  are  various  essentially  different  forms  of  electricity. 
The  current  which  flows  from  a  cell  or  a  combination  of  cells  is  spoken  of 
as  a  continuous  current,  or  sometimes  as  a  primary  current ;  besides  this, 


ELECTRICITY.  47 

modern  therapeutists  use  another  series  of  currents,  which  are  known  as 
induced  currents. 

The  term  primary  current  is  often  applied  to  one  of  these  induced 
currents.  If  we  employ  the  name  continuous  current  for  that  current 
derived  from  the  galvanic  cell,  we  must  continually  be  speaking  of  the 
interrupted  continuous  current,  which  certainly  is  inelegant.  We  shall, 
therefore,  employ  the  name  chemical  current  or  galvanic  current  to  desig- 
nate that  form  of  electricity  which  is  generated  in  the  galvanic  cell. 

If  a  coil  of  insulated  wire  have  a  bar  of  soft  iron  placed  in  its  centre 
and  be  surrounded  by  an  external  coil  of  wire,  when  a  chemical  current  is 
passed  through  the  first  coil,  owing  to  physical  laws  which  it  is  not  neces- 
sary here  to  consider,  every  time  the  galvanic  circuit  is  completed  or  inter- 
rupted a  brief  current  of  electricity  is  induced  in  the  inner  or  first  coil,  and 
also  a  similar  current  in  the  outer  or  second  coil.  The  only  physical  facts 
which  it  is  necessary  for  us  to  know  are  that  these  induced  currents  are 
very  brief  and  of  great  strength,  also  that  they  are  to-and-fro  currents, — 
that  is,  run  in  opposite  directions  in  each  individual  coil.  Thus,  in  the 
inner  or  first  coil,  when  the  galvanic  circuit  is  closed,  the  induced  current 
in  the  inner  coil  runs  parallel  to  the  generating  chemical  current ;  but 
when  this  latter  current  is  broken,  the  induced  current  runs  in  a  contrary 
direction.  In  the  outer  coil,  the  induced  current,  which  is  instantaneously 
developed  when  the  galvanic  current  is  sent  through  the  inner  coil,  pursues 
a  direction  opposite  to  that  of  the  chemical  current ;  but  when  the  latter 
is  broken,  the  return  induced  current  in  the  outer  coil  runs  parallel  to  the 
generator  current. 

As  these  induced  currents  run  backward  and  forward,  to  and  fro,  in 
this  way,  it  would  appear  that  there  could  not  be  any  negative  or  positive 
pole  to  the  battery  which  generates  them,  for  if  one  end  or  pole  of  the 
wire  constituting  the  coil  be  negative  in  regard  to  the  first  induced  current, 
it  must  be  positive  in  regard  to  the  second  or  return  current.  This  is 
assuredly  true  so  far  as  concerns  the  outer  or  second  coil,  but  is  not  true 
for  the  inner  or  first  coil,  as  is  readily  understood  by  means  of  the  diagram 
of  an  induction  battery  given  on  page  48. 

It  is  plain  that  when  the  current  is  passing,  the  hammer  h  being  in  the 
position  represented  in  the  diagram,  m  will  become  magnetic  and  attract  h. 
This  at  once  breaks  the  current,  and  an  induced  current  runs  through  the 
first  coil  and  is  received  by  the  patient  grasping  the  handles  P  P.  The 
instant  the  current  is  interrupted,  m  loses  its  magnetism  and  the  spring- 
hammer  flies  back.  Now  the  circuit  is  closed,  and  for  the  second  time  an 
induced  current  runs  through  the  first  coil,  c.  It  is  evident,  however,  that 
this  induced  current  of  closure  will  not  pass  through  the  body  of  the  per- 
son grasping  the  handles  P  P,  but  will  pass  along  h  through  the  cell  to 
the  other  end  of  the  coil,  as  a  shorter  route  and  one  of  vastly  less  resist- 
ance. It  is  plain  that  from  the  inner  or  first  coil  the  induced  current  of 
broken  circuit  alone  passes  through  the  body  of  the  patient. 

In  regard  to  the  outer  coil,  it  is  evident  that  when  the  circuit  is  closed 


48 


ELECTRICITY. 


the  momentary  induced  current  must  run  through  the  body  of  whoever 
grasps  the  handles  P'  and  /*,  and  that  the  return  current  which  passes 
when  the  circuit  is  broken  must  take  the  same  route. 

It  follows  from  the  above  considerations  that  the  current  of  the  first 
foil  runs  through  the  patient  in  one  direction  only,  and  electricians  may 

FIG.  2. 


G,  galvanic  element,  with  the  +  and  —  metals  in  it ;  c,  coil  in  which  the  primary  induced  current, 
•or  current  of  the  first  coil,  is  generated;  h,  spring-hammer  or  vibrator;  m,  a  piece  of  soft  iron 
becoming  a  magnet  when  the  current  is  passing ;  2c,  outer  coil  in  which  the  secondary  induced 
current,  or  current  of  the  second  coil,  is  generated  ;  P,  handles  of  inner  coil ;  f,  handles  of  outer  coil- 

correctly  mark  poles  +  and  — ,  but  that  the  current  of  the  second  coil  runs 
in  both  directions,  so  that  any  designation  of  its  handles  as  positive  and  neg- 
ative is  incorrect.  The  only  justification  for  the  marking  of  the  secondary 
or  outer  current  poles,  as  is  often  done,  is  found  in  the  fact  that  the  induced 
current  of  the  broken  circuit  is  stronger  than  that  of  the  closed  circuit. 
Hence  it  is  that  with  very  strong  currents  the  two  poles  can  sometimes  be 
distinguished  when  grasped  in  the  hand.  The  difference  is,  however,  a 
slight  one,  and  for  all  practical  purposes  the  induced  current  of  the  outer 
coil  is  a  to-and-fro  one,  without  any  negative  or  positive  poles. 

If  a  strong  continuous  galvanic  current  be  passed  through  a  person,  a 
shock  is  felt  at  the  moment  of  making  and  breaking  the  circuit,  but  while 
the  current  is  passing  no  sensation  is  perceived  except  at  the  points  of 
entrance  and  exit.  Or  if  the  current  be  passed  through  the  nerve  of  a 
muscle,  that  muscle  violently  contracts  at  the  moment  the  circuit  is  made 
or  broken,  but  while  the  current  is  flowing  is  quiescent.  If  a  rapidly 
interrupted  faradic  current  be  passed  through  a  nerve,  the  muscle  supplied 
by  that  nerve  is  thrown  into  a  continuous  spasm.  The  reason  of  this  is 


ELECTRICITY.  49 

obvious.  The  so-called  faradic  or  induced  current  is,  as  has  already  been 
stated,  a  succession  of  instantaneous  broken  currents  for  the  first  coil,  and 
of  equally  brief  to-and-fro  currents  for  the  outer  coil ;  so  that  the  circuit 
is  continually  being  closed  and  broken,  and  the  muscle  is  continually 
excited  to  action.  There  is,  therefore,  a  different  result  achieved  in  the 
application  of  the  continuous  and  induced  currents,  not  because  there  is 
any  real  difference  in  their  natures,  but  because  the  mode  of  application 
is  diverse. 

Many  medical  electricians  teach  that  the  true  galvanic  current  is  very 
different  from  the  faradic  current,  and  many,  like  Duchenne,  persist  in 
asserting  that  the  currents  of  the  first  coil  are  essentially  different  from 
those  of  the  second.  Galvanism  is,  however,  galvanism,  and  its  nature 
and  attributes  are  probably  always  the  same.  The  apparent  differences  in 
results  are  simply  due  to  the  variations  in  the  power,  the  duration,  and  the 
direction  of  the  currents.  The  ordinary  faradic  currents  lack  chemical 
power  because  they  pass  so  quickly  that  they  have  not  time  to  exert  a 
chemical  influence.  When,  however,  by  proper  apparatus  the  to-and-fro 
currents  of  the  ordinary  faradic  machine  are  separated,  and  the  interrup- 
tions made  so  rapid  that  the  breaks  are  too  short  to  exert  influence,  all 
the  chemical  and  vital  effects  of  the  continuous  current  running  in  one 
direction  are  obtained.  It  is  by  virtue  of  this  fact  that  ordinary  street- 
currents,  which  are  all  currents  of  induction,  may  be  used  in  human  medi- 
cine in  lieu  of  the  direct  galvanic  current. 

We  can  readily,  by  mechanical  means  and  contrivances,  interrupt  the 
continuous  current,  or  even  rapidly  reverse  the  poles  so  as  to  give  a  to- 
and-fro  current  like  that  of  the  outer  coil.  When  this  is  done,  it  is  im- 
possible to  distinguish  between  the  action  of  the  galvanic  and  that  of  the 
faradic  current  in  producing  muscular  contractions.  It  is  true  that  in  cer- 
tain diseased  states  of  the  muscle  it  has  been  asserted,  and  with  apparent 
reason,  that  the  action  of  the  induced  current  is  essentially  different  from 
that  of  the  true  galvanic  current.  *  But  we  believe  further  investigation  will 
show  that  the  seeming  differences  are  really  due  to  the  difference  in  the 

*  It  is  this  fact  that  has  led  to  the  belief  that  there  is  some  intrinsic  and  inscrutable 
difference  between  the  induced  current  and  the  chemical  current.  But  time  is  an  ele- 
ment required  for  the  propagation  of  any  force.  If  the  hand  be  passed  rapidly  through 
a  flame,  the  latter  is  not  felt ;  if  the  hand  move  more  slowly,  a  sensation  of  warmth  is 
perceived  ;  if  the  motion  be  still  slower,  this  sensation  becomes  pain.  Now,  if  the  hand 
be  partially  anaesthetic  from  disease,  in  order  for  the  sensation  of  warmth  to  be  perceived 
motion  must  be  much  slower  than  in  the  first  instance.  In  other  words,  more  time  is 
required  for  the  partially  paralyzed  sensory  nerve  to  perceive  heat  than  for  the  normal 
nerve  to  do  so.  What  is  true  of  the  sensory  nerve  is  true  also  of  the  motor  nerve.  It 
does  not  respond  so  quickly  to  stimuli  when  partially  paralyzed  as  when  normal.  The 
muscle  first  loses  its  power  of  responding  to  those  faradic  currents  which  are  excessively 
rapid,  then  to  those  which  are  less  so,  and  finally  to  all  induced  currents,  because  from 
their  very  nature  these  currents,  even  when  slowest,  last  but  a  fraction  of  a  second.  The 
chemical  current  may  be  continued  for  any  length  of  time  at  the  will  of  the  operator,  who 
is  thus  enabled  to  act  upon  a  muscle  whose  nerve  has  become  so  insensitive  that  it  fails 
to  perceive  the  flash  of  faradic  galvanism.  The  probable  correctness  of  this  theory  is 
shown  by  the  fact  that  the  rapidly  interrupted  chemical  current  is  no  more  able  to  affect 
the  diseased  muscle  than  is  the  rapidly  interrupted  faradic  current. 

4 


50  ELECTRICITY. 

lengths  of  time  during  which  the  currents  are  passing,  and  not  to  any 
inherent  peculiarities  of  the  various  currents  themselves. 

It  is  of  the  utmost  importance  to  determine  by  what  route  or  routes 
galvanic  currents  pass  through  the  body  when  the  poles  are  applied  to  it, 
and,  since  the  body  as  a  galvanic  conductor  is  governed  by  ordinary 
physical  laws,  some  knowledge  of  these  laws  is  a  necessity  to  the  electro- 
therapeutist. 

If  a  current  be  passing  along  a  homogeneous  conductor,  such  as  a  wire 
of  iron,  of  copper,  or  of  other  metal,  and  that  conductor  splits  up  into  a 
number  of  branches,  the  current  also  divides,  as  is  illustrated  in  the  dia- 
gram (Fig.  3).  If  these  branches,  being  of 
equal  size  and  length,  offer  an  equal  resist- 
ance, the  current  divides  equally  ;  but  if 
the  size  or  length,  and  consequently  the 
resistance,  of  the  branches  be  unequal,  the 
division  of  the  current  is  unequal  ;  the 
law  being  that  the  strength  of  the  current 

— fi +— <^-\ ^/          in    each   branch   of   the   conductor  is    in- 
versely proportional   to  the   resistance  of 

that  branch.  This  law  is  as  applicable  to  conductors  composed  of  many 
substances  as  to  those  composed  of  a  single  substance  ;  but  then  the 
resistance  in  a  branch  depends  upon  the  specific  resistance  of  the  sub- 
stance of  which  it  is  composed,  as  well  as  upon  its  size  and  length. 

In  applying  these  laws  to  the  passage  of  galvanism  through  the  body, 
it  must  be  borne  in  mind  that  the  dry  skin  offers  an  enormous  resistance 
to  the  passage  of  the  current,  so  that  practically  none  of  the  latter  will 
pass  along  it.  On  the  other  hand,  when  the  skin  is  thoroughly  wet  with 
salt  water  it  allows  the  current  to  pass  through  it  readily. 

Let  us  suppose,  then,  that  in  the  diagram  (Fig.  4)  -\- p  and — p  = 
wetted  poles  ;  ss  =  skin,  with  the  tissues  below  it.  It  is  evident  that,  if 
the  tissues  were  a  uniform  mass,  the  current,  passing  through  the  skin  as 
a  solid  bolt,  would  break  up  into  an  infinite  number  of  curved  currents, 
which  would  meet  and  pass  through  the  skin  again  as  a  solid  mass  at  — p. 
It  is  equally  plain  that,  of  these  sub-currents,  those  whose  course  was 
nearest  the  straight  line  from 
+  p  to  —  p  would  be  the 
shortest,  and  would,  therefore, 
meeting  with  the  least  resist- 
ance, be  the  strongest,  while 
as  the  curve  and  consequently 
the  length  and  the  resistance 
increased,  the  strength  of  the 
current  would  diminish  until  it 

became  practically  null.  In  this  imaginary  case  the  tissue  beneath  the 
skin  has  been  supposed  to  be  homogeneous  :  in  actual  life  the  tissue 
never  is  homogeneous,  and  the  resistance  of  the  different  constituents 


ELECTRICITY.  51 

varies  somewhat.  Consequently,  the  strength  of  the  subdivisions  of  the 
current  is  modified, — those  branch  streams  being  increased  which  run 
along  or  through  tissues  that  conduct  readily,  and  vice  versa, 

By  remembering  these  facts,  we  are  enabled  to  apply  electricity  as 
closely  as  may  be  to  any  desired  portions  of  the  body.  Thus,  if  it  be 
intended  to  affect  as  exclusively  as  possible  a  certain  spot  or  minute  por- 
tion of  a  nerve,  a  well-wetted  small  electrode  is  placed  directly  over  this 
portion,  and,  especially  if  the  nerve  be  somewhat  deeply  situated,  pressed 
down  firmly,  so  as  to  condense  the  tissues  as  far  as  possible  into  a  homo- 
geneous mass,  while  a  large  wet  electrode  is  placed  at  a  small  distance 
from  it  in  a  situation  which  the  anatomy  of  the  part  will  readily  suggest. 
The  diagram  (Fig.  5)  will  perhaps  illustrate  this  point  more  clearly  than 

would  many  words. 

FIG.  5. 


It  is  evident  that  the  spot  immediately  under  the  small  electrode  will 
receive  the  full  strength  of  the  current,  which  is  directly  afterwards  so 
broken  up  as  to  affect  very  slightly  any  other  part. 

Again,  suppose  it  is  desired  to  pass  a  current  through  some  length  of 
a  nerve  ;  it  is  evident,  in  the  first  place,  that  two  small  electrodes  should 
be  chosen,  and  that  they  should  be  well  wetted  and  pressed  firmly  upon 
the  trunk  of  the  nerve  at  the  two  ends  of  that  portion  which  is  to  be 
affected.  Again,  in  applying  electric  currents  to  muscles  it  is  found  that 
if  the  currents  be  sent  through  the  body  of  the  muscles,  only  very  imper- 
fect and  partial  contractions  occur,  unless,  indeed,  the  currents  be  exces- 
sively strong.  Duchenne  was  the  first  to  discover  that  when  one  pole  is 
placed  over  certain  spots  or  points  in  the  muscle,  violent  general  spasms 
of  the  muscle  are  produced  by  currents  usually  too  feeble  to  elicit  a  dis- 
tinct response.  To  these  places  the  name  of  motor  points  has  been  given. 
These  motor  points  correspond  to  the  position  at  which  the  supplying 
nerve  enters  the  muscle.  When  it  is  desirable  to  affect  chiefly  or  solely  a 
given  motor  point,  it  is  evident  that  one  small  well-wetted  electrode  should 
be  pressed  firmly  over  the  motor  point,  and  another  large  sponge  elec- 
trode placed  at  some  little  distance  from  it,  in  the  manner  which  has 
already  been  explained. 

For  certain  purposes,  to  be  hereafter  detailed,  it  is  often  desirable  to 


52  ELECTRICITY. 

affect  chiefly  the  skin  by  the  electric  current.  Under  these  circumstances 
the  skin  should  be  well  dried.  It  then  offers  so  great  a  resistance  that 
only  currents  of  considerable  strength  are  able  to  force  their  way  through, 
and  even  these  currents,  taking  advantage  of  the  natural  apertures  formed 
by  the  sweat-  and  other  glands,  are  broken  up  into  a  number  of  branch 
currents.  The  galvanic  current  reaches  the  internal  structures  in  a  great 
number  of  small  streams  very  much  reduced  in  power  by  the  resistance 
they  have  overcome.  If  the  second  pole  of  the  battery  be  a  large  well- 
wetted  disk  or  sponge  at  a  distant  part  of  the  body,  it  is  evident  that 
these  branch  currents  will  separate  and  subdivide  in  such  a  way  that  their 
effect  upon  the  deeper  structures  will  be  almost  entirely  lost. 

Ohm's  law  does  not  govern  electricity  upon  points,  since  the  force 
accumulates  on  the  extreme  end  of  the  point  until  its  density  is  excessive, 
and  its  self- repulsive  power  becomes  so  great  as  to  overcome  all  resistance 
and  to  break  off  highly  electrified  particles  of  the  conductor,  which  fly 
off  through  the  air.  It  is  this  that  renders  the  so-called  "  electric  brush" 
so  energetic  in  its  action  on  the  skin.  This  instrument  consists  of  a  number 
of  wires  united  in  the  form  of  a  cylindrical  brush  and  connected  with  one 
pole  of  the  battery  ;  when  this  is  brought  in  contact  with  the  skin  of  a  person, 
on  whom  at  some  distance  is  placed  the  other  large  well-wetted  electrode, 
each  wire  point  offers  a  dense  accumulation  of  electricity,  which  forces  its 
way  at  all  hazards  through  a  minute  portion  of  the  skin.  The  whole  current, 
of  course,  enters  the  deeper  tissue  in  an  infinite  number  of  subdivisions, 
and  consequently  its  effect  on  these  tissues  is  reduced  to  a  minimum. 

THERAPEUTIC  APPLICATION. — Most  of  the  therapeutic  applications 
of  electricity  are  considered  in  this  book  under  special  headings,  but  it 
seems  proper  at  this  place  to  call  attention  to  the  use  of  the  current  for 
the  relief  of  various  local  rheumatic  affections.  In  subacute  or  chronic 
muscular  rheumatism  faradization  is  often  of  great  service,  and  even  in 
rheumatic  diseases  of  the  joints  it  sometimes  brings  marked  relief.  When 
the  symptoms  are  acutely  inflammatory  they  must  first  be  subdued  by 
suitable  measures  ;  but  when  they  are  subacute  the  current  may  be  em- 
ployed at  the  beginning  of  the  attack.  It  should  be  rapidly  interrupted 
and  as  strong  as  can  be  borne  by  the  patient.  The  first  seance  should 
last  but  five  minutes,  but  the  time  of  application  can  be  gradually  pro- 
tracted to  fifteen  or  twenty  minutes. 

Motor  System. — Galvanic  currents  are  employed  in  paralytic  affections 
for  three  distinct  purposes, — namely,  diagnosis,  prognosis,  and  therapeusis. 
These  we  shall  consider  in  the  order  in  which  they  have  been  named. 

There  are  certain  palsies,  such  as  pseudo-muscular  hypertrophy,  in 
which  the  muscular  structure  is  so  destroyed  independently  of  any  involve- 
ment of  the  nervous  system  that  no  response  to  the  galvanic  current  is 
possible.  All  of  these  palsies  are,  however,  essentially  exceedingly  chronic, 
and  their  diagnosis  is  to  be  made  out  chiefly  by  a  microscopical  exami- 
nation of  the  muscles  themselves.  When  a  paralysis  is  due  to  lesion  in 
the  brain  or  in  those  portions  of  the  spinal  cord  which  have  no  trophic 


ELECTRICITY.  53 

influence,  no  changes  occur  in  the  muscle  except  the  very  gradual  altera- 
tions due  to  disuse.  On  the  other  hand,  if,  by  disease  of  the  trophic  cell 
in  the  spinal  cord,  or  by  disease  or  injury  of  a  conducting  nerve,  a  muscle 
is  entirely  deprived  of  the  influence  of  the  spinal  centres  it  rapidly  under- 
goes structural  change.  When  a  muscle  is  degenerating  for  want  of  spinal 
influence,  it  first  loses  its  power  of  responding  to  rapidly  interrupted  faradic 
or  chemical  currents,  then  to  slowly  interrupted  faradic  currents,  then  to 
slowly  interrupted  chemical  currents,  and  lastly  to  slowly  reversed  chem- 
ical currents.  During  this  period  of  degeneration  it  is  possible  to  elicit 
with  the  galvanic  current  the  so-called  reaction  of  degeneration,  first  dis- 
covered by  Brenner.  To  demonstrate  these  reactions  it  is  essential  to 
apply  the  electrode  to  the  muscle  :  if  the  electrode  be  connected  with  a 
nerve-trunk  of  a  degenerating  muscle  it  will  be  found  that  reaction  is 
diminished  in  quantity  but  not  altered  in  quality.  When  a  feeble  gal- 
vanic current  is  used,  and  the  negative  pole  (cathode)  placed  over  the 
normal  .muscle  but  not  over  its  motor  point,  a  strong  contraction  occurs 
at  the  closure  of  the  circuit  ;  when,  however,  the  positive  pole  (anode) 
is  placed  over  the  normal  muscle,  the  contraction  is  much  less  ;  in  neither 
case  is  there  any  contraction  when  the  circuit  is  broken  :  in  other  words, 
with  the  normal  muscle  and  a  feeble  current  we  obtain  good  cathodal 
closing  contraction,  slight  anodal  closing  contraction,  and  no  motion 
whatever  at  either  cathodal  opening  or  anodal  opening.  When  a  current 
of  sufficient  power  is  used,  opening  contractions  are  produced,  and  the 
anodal  contraction  is  greater  than  the  cathodal.  The  reaction  of  degenera- 
tion consists  merely  in  a  more  or  less  perfect  reversal  of  the  above  formula. 
The  anodal  (positive  pole)  closure  then  causes  a  stronger  contraction 
than  the  cathodal  (negative  pole)  closure.  When  there  is  only  a  slight 
degree  of  degeneration  present,  there  is  a  correspondingly  slight  increase 
of  anodal  closing  over  cathodal  closing  contraction.  A  minimum  degenera- 
tion would  be  indicated  by  an  equality  of  the  two  closing  contractions. 

These  alterations  in  the  electrical  relations  of  a  degenerating  muscle 
may  be  formulated,  and  in  this  way  are  perhaps  more  readily  grasped 
by  the  student.  The  symbols  are  as  follows  :  An  Cl  C  represents  anodal 
closing  contraction ;  An  O  C  represents  anodal  opening  contraction  / 
Ca  Cl  C  represents  cathodal  closing  contraction;  Ca  O  C  represents 
cathodal  opening  contraction  ;  <  represents  is  less  than  ;  >  represents  is 
more  than  (the  point  of  the  <  being  towards  the  lesser  quantity).  Then 
the  formulas  are  : 

An  Cl  C  <  Ca  Cl  C 


A     r\  r-  \  r-    ^  r*  i  muscle  normal. 
An  O  C  >  Ca  O  C  ) 

An  Cl  C  =  Ca  Cl  C  )  .    .    ..     fi 

nrl  musc'e  m  the  nrst  stage  of  degeneration. 

x\n  v_/     v-  —  v_^cl  v_y    V^  ) 

An  Cl  C  >  Ca  Cl  C  |  muscle  in  a  more  advanced  stage  of  degenera- 
An  O  C  <  Ca  O  C  j      tion. 

After  the  latter  reactions  of  degeneration  (De   R  of  some  authors) 
have  been  established,  if  the  muscle  continues  to  undergo  change,  the 


54  ELECTRICITY. 

galvanic  irritability  slowly  diminishes,  stronger  and  stronger  currents  being 
required  to  produce  an  effect.  When  a  certain  stage  is  reached,  all  reac- 
tions cease,  save  a  feeble  An  Cl  C,  and  at  last  this  is  lost  and  the  muscle 
does  not  respond  at  all.  When  recovery  occurs,  the  electrical  reactions 
of  the  muscle  pass  upward  along  the  pathway  they  have  descended. 

The  practical  importance  of  the  reaction  of  degeneration  is  greatly 
lessened  by  the  circumstance  that  its  demonstration  usually  requires  much 
skill  and  patience,*  and  that  it  probably  is  never  present  when  a  muscle 
still  retains  its  integrity  as  regards  the  faradic  current.  For  the  purposes 
of  the  practitioner,  the  failure  of  response  to  the  latter  current  is  the  best 
test  as  to  the  condition  of  a  muscle.  When  a  muscle  loses  its  power  of 
responding  to  the  rapidly  interrupted  faradic  current  in  a  week  or  ten  days 
after  the  occurrence  of  paralysis,  whether  the  reaction  of  degeneration 
can  or  cannot  be  satisfactorily  demonstrated,  the  inference  is  very  positive 
that  the  lesion  either  is  one  of  the  nerve-trunk  or,  if  of  a  nerve-centre,  is 
of  such  a  character  as  seriously  to  involve  the  trophic  cells  of  the  spinal 
cord.  If  a  few  days  later  such  muscle  is  unable  to  respond  to  any  faradic 
current,  this  inference  becomes  a  certainty.  Under  these  circumstances, 
the  possible  lesion  is  narrowed  down  to  poliomyelitis,  a  conceivable  de- 
structive myelitis,  and  an  affection  of  a  nerve-trunk. 

The  persistence  of  muscular  contractility  intact  for  some  weeks  after 
the  occurrence  of  a  palsy  depending  upon  an  organic  lesion  proves  that 
the  disease  is  of  cerebral  origin,  or,  being  spinal,  is  of  such  nature  as  not 
to  compromise  seriously  the  trophic  nerves  of  the  cord. 

In  applying  these  rules,  it  must  not  be  forgotten  that  whenever  a 
muscle  is  not  used  it  loses  its  contractile  power,  so  that  even  in  paralysis 
from  cerebral  hemorrhages  the  muscles  finally  degenerate,  although  this 
degeneration  is  rarely  so  complete  as  in  peripheral  palsies.  It  is  not  the 
fact  of  degeneration,  but  its  degree,  and  especially  the  period  of  time 
which  elapses  between  its  occurrence  and  the  commencement  of  the 
paralysis,  that  is  the  important  factor  in  the  diagnosis.  In  cerebral  palsies 
no  distinct  loss  of  functional  activity  in  the  muscles  is  usually  perceived 
sooner  than  six  weeks  after  the  onset  of  the  attack  ;  and  even  after  years 
have  elapsed  some  response  may  often  be  elicited  by  strong  slowly  inter- 
rupted or  reversed  currents. 

There  are  certain  palsies  in  which  the  electro-muscular  contractility  is 
really  or  apparently  above  normal.  Very  frequently  the  excessive  contrac- 
tions produced  are  not  so  marked  in  the  muscles  to  which  the  currents  are 
applied  as  in  other  muscles,  whose  movements  are  in  reality  reflex  in  their 
nature.  In  all  these  cases  the  probabilities  are  that  there  is  a  condition 
of  acute  hyperaemia  or  of  excessive  functional  irritability  of  the  spinal  cord. 

In  hysterical  paralysis  any  aid  to  diagnosis  is  often  of   very  great 

*  In  attempting  to  bring  out  the  reaction,  the  clock-work  current-breaker  as  usually 
furnished  by  instrument-makers  is  useless  ;  the  hand  current-breaker  may  be  employed, 
but  almost  requires  an  assistant.  Hence  some  electricians  use  a  pedal  rheotome,  which 
enables  the  operator  to  cut  off  the  current  without  moving  his  hands. 


ELECTRICITY.  55 

value,  and  it  has  been  asserted  that  in  this  class  of  palsies  the  preser- 
vation of  electro-contractility  with  loss  of  electro-sensibility  is  always 
present,  and  is  of  diagnostic  import.  Our  experience,  nevertheless,  is 
very  positive  that  in  hysterical  palsy  both  electro-contractility  and  electro- 
sensibility  are  frequently  normal.  When,  however,  the  paralyzed  muscle 
responds  to  galvanic  currents,  and  the  patient  is  to  a  great  extent,  or 
altogether,  insensible  to  their  passage,  a  very  positive  diagnosis  of  hysteria 
may  be  given.  The  electro-contractility  is  never  seriously  compromised 
in  hysterical  palsy. 

In  using  galvanism  as  an  aid  in  prognosis,  the  condition  of  the  mus- 
cular contractility  is  always  to  be  considered  in  conjunction  with  the  nature 
of  the  lesion  and  the  length  of  time  it  has  existed. 

Taking  first  ordinary  hemiplegia  as  the  type  of  cerebral  palsies,  it  must 
be  borne  in  mind  that  the  actual  existent  amount  of  paralysis  is  really  the 
product  of  two  essentially  different  factors.  The  nerve-centre  is  primarily 
damaged,  and  after  a  time  the  muscle  also  suffers  loss  of  structural  in- 
tegrity from  want  of  use.  The  restoration  of  the  nerve-centre  does  not 
necessarily  involve  the  restoration  of  the  muscle,  so  that  in  a  case  of  hemi- 
plegia of  some  standing  the  cerebrum  may  have  recovered  itself  partially 
or  entirely,  and  yet  the  muscle  be  in  such  a  state  of  degeneration  as  to  be 
unable  to  respond  to  the  impulse  transmitted  to  it  from  the  nerve-centre. 

Under  these  circumstances,  galvanic  treatment,  although  unable  to 
affect  the  nerve-centres  to  any  extent,  does  great  good  by  restoring  the 
muscular  tone.  It  is  manifestly  impossible  in  such  a  case  to  determine 
before  treatment  how  far  the  nerve-centre  has  recovered  itself,  or,  in  other 
words,  to  what  extent  the  existing  paralysis  is  of  centric  and  to  what 
extent  of  muscular  origin.  When,  in  a  case  of  apoplectic  hemiplegia, 
there  is  no  recovery  of  the  power  of  voluntary  movement  after  the 
lapse  of  six  weeks,  the  prospect  of  decided  improvement  from  electrical 
treatment  is  very  gloomy,  because  the  probabilities  are  altogether  in  favor 
of  the  existence  of  a  serious,  persistent  centric  lesion.  If,  however,  there 
is  some  motion,  the  probabilities  of  improvement  are  inversely  propor- 
tionate to  the  structural  health  of  the  muscles, — i.e.,  the  worse  the  state 
of  the  muscle  the  better  the  expectation  of  relief.  If  the  tone  and  the 
electro-contractility  of  the  muscles  are  normal,  the  centric  factor  is  the 
chief  one  in  the  production  of  the  paralysis,  and  little  good  is  to  be 
achieved  by  the  use  of  the  galvanic  current.  On  the  other  hand,  if  the 
muscles  have  undergone  a  very  decided  degeneration,  much  good  is  to  be 
expected.  No  hopes  of  absolute  cure  should,  however,  be  held  out,  be- 
cause, in  the  great  majority  of  cases,  after  the  muscles  have  been  fully 
restored  the  nerve-centre  is  found  to  be  more  or  less  damaged.  The  im- 
provement under  the  use  of  electricity  is  usually  at  first  rapid,  but  after  a 
time  ceases  altogether,  because,  the  muscles  having  recovered  their  tone, 
it  is  not  possible  to  affect  to  any  great  extent  the  sole  remaining  cause  of 
the  paralysis, — i.e. ,  the  centric  lesion.  Under  these  circumstances  it  is 
useless  to  continue  treatment. 


56  ELECTRICITY. 

In  poliomyelitis,  early  in  the  attack  the  galvanic  current  is  of 
little  value  in  determining  the  prognosis,  except  that  the  general  law  is, 
that  the  more  rapidly  electro- contractility  is  lost  the  more  serious  is  the 
case.  In  advanced  cases  the  duration  of  the  attack  and  the  condition  of 
the  electro-contractility  in  the  muscles  are  both  to  be  considered.  If  no 
response  to  an  electric  current  can  be  obtained,  the  prognosis  is  always 
very  grave  ;  although  even  under  such  circumstances  a  decided  improve- 
ment has  occurred  in  a  small  percentage  of  the  cases  we  have  treated.  If 
the  case  be  an  old  one,  the  preservation  of  some  degree  of  electro-contrac- 
tility indicates  that  the  structural  lesion  in  the  cord  is  not  a  fatal  one  ;  and 
as,  under  these  circumstances,  the  muscles  can  always  be  more  or  less  per- 
fectly restored,  the  prospect  of  improvement  is  very  good.  The  preserva- 
tion of  electro-contractility  late  in  the  disorder,  when  the  centric  lesion  is  no 
longer  progressing,  is  of  much  more  import  than  it  is  in  the  first  few  weeks 
or  months  of  the  case,  when  the  central  trouble  may  be  increasing. 

In  peripheral palsies  the  prognosis  depends  upon  the  nature  of  the 
nwve-lesion  rather  than  upon  the  condition  of  the  muscle  ;  but  it  must  be 
remembered  that  when  a  muscle  has  absolutely  lost  its  power  of  respond- 
ing to  any  electrical  current  its  restoration  is  always  a  matter  of  difficulty 
and  of  some  doubt. 

In  regard  to  therapeusis,  the  first  point  to  be  determined  in  acute  cases 
is,  very  often,  when  to  commence  electrical  treatment.  When  the  lesion 
is  of  such  nature  as  not  to  provoke  any  irritation  of  the  nerve-centre,  no 
time  should  be  lost.  Thus,  if  a  man  is  unable  to  use  his  arm  because 
he  has  slept  with  it  under  his  head  and  thereby  paralyzed  the  nerve  by 
pressure,  galvanism  should  be  at  once  employed. 

When,  however,  the  lesion  is  of  such  character  as  of  necessity  to  irri- 
tate the  nerve-centres,  the  case  is  different.  The  local  stimulation  of  the 
peripheral  nerve-fibres  by  the  electrical  current  does,  in  some  way  not  yet 
definitely  understood,  affect  the  nutrition  of  the  nerve-centres  ;  and  when 
these  nerve-centres  are  in  a  state  of  active  excitement  or  inflammation,  a 
peripheral  galvanic  irritation  may  do  serious  injury.  Hence  the  rule  that 
when  an  acute  palsy  is  connected  with  active  irritation  of  the  nerve-cen- 
tres, galvanism  should  not  be  used  upon  the  muscles  until  the  centric  dis- 
turbance has  subsided.  Thus,  in  hemiplegia  from  cerebral  hemorrhage 
the  muscles  must  be  allowed  to  rest  not  only  until  all  symptoms  of  centric 
irritation  have  passed  away,  but  also  until  the  brain  has  become  so  accus- 
tomed to  the  clot  that  the  latter  no  longer  acts  as  a  foreign  body.  It  is 
usually  from  three  to  six  weeks  before  electricity  can  be  used  with  advan- 
tage in  these  cases.  Again,  in  acute  cerebritis,  cerebral  or  spinal  menin- 
gitis, and  myelitis,  the  employment  of  galvanic  currents  should  be  strictly 
forbidden  until  a  stage  is  reached  when  the  effects  of  the  inflammation,  and 
not  the  inflammation  itself,  are  to  be  dealt  with. 

When  it  has  been  decided  to  commence  the  use  of  electricity,  it  is  next 
to  be  determined  what  current  shall  be  employed.  It  has  already  been 
shown  that  there  are  no  inherent  mysterious  differences  in  the  various 


ELECTRICITY.  57 

currents  ;  yet  there  is  a  practical  difference,  and  the  clinical  rule  of  choice 
is,  Always  select  that  current  which  produces  the  greatest  amount  of  muscu- 
lar contraction  with  the  least  amount  of  pain ;  trying  the  rapidly  inter- 
rupted faradic  or  the  rapidly  interrupted  chemical  current  and  the  slowly 
interrupted  faradic  or  the  slowly  interrupted  chemical  current,  and  always, 
when  these  fail  to  elicit  response,  the  slowly  reversed  chemical  current, 
which,  if  necessary,  may  be  increased  in  strength  until  the  patient  can  no 
longer  bear  the  pain. 

The  current  having  been  selected,  the  individual  muscles  must  be  gal- 
vanized at  each  seance. 

After  what  has  been  said,  it  is  not  necessary  to  speak  at  this  point 
as  to  the  best  methods  of  applying  the  currents  to  the  muscles,  but  only 
to  insist  upon  the  fact  that  it  is  not  so  much  the  electricity  as  the  con- 
tractions induced  by  it  that  benefit  the  palsied  parts,  and  that  conse- 
quently the  electro-motor  points  of  the  muscles  should  always  be  sepa- 
rately reached.  The  diagrams  given  in  the  Appendix  will  point  out  more 
clearly  than  would  any  description  the  approximate  positions  of  the  motor 
points,  which  vary  somewhat  in  their  location  in  various  individuals. 
Some  deep-seated  muscles  we  are  not  able  to  reach  directly,  but  we  can 
reach  them  indirectly  by  galvanizing  the  nerves  which  supply  them. 

There  are  certain  precautionary  rules  which  must  never  be  lost  sight 
of  in  the  electrical  treatment  of  palsies.  Pain  is  an  evil,  and  its  infliction 
is  always  to  be  avoided  as  far  as  possible.  Hence  the  rule  never  to  use 
stronger  currents  than  is  necessary.  It  is  very  possible  to  fatigue  a  healthy 
muscle,  much  more  a  diseased  one.  A  weak  muscle  may  be  greatly  in- 
jured by  being  over-fatigued.  Hence  the  rule  that  currents  are  not  to  be 
applied  to  muscles  sufficiently  long  at  a  time  to  induce  fatigue.  In  gen- 
eral, an  electrical  stance  should  last  from  ten  to  twenty  minutes,  no  one 
muscle  being  subjected  to  the  currents  for  more  than  five  minutes,  and  it 
may  be  repeated  daily,  or  three  times  a  week. 

Sensory  System. — Affections  of  the  sensory  nerves  are  of  three  kinds, 
— pain,  hypersesthesia,  and  anaesthesia.  The  use  of  electricity  for  the 
relief  of  these  disorders  is  almost  entirely  empirical, — indeed,  is  often 
purely  experimental  in  an  individual  case,  as  no  clinical  laws  regulating 
the  use  or  enabling  us  to  decide  as  to  the  applicability  of  the  agency  have 
as  yet  been  worked  out. 

It  may  be  laid  down,  however,  as  an  axiom,  that  the  galvanic  current 
is  powerless  to  relieve  the  pain  of  phlegmonous  inflammations,  and  that 
its  use  should  be  restricted  chiefly  to  nervous  pain  or  neuralgia.  It  is  also 
true  that  the  currents  are  possessed  of  no  therapeutic  power  over  neural- 
gia dependent  upon  central  organic  lesions  ;  this  is  also  probably  true  of 
such  neuralgias  as  migraine,  malarial  hemicrania,  and  some  toxic  neu- 
ralgias, in  which,  although  there  is  no  perceptible  organic  lesion,  there 
is  some  deep-seated,  inherent  deficiency  either  in  the  central  nervous 
system  or  in  the  constitution  or  condition  of  the  patient. 

When,   as  in  sciatica,   the  so-called  neuralgia  is  due  to  a  neuritis, 


58  ELECTRICITY. 

galvanism  may  be  of  great  service.  It  should  not  be  applied,  however, 
until  the  stage  of  very  acute  inflammation  is  past.  In  regard  to  the 
selection  of  the  current,  our  experience  is  that  it  must  be  purely  em- 
pirical. The  most  usually  successful  is  a  very  mild  (four  to  eight  cells) 
chemical  current,  which  should  be  passed  steadily  for  ten  minutes  down 
the  nerves.  It  should  not  be  so  strong  as  to  give  actual  pain,  and  must 
not  be  interrupted.  As  in  the  great  majority  of  cases  this  method  of 
application  yields  the  best  results,  it  should  always  be  tried  first.  When 
it  does  good,  it  nearly  always  affords  relief  during  the  passage  of  the 
current,  at  once  or  after,  at  the  most,  two  or  three  sittings.  Further, 
the  period  of  relief  soon  begins  to  extend  beyond  the  seance  and  gradually 
grows  longer  and  longer.  Some  cases  receive  most  benefit  from  a  rapidly 
interrupted  faradic  current,  which  should  therefore  be  tried  if  the  continu- 
ous current  fails.  To  the  employment  of  electricity  should,  of  course, 
always  be  added  the  proper  local  and  constitutional  treatment  of  the  case. 

In  hysteria,  in  some  cases  whose  nature  is  very  obscure,  and  rarely  as 
a  sequela  or  result  of  a  serious  cerebral  or  spinal  lesion  which  may  have 
been  more  or  less  completely  recovered  from,  there  exist  local  anesthesias 
of  the  skin.  When  these  are  not  dependent  upon  a  too  serious  organic 
lesion,  they  are  often  very  much  benefited,  or  even  cured,  by  the  use  of 
the  electric  brush.  This  should  be  large  and  composed  of  fine  wires, 
while  the  other  electrode  should  consist  of  a  large,  well-wetted  sponge, 
placed  upon  a  distant  part  of  the  body.  Either  the  faradic  or  the  chemical 
current  may  be  employed  ;  in  either  case  it  should  be  a  very  strong  one. 
Toxaemic  anaesthesias,  such  as  those  sometimes  produced  by  arsenic, 
we  have  seen  benefited  by  electrical  treatment  with  the  dry  brush. 

APPLICATION  TO  THE  NERVE-CENTRES,  AND  USE  AS  A  TONIC. — 
Galvanism  in  various  forms  has  been  applied  locally  to  the  nerve-centres 
in  various  diseases.  In  regard  to  the  brain,  we  have  never  yet  met  with  any 
clear  clinical  evidence  of  good  having  been  accomplished  ;  and,  with  our 
present  physiological  knowledge,  it  is  difficult  to  imagine  in  what  way  or 
under  what  circumstances  cerebral  galvanization  can  produce  good  results. 
On  the  other  hand,  harm  certainly  has  been  wrought  by  the  application 
of  strong  currents  to  the  head.  Galvanic  currents  passed  through  the 
brain  can  act  only  as  irritants,  and  we  agree  entirely  with  the  dictum  of 
Cyon  {Principes  <?  Electrotherapie,  Paris,  1873),  that  galvanization  of  the 
head  ought  to  be  abandoned. 

An  enormous  amount  of  influence  in  all  sorts  of  diseases  has  been 
claimed  for  the  so-called  galvanization  of  the  cervical  sympathetic.  The 
situation,  however,  of  the  upper  ganglion  deep  beneath  the  carotid  artery 
makes  it  extremely  improbable  that  it  can  be  reached  by  any  suitable 
galvanic  current  from  the  outside  ;  and  the  fact  is  that  it  is  impossible 
by  means  of  therapeutic  currents  to  produce  any  stimulation  of  the  gan- 
glion sufficient  to  call  forth  the  slightest  manifestation  of  functional 
activity.  What  is  true  of  the  galvanization  of  the  sympathetic  nerve  is 
equally  true  of  the  galvanization  of  the  spinal  cord.  It  is  not  possible 


ELECTRICITY.  59 

by  therapeutic  currents  to  affect  either  of  these  nerve-centres  from  the 
exterior  of  the  body.* 

The  faradic  current  is  without  doubt,  when  properly  applied,  capable 
of  acting  as  a  general  stimulant  to  the  circulation  and  to  the  nutrition  of 
the  muscles,  and  it  has  been  shown  by  S.  Weir  Mitchell  that  general 
faradization  may  temporarily  elevate  the  general  bodily  temperature.  In 
these  cases  the  current  produces  wide-spread  muscular  contractions,  and  it 
is  doubtful  how  far  these  are  the  cause  of  the  quickening  of  the  circulation 
and  how  far  the  arterioles  are  directly  affected  by  the  electricity  ;  it  may 
also  be  that  nutritive  cell  movements  through  the  body  are  quickened 
by  the  current. 

Various  methods  have  been  published  by  authorities  for  using  elec- 
tricity as  a  general  stimulant,  but  the  experience  of  many  years  has  led 
us  to  employ  exclusively  the  faradic  current ;  applying  it  first  with  slow 
interruptions  to  the  various  muscles  and  groups  of  muscles  throughout  the 
body  in  regular  succession.  The  operator  should  begin  with  one  leg  or 
one  arm,  place  the  electrodes  on  the  motor  points,  and  proceed  system- 
atically. 

In  order  to  get  the  best  results,  the  stance  should  last  from  forty 
minutes  to  an  hour,  and  should  be  divided  into  two  parts.  Thirty  to  forty 
minutes  should  be  occupied  in  the  first  part,  during  which  the  effort  is  to 
bring  into  contraction  almost  every  muscle  in  the  body.  The  current 
used  should  be  a  slowly  interrupted  one,  of  such  strength  as  to  produce 
powerful  contractions.  Beginning  at  one  or  other  of  the  extremities,  and 
bearing  constantly  in  mind  the  position  of  the  motor  points,  the  operator 
should  go  over  the  whole  body,  not  forgetting  the  muscles  of  the  chest, 
back,  and  abdomen.  After  the  muscles  of  the  body  have  been  gone  over 
a  large  electrode  should  be  placed  at  the  nape  of  the  neck  or  high  up  be- 
tween the  shoulders,  and  a  second  in  such  position  that  it  will  come  in 
equal  contact  with  the  two  feet,  and  for  twenty  minutes  a  very  rapidly  in- 
terrupted current,  as  strong  as  the  patient  can  bear  without  suffering, 
should  be  passed  through  the  body.  It  is  entirely  possible  that  such 
current  acts  by  stimulating  to  contraction  the  muscle-fibres  in  the  walls  of 
many  of  the  small  blood-vessels. 

MAGNETISM. 

Various  clinicians  assert  that  they  have  obtained  extraordinary  thera- 
peutic results  from  the  use  of  magnets,  but  in  an  elaborate  investigation 
made  by  F.  Peterson  and  A.  E.  Kennelly  with  magnets  of  enormous 
power  upon  frogs,  dogs,  and  human  beings  it  was  conclusively  shown 
that  magnetism  has  no  demonstrable  effect  upon  the  animal ;  and  it  must 
be  concluded  that  the  therapeutic  effect  of  magnets  is  confined  to  their 
psychical  influence  {New  York  Med.  Journ.,  1892,  vol.  Ivi.)- 

*  A  detailed  discussion  of  the  evidence  upon  this  matter  may  be  found  in  the  tenth 
edition  of  this  book.  It  has  been  omitted  here  as  unnecessary,  and  as  having  long  stood 
practically  unanswered. 


PART     II. 

DRUGS: 

SKETCH     OF    THEIR   NATURAL    HISTORY    AND    PHARMACEU- 
TICAL  PREPARATIONS,    WITH    AN   EXHAUSTIVE   STUDY 
OF   THEIR    PHYSIOLOGICAL,    THERAPEUTICAL, 
AND    TOXICOLOGICAL  ACTIONS. 


PRELIMINARY    CONSIDERATIONS. 

ALTHOUGH  PHARMACY,  or  the  science  of  preparing  medicines,  is  en- 
tirely distinct  from  THERAPEUTICS,  or  the  science  of  the  application  of 
medicines  to  the  cure  of  disease,  it  is  evident  that  some  acquaintance  with 
the  former  is  necessary  to  the  correct  appreciation  of  the  latter.  Further, 
the  basis  of  each  of  these  studies  is  a  knowledge  of  MATERIA  MEDICA, 
or  the  substances  used  as  medicines.  PHARMACODYNAMICS  is  the  study 
of  the  effects  of  drugs  on  the  healthy  animal  organism,  that  is  their  physi- 
ological action.  PHARMACOLOGY  is  the  general  term  employed  to  em- 
brace these  three  divisions. 

In  every  civilized  country  there  is  some  recognized  official  list  of  drugs 
and  their  preparations,  known  as  the  Pharmacopoeia.  In  most  places, 
this,  being  prepared  with  the  sanction  of  the  government,  partakes  of  the 
nature  of  a  law,  but  in  the  United  States  conformity  to  it  depends,  at  least 
in  some  States,  merely  upon  the  voluntary  action  of  the  professions  of 
Medicine  and  Pharmacy,  by  a  representative  convention  of  which  it  was 
originally  prepared  and  is  decennially  revised. 

The  preparations  made  from  crude  drugs  are  as  follows  : 

DECOCTA. — Decoctions  are  made  by  boiling  crude  drugs  for  a  greater 
or  less  time  in  water.  It  is  evident  that  this  method  of  preparing  is  ineli- 
gible when  the  active  principle  is  volatile  or  is  easily  decomposed  by  heat, 
or  when  the  drug  contains  much  starch,  whose  extraction  would  make  the 
preparation  very  thick  and  predispose  it  to  rapid  decomposition,  but  is 
well  adapted  to  hard,  woody  substances,  and  to  those  containing  much 
albumin,  which  is  coagulated  by  the  boiling  water  and  not  extracted. 
60 


PRELIMINARY   CONSIDERATIONS.  61 

INFUSA. — Infusions  are  made  with  water,  either  cold  or  hot,  without 
boiling.  They  are  prepared  by  maceration  or  by  displacement. 

LIQUORES. — Solutions  are  preparations  in  which  an  active,  non-volatile 
principle  is  dissolved  in  water. 

AQU^E. —  Waters  are  solutions  of  volatile  principles  in  water. 

MISTUR.E. — Mixtiires  are  preparations  in  which  one  or  more  me- 
dicinal substances  are  held  in  suspension  in  water.  Of  such  nature  are 
EMULSI,  (emulsions'}  in  which  some  oily  material  is  suspended  by  a 
gummy  or  an  albuminous  body. 

MUCILAGINES. — Mucilages  are  solutions  of  gummy  substances  in 
water. 

SYRUPI. — Syrups  are  sugary  liquids,  the  menstruum  or  basis  of  which 
is  water,  with,  in  some  cases,  vinegar  or  alcohol. 

MELLITA. — Honeys  are  preparations  whose  basis  is  honey. 

ACETA. —  Vinegars  are  preparations  in  which  vinegar  or  dilute  acetic 
acid  is  used  as  the  menstruum. 

TINCTURE. — Tinctures  are  alcoholic  solutions  prepared  by  maceration 
or  displacement  from  the  crude  drug,  or  by  dissolving  non-volatile  princi- 
ples. In  some  of  them  strong,  in  others  dilute,  alcohol  is  used. 

SPIRITUS. — Spirits  are  alcoholic  solutions  of  volatile  principles,  made 
by  direct  solution  or  by  distillation  from  the  crude  drugs. 

VINA. —  Wines  are  preparations  whose  menstruum  is  wine. 

GLYCERITA.  —  Glycerites  are  preparations  in  which  glycerin  is  the 
solvent. 

OLEA  DESTILLATA. —  Volatile,  distilled,  or  ethereal  oils  are  active  prin- 
ciples obtained  from  plants  by  distillation  or  by  other  processes.  They 
have  no  chemical  relations  with  fixed  oils,  and  are  readily  to  be  distin- 
guished by  the  fact  that  the  stain  which  they  leave  upon  paper  disappears 
in  a  little  time.  They  are  usually  composed  either  of  carbon  and  hydro- 
gen, or  of  carbon,  hydrogen,  and  oxygen,  to  which,  in  the  case  of  certain 
bad-smelling  oils,  sulphur  is  added.  By  oxidation  they  are  converted 
into  resinous  compounds.  They  are  all  inflammable,  usually  of  powerful 
odor,  commonly,  but  not  in  all  instances,  lighter  than  water,  slightly 
soluble  in  water,  and  freely  soluble  in  petroleum  benzin.  By  the  destruc- 
tive distillation  of  various  organic  substances  are  obtained  products  resem- 
bling somewhat  volatile  oils.  These  are  the  so-called  empyreumatic  oils. 

OLE  ATA. — Oleates  are  solutions  of  definite  principles  in  oleic  acid. 

OLEORESIN^E. — Oleoresins  are  concentrated  preparations  composed 
generally  of  a  volatile  oil  and  a  resin.  They  are  really  ethereal  extracts, 
made  by  the  action  of  ether  upon  the  crude  drugs  ;  in  the  case  of  ginger, 
a  mixture  of  alcohol  and  ether  is  used. 

Succi. — Fresh  juices  are  obtained  by  expression  of  the  green  plant, 
enough  alcohol  being  added  to  preserve  them. 

EXTRACTA. — Extracts  are  solid  preparations  made  in  various  ways 
from  the  crude  drug.  They  are  of  a  consistency  suitable  for  the  prepara- 
tion of  pills. 


62  PRELIMINARY   CONSIDERATIONS. 

FLUIDEXTRACTA. — Fluidextracts  are  fluid  preparations  so  made  that 
one  minim  represents  one  grain  of  the  crude  drug. 

RESIN^E. — Resins  are  peculiar  solid  vegetable  active  principles,  soluble 
in  alcohol  and  insoluble  in  water,  most  of  which  are  obtained  by  the  pre- 
cipitation of  saturated  tinctures  with  water.  The  majority  of  the  official 
resins  are  purgatives. 

CONFECTIONES. — Confections  are  medicinal  substances  beaten  up  with 
sugar  into  a  pasty  mass. 

TROCHISCI. —  Troches,  or  lozenges,  are  gummy  pellets  or  disks,  so 
made  as  to  dissolve  slowly  in  the  mouth. 

SUPPOSITORIA. — Suppositories  are  conical  bodies,  prepared  for  intro- 
duction into  the  rectum,  where  they  melt  with  the  heat  of  the  body. 
Their  basis  is  generally  cacao  butter. 

UNGUENTA  and  CERATA. — Ointments  and  Cerates  are  fatty  solid 
preparations  for  external  use.  The  cerates  containing  wax  (cera)  are  the 
firmer  of  the  two. 

EMPLASTRA. — Plasters  are  solid  substances  spread  by  the  aid  of  heat 
upon  muslin,  skin,  or  other  similar  material,  and  of  such  nature  as  to  be 
adhesive  at  the  temperature  of  the  body. 

CHARTS.  — Papers  are  medicated  leaves  or  sheets  of  paper  for  exter- 
nal use.  The  only  official  papers  are  those  of  mustard. 

LINIMENTA. — Liniments  are  liquid  preparations,  for  external  use. 
The  names  PILUL^E  (Pills')  and  PULVERES  (Powders)  sufficiently  in- 
dicate the  character  of  the  preparations. 

The  effects  of  medicine  are  commonly  divided  into  the  direct  and  in- 
direct. An  example  will  probably  show  the  difference  between  these  in 
the  briefest  and  most  forcible  manner.  Thus,  the  direct  effect  of  a  diuretic 
is  increased  urination  ;  the  indirect  effect  may  be  removal  of  serous 
effusion  in  some  part  of  the  body  which  is  brought  about  not  by  the  medi- 
cine itself,  but  by  the  changes  it  induces  ;  the  increased  excretion  caus- 
ing a  diminution  of  the  amount  of  the  fluid  in  the  blood-vessels,  which  in 
turn  leads  to  absorption.  The  term  local  action  indicates  the  effects  of 
drugs  upon  that  part  of  the  body  with  which  they  first  come  in  contact, 
as  the  stomach  ;  by  general  action  is  understood  their  effects  on  distant 
parts  of  the  body  to  which  they  are  carried  by  the  blood  after  being 
absorbed. 

The  term  or  expression  indication  for  a  given  remedy,  being  in  constant 
use,  ought  to  be  distinctly  understood  ;  by  it  is  meant  the  pointings  of 
nature,  or,  in  other  words,  the  evident  needs  of  the  system.  Thus,  hard 
faeces  collected  in  the  colon  are  an  indication  for  a  purgative  of  such  char- 
acter as  will  produce  watery  secretions  to  soften  them.  Relaxation  in  a 
part  indicates  a  remedy  that  will  awaken  into  new  life  the  natural  contrac- 
tility of  the  part, — i.e. ,  an  astringent.  Again,  the  suppression  of  secre- 
tion from  over-excitement,  or  from  irritation,  is  an  indication  for  some 
drug  which  will  allay  irritation  ;  while  the  same  suppression,  when  depend- 
ent upon  torpor  or  loss  of  cell-activity,  will  call  for  an  excitant, — an  irri- 


PRELIMINARY   CONSIDERATIONS.  63 

tant.  The  childish  absurdity  of  treating  symptoms  by  any  such  law  as 
"similia  similibus  curantur"  or  "  dissimilia  dissimilibus  curantur"  is  at 
once  apparent.  The  same  symptoms  may  be  the  result  of  absolutely 
antagonistic  conditions  and  require  absolutely  opposite  treatment.  With- 
out occupying  space  with  details,  one  example  will  suffice.  Either  irrita- 
tion or  depression  of  the  stomach  may  cause  vomiting.  Therefore  in  one 
case  of  vomiting  a  stomachic  stimulant  such  as  ipecacuanha,  which  when 
given  freely  in  health  will  produce  vomiting,  may  relieve  the  nausea  be- 
cause the  depressed  stomach  needs  a  stimulation  to  bring  it  to  the  normal 
level  ;  in  another  case  a  stomach  which  rejects  food  because  it  is  irritated 
needs  a  sedative  like  bismuth,  which  in  health  will  not  produce  vomiting. 
In  the  first  case  the  law  of  similars  seems  to  hold  good,  in  the  second  the 
law  of  dissimilars  appears  to  be  dominant.  A  law  of  nature  has  no  excep- 
tions. If  an  alleged  law  of  nature  has  exceptions  it  is  not  a  law.  If  it 
were  proved  that  under  certain  circumstances  the  earth  without  the  inter- 
vention of  any  second  force  repels  bodies,  we  should  know  that  the  alleged 
law  of  gravity  is  not  a  law.  It  is  plain,  therefore,  that  neither  of  the 
alleged  therapeutic  laws  of  similars  or  of  dissimilars  is,  in  truth,  a  law. 
They  are  the  results  of  coincidence,  the  expressions  of  half  truths. 
Symptoms  are,  indeed,  but  the  surface-play  of  disease,  and  the  rational 
therapeutist  always  seeks  their  hidden  meaning.  The  conscientious 
physician  refuses  to  practise  upon  homoeopathic,  allopathic,  or  any  other 
restricted  basis,  but  gleans  therapeutic  knowledge  from  all  sources,  guiding 
himself  as  far  as  may  be  by  the  light  of  reason  and  science,  but  hesitating 
not  to  go  beyond  into  the  region  of  the  unknown  and  uncertain  when 
distinctly  led  by  the  lantern  of  empiricism. 

By  far  the  greater  number  of  remedies  are  absorbed  into  the  blood, 
and  thus  find  access  to  the  part  upon  which  they  act.  It  is  necessary, 
therefore,  for  them  to  be  so  placed  that  they  can  be  taken  into  the  blood- 
vessels. 

There  are  five  paths  of  entrance  for  medicines  into  the  circulation, — 
the  stomach,  the  cellular  tissue,  the  rectum,  the  skin,  and  the  lungs.  By 
far  the  most  frequently  employed  of  these  is  the  stomach.  It  is  evident 
that,  in  order  to  pass  rapidly  and  readily  into  the  absorbents,  medicines 
must  be  in  solution.  When  administered  by  the  stomach,  however,  it  is 
equally  plain  that  solubility  in  an  ordinary  menstruum,  such  as  water,  is 
not  a  sine  qua  non,  since  the  varying  acidities,  alkalinities,  and  organic 
contents  of  the  alimentary  juices  give  to  them  a  solvent  power  far  above 
that  of  less  complex  and  varying  fluids.  Thus,  a  medicine  insoluble  in 
water  may  be  dissolved  by  the  acids  of  the  gastric  juice,  while  another 
drug  may  owe  its  activity  to  its  solution  by  the  alkalies  or  by  the  fatty 
matters  of  the  intestinal  fluids. 

The  dissolving  power  of  the  rectal  fluids  is  very  slight :  hence,  in  order 
to  act  efficiently,  medicines  when  given  by  the  rectum  must  be  in  solution 
or  be  readily  soluble.  Absorption,  moreover,  does  not  occur  so  rapidly 
from  the  rectum  as  from  the  upper  bowel,  and  a  longer  time  is  therefore 


64  PRELIMINARY   CONSIDERATIONS. 

needed  to  impress  the  system  in  this  way.  In  the  great  majority  of  cases 
medicines  are  thus  exhibited  to  obtain  peculiar  effects  more  or  less  local 
in  character.  Thus,  an  opium  suppository  is  given  in  dysentery,  or  to 
quiet  irritation  of  the  genito-urinary  organs. 

Medicines  which  are  thrown  into  the  subcutaneous  tissue  are  said  to  be 
administered  hypodermically.  The  syringe  employed  is  provided  with  a 
sharp  needle,  which  must  be  kept  scrupulously  clean  and  free  from  rust. 
The  medicine  must  be  in  perfect  solution  and  not  too  irritating.  The 
advantages  of  this  method  of  exhibition  are  promptness  and  certainty  of 
action.  If  twenty  minutes  be  required  for  the  absorption  of  a  certain 
medicine  from  the  stomach,  forty  minutes  will  be  usually  necessary  when 
it  is  exhibited  by  the  rectum,  and  five  minutes  when  it  is  thrown  into  the 
subcutaneous  tissue.  The  objections  to  the  hypodermic  method  are,  first, 
the  danger  of  producing  local  inflammation  and  abscesses  ;  second,  the 
possibility  of  throwing  the  whole  mass  directly  into  a  vein  and  having  it 
swept  in  concentrated  form  into  the  heart  or  nerve-centres.  We  have  seen 
the  injection  of  a  sixth  of  a  grain  of  morphine  followed  inside  of  a  minute 
by  complete  unconsciousness,  collapse,  arrest  of  respiration,  dropping  of 
the  jaw,  and  apparent  death.  The  danger  of  such  a  mischance  can  be 
greatly  lessened  by  withdrawing  the  point  of  the  needle  an  eighth  of  an 
inch,  after  it  has  been  plunged  into  the  tissue.  The  local  irritation  occa- 
sioned by  hypodermic  injections  has  not  only  very  frequently  produced 
abscesses,  but  in  not  a  few  cases  has  caused  fatal  tetanus.  Excessive 
irritation  can  be  largely  prevented  by  certain  precautions,  but  there  are 
many  medicinal  substances  whose  hypodermic  employment  might  be  ad- 
vantageous were  they  not  too  irritant  for  such  use.  In  all  cases  solution 
must  be  complete,  and  if  the  medicinal  substance  be  of  such  nature  that 
it  is  liable  to  be  precipitated  by  alkalies,  an  excess  of  acid  should  be  pres- 
ent in  the  water  to  prevent  precipitation  by  the  juices  of  the  cellular  tissue. 
An  irritant  which  is  rapidly  taken  up  from  the  part  may  produce  at  first 
smarting  and  pain  without  creating  any  permanent  irritation,  but  a  small 
solid  particle  lying  in  the  cellular  tissue  is  almost  sure  to  cause  inflamma- 
tion and  abscess.  All  hypodermic  injections  should,  therefore,  be  filtered 
before  being  used.  It  is  of  the  utmost  importance,  even  when  a  non- 
irritating  substance  is  employed,  that  the  injection  should  be  absolutely 
aseptic.  No  solution  which  has  undergone  any  decomposition  or  con- 
tains any  growth  should  be  used.  Ordinarily  the  solution  should  be 
freshly  made  with  boiled  water.  When  hypodermic  solutions  are  in- 
tended to  be  kept,  they  should  contain  five  per  cent,  of  carbolic  acid 
with  a  drop  or  two  of  glycerin  to  every  fifteen  minims,  which  is  the 
maximum  amount  that  should  be  injected  at  one  time.  A  considerable 
proportion  of  glycerin  will  throw  out  of  solution  most  of  the  alkaloids,  but 
when  solution  of  the  medicinal  substance  is  distinctly  favored  by  glycerin, 
as  is  the  case  with  extracts,  three  or  four  drops  of  the  glycerin  should  be 
added  to  the  hypodermic  solution.  If  the  injection  be  thrown  directly 
under  the  skin,  it  may,  by  raising  and  tearing  the  skin  from  its  attach- 


PRELIMINARY   CONSIDERATIONS.  65 

merit,  so  interfere  with  the  supply  of  blood  as  to  cause  local  irritation. 
The  liquid  should,  therefore,  always  be  thrown  deeply  into  the  tissues, 
where  it  may  diffuse  itself. 

There  are  several  ways  in  which  medicinal  principles  are  introduced 
through  the  skin,  although  the  only  one  in  common  use  is  the  application 
of  medicated  fatty  preparations,  either  with  or  without  friction.  Absorp- 
tion takes  place,  of  course,  most  rapidly  at  those  places  where  the  skin  is 
thinnest, — the  inside  of  the  thighs,  the  surface  of  the  abdomen,  and  espe- 
cially the  armpits.  Absorption  will  take  place  through  the  skin  from 
baths  so  slowly  that  medicated  baths  are  rarely  used,  except  for  their 
local  influence  on  the  skin.  Formerly,  medicines  were  sometimes  ex- 
hibited by  placing  them  on  blistered  surfaces,  beneath  the  raised  cuticle  ; 
at  present  this  endermic  method  is  very  rarely  employed. 

In  order  for  a  medicine  to  be  absorbed  through  the  lungs  it  must  be 
vaporizable  at  the  body  temperature,  and  not  too  irritant  to  be  inhaled. 

For  local  purposes  medicines  are  applied  to  various  parts, — to  the 
skin,  ear,  nares,  fauces,  stomach,  larynx,  lungs,  rectum,  vagina,  urethra, 
etc.  For  the  last  three,  liquid  preparations  known  as  injections,  or  solid 
ones  known  as  suppositories,  or,  in  case  of  the  urethra,  as  bougies,  or 
sometimes  as  urethral  suppositories,  are  employed. 

For  the  purpose  of  making  local  applications  to  the  respiratory  organs, 
atomization  is  very  commonly  practised.  Many  forms  of  apparatus  are  in 
use,  but  the  principle  in  all  of  them  is  the  same.  A  rapid  current  of  air, 
or  of  steam,  is  forcibly  ejected  from  a  horizontal  pipe,  through  a  capillary 
orifice,  directly  across  a  similar  opening  in  a  vertical  tube.  The  rush  of 
the  vapor  over  this  second  orifice  forms  a  vacuum  ;  the  fluid  into  which 
the  base  of  the  vertical  tube  is  set,  rushing  up  to  fill  this,  is  sucked  or 
drawn  out  through  the  orifice,  and  as  it  emerges  is  broken  into  a  fine 
spray,  and  is  carried  along  by  the  current  of  air  or  steam  into  a  mouth- 
piece, at  which  sits  the  patient.  It  cannot  be  gainsaid  that  in  this  way 
we  are  able  to  carry  medicinal  substances  not  merely  into  the  larynx,  but 
into  the  lungs  themselves.  Volatile  medicines  vaporized  by  heat  are  also 
sometimes  employed  in  the  treatment  of  lung  affections. 

There  are  various  classes  of  agencies  which  so  modify  the  action  of 
drugs  as  to  necessitate  their  consideration.  Such  are  disease,  climate, 
habit,  temperament,  idiosyncrasies,  sex,  age,  time  of  administration,  and 
emotions. 

Disease  often  fortifies  the  system  against  the  action  of  remedies,  so 
that  the  dose  has  to  be  greatly  increased  to  obtain  perceptible  effects. 
Thus,  pain  or  delirium  tremens  will  interfere  greatly  with  the  production 
of  narcotism  by  opium.  Disease  may  altogether  prevent  the  action  of  a 
remedy.  In  all  these  cases  two  rules  should  never  be  lost  sight  of :  first, 
never  give  the  medicine  in  such  doses  as  would  in  health  cause  death  ; 
second,  always  be  sure,  before  giving  large  amounts,  that  the  remedy 
will  not  make  matters  worse  (as  a  drastic  in  intussusception). 

Climate,  by  producing  physical  habits  or  tendencies  in  the  patient, 

5 


66  PRELIMINARY   CONSIDERATIONS. 

often  greatly  influences  the  proper  selection  and  dose  of  remedies.  It  is 
only  necessary  to  allude  to  the  great  consumption  of  quinine  in  malarial 
regions  as  an  example. 

Habit — including  mode  of  life — seems  to  alter,  as  it  were,  the  very 
constitution  of  man.  Not  only  does  it  give  type  to  disease,  by  producing 
habitual  plethora,  or  its  opposite,  but  it  also  fortifies  against  the  action  of 
single  remedies,  or  whole  classes  of  them.  Thus,  in  the  opium-eater,  a 
dose  sufficiently  large  to  kill  an  ordinary  man  serves  only  to  gratify  the 
cravings  of  appetite.  Again,  a  man  accustomed  to  one  narcotic,  as  alco- 
hol or  opium,  loses,  to  a  greater  or  less  degree,  his  susceptibility  to  all 
narcotic  influence  ;  and  the  patient  whose  bowels  require  daily  to  be  moved 
by  a  cathartic  finds  that  he  reacts  more  and  more  slowly  to  medicines  of 
that  class.  Again,  a  nervous  system  blunted  by  exposure  and  toil  in  the 
open  air  is  far  less  susceptible  to  the  action  of  remedies,  and  requires 
larger  doses  to  influence  it,  than  does  the  delicate  organization  of  a  woman 
weakened  by  indolence  and  luxury. 

Temperaments  are  peculiarities  of  organization  characterizing  classes 
of  individuals  ;  idiosyncrasies,  peculiarities  belonging  to  single  individuals. 
This  is  scarcely  the  place  to  discuss  the  subject  of  temperaments,  but  it  is 
allowable  to  state  that  while  the  phlegmatic  person  is  no  more  easily  moved 
by  medicinal  than  by  other  agencies,  the  nervous  individual  answers  as 
quickly  to  the  one  as  to  the  other.  Idiosyncrasies  seem  at  present  to  be 
beyond  law.  They  are  often  very  remarkable,  and  a  knowledge  of  them 
is  most  important  for  the  practitioner.  Thus,  a  relative  of  the  authors'  is 
thrown  into  the  most  alarming  fainting-fits  by  eating  even  so  much  butter 
as  would  be  ordinarily  used  as  a  dressing  for  vegetables  at  dinner.  Some 
persons  are  poisoned  by  the  slightest  touch  of  turpentine,  others  are 
frightfully  salivated  by  a  mere  particle  of  a  mercurial.  These  idiosyncra- 
sies are  numerous,  cannot  be  foreseen,  and  are  often  very  important : 
hence  the  necessity,  in  prescribing  for  an  unfamiliar  patient,  of  always 
asking  as  to  his  or  her  peculiarities. 

Sex  modifies  all  diseases  connected  with  the  organs  or  the  process  of 
generation,  but  it  also  does  more.  Woman  is  more  impressible,  less 
robust,  with  less  power  of  resisting  external  agencies,  than  is  man.  Con- 
sequently, the  dose  for  her  should,  as  a  rule,  be  less  than  that  for  him.  It 
is  needless  to  remark  here  at  length  on  the  necessity  for  abstinence  from 
strongly  perturbing  remedies  during  pregnancy  or  at  menstrual  periods. 

Age,  of  course,  modifies  materially  the  dose.  The  rule  of  Young, 
the  one  which  is  the  most  practical  and  generally  useful,  is  to  add  twelve 
to  the  age  and  divide  the  age  by  the  result.  Thus,  a  child  one  year  old 
would  require  one-thirteenth,  one  three  years  old  three-fifteenths,  of  the 
amount  necessary  for  an  adult.* 

*  Clarke's  rule  (Boston  Med.  and  Surg.Journ.,  1872)  is  too  cumbersome  for  ordinary 
purposes.  It  is  based  upon  relative  weights. 

"  Assuming  the  average  weight  of  an  adult  to  be  one  hundred  and  fifty  pounds,  for 
whom  an  appropriate  dose  is  i,  or  one  drachm,  the  dose  of  most  medicines  must  be  in- 


PRELIMINARY   CONSIDERATIONS.  67 

Purgatives  should  usually  be  given  to  children  in  larger,  narcotics  in 
much  smaller,  doses  than  are  called  for  by  Young's  rule. 

Time  of  Administration, — Absorption  takes  place  most  rapidly  in  an 
empty  stomach,  and  consequently,  when  rapidity  of  action  is  desired,  the 
medicine  should  be  given  under  such  circumstances.  Thus,  a  purgative 
acts  soonest  when  given  before  breakfast.  Substances  which  are  irritating 
to  the  stomach  should  always  be  administered  not  only  properly  diluted, 
but  also  when  the  viscus  is  filled  by  a  mass  of  food,  which  may  serve  still 
further  to  lessen  their  concentration.  Hence  such  remedies  as  iodine  and 
arsenic  are  preferably  exhibited  after  meals.  On  the  other  hand,  when- 
ever a  remedy  is  especially  intended  to  act  on  the  mucous  membrane  of 
the  stomach,  it  should  be  given  when  the  viscus  is  empty.  Again,  some 
drugs,  such  as  iron,  are  best  dissolved  by  the  acid  gastric  juice,  and  it  is 
a  matter  of  some  importance  to  place  them  in  the  stomach  after  eating, 
when  the  process  of  digestion  is  most  vigorous. 

Mental  Emotion. — Space  is  wanting  to  discuss  at  any  length  the  influ- 
ence of  the  imagination  upon  the  action  of  remedies,  and  the  reader  is 
referred  to  the  delightful  book  of  Tuke  for  illustrations.  Suffice  it  to 
state  that  a  positive  announcement  that  a  remedy  will  have  a  certain  effect 
has  often  a  most  remarkable  influence  in  producing  that  effect,  especially 
on  persons  of  nervous  organization  and  of  not  too  great  culture  to  have 
faith.  We  have  given  a  hypodermic  injection  of  a  grain  of  morphine  to  a 
man,  inducing  a  degree  of  hypnotism,  and  the  next  day,  doubling  the  size 
of  the  injection  but  withdrawing  all  morphine,  have  caused  a  much  more 
intense  effect. 

ON  THE  ART  OF  PRESCRIBING  MEDICINES. — In  the  practical  use  of 
remedies,  very  much  depends  upon  the  methods  of  their  combination, 
and,  so  far  as  concerns  the  reputation  of  the  physician,  no  little  impor- 
tance is  to  be  attached  to  the  mere  prescription-writing.  The  recipes  of 
the  master  are  very  widely  seen,  and  he  who  is  incorrect  in  the  grammar 
or  spelling  of  his  English  or  Latin,  or  departs  without  reason  from  the 
traditional  forms,  lays  himself  open  to  ridicule,  than  which  nothing  is 
more  damaging.  A  crooked,  bad  chirography  is  the  traditional  mark  of 
literary  fame  ;  but  absolute  plainness  should  be  a  sine  qu&  non  in  the 
writer  of  prescriptions.  This  should  also  apply  to  abbreviations  :  these 
should  be  of  such  a  character  as  not  only  to  be  readily  made  out,  but  also 
to  be  so  evident  as  to  afford  no  shelter  to  the  apothecary  whose  careless- 
ness has  led  to  serious  error.  In  the  case  of  alkaloids  and  other  powerful 
remedies,  the  chief  name  at  least  should  be  written  in  full.  In  writing 

creased  or  diminished  in  the  proportion  of  the  weight  of  the  patient  to  that  number  of 
pounds.  This  proportion  is  represented  by  a  fraction  whose  numerator  is  the  patient's 
weight  and  whose  denominator  is  150.  If  a  child  at  birth  weighs  six  pounds,  the  appro- 
priate dose  for  it  would  be  Tf0,  or  ^ ;  if  it  weighs  ten  pounds,  1%,  or  A-  A  child  two 
years  old,  weighing  twenty  pounds,  would  require  ^&,  or  about  }  of  an  adult  dose ;  or, 
more  precisely,  7J5.  A  person  whose  weight  is  two  hundred  pounds  should  have  f88>  or 
ih  of  an  average  adult  dose," 


68  PRELIMINARY   CONSIDERATIONS. 

the  prescription,  all  the  ingredients  should  first  be  put  down,  then  the 
number  of  doses  should  be  decided  upon,  and  the  individual  amounts  of 
each  substance  marked  seriatim.  It  is  a  very  good  custom  always  to 
place  first  upon  the  list  the  strongest  of  the  drugs  employed. 

The  art  of  combining  remedies  is  not  a  difficult  one  ;  but  in  practice 
certain  principles  should  not  be  lost  sight  of.  Chief  of  these  are,  to  pre- 
scribe as  few  remedies  as  possible,  and  to  use  no  powerful  drug  without  a 
very  distinct  idea  of  what  it  is  intended  to  do.  Whenever  it  is  desired  to 
give  a  powerful  remedy  in  increasing  doses  until  its  physiological  effect  is 
produced,  it  should  always  be  given  by  itself.  Thus,  it  may  be  necessary 
to  give  arsenic  so  as  to  impress  the  system,  at  the  same  time  that  iron  is 
indicated  ;  but  the  two  remedies  should  be  given  separately,  so  that  the 
dose  of  either  can  be  increased  or  diminished  independently  of  the  other. 

The  principles  of  combination,  formulated  below,  were  long  ago  enun- 
ciated by  Paris,  but  are  to-day  as  imperative  as  ever.  Medicines  are 
combined, — 

First.  To  augment,  correct,  or  modify  the  action  of  a  medicine. 
Thus,  purgatives  act  much  more  kindly  when  a  number  of  them  are 
united  together.  The  chief  reason  of  this  probably  is,  that  as  different 
remedies  affect  different  portions  of  the  gut,  the  whole  intestine  is  best 
reached  by  a  union  of  the  diverse  substances.  It  may  take  an  intense 
irritation  of  the  mucous  membrane  to  purge  as  actively  as  does  a  mild 
irritation  of  both  the  mucous  membrane  and  the  muscular  coat. 

There  are  powerful  medicines  which  act  similarly  upon  some  parts  of 
the  organism,  but  dissimilarly  upon  other  parts.  By  combining  such 
remedies  powerful  effects  can  be  obtained  at  the  points  where  the  two 
lines  of  action  cross  each  other,  without  influencing  to  a  great  extent 
other  portions  of  the  system.  Thus,  chloral  produces  sleep  by  its  action 
upon  the  brain,  and  also  has  a  distinct  influence  upon  the  heart,  but  none 
upon  the  intestinal  tract.  Morphine  acts  upon  the  brain,  and  does  not 
influence  the  heart,  but  has  a  powerful  effect  upon  the  intestinal  tract. 
By  combining  chloral  and  morphine  we  get  an  overwhelming  conjoined 
influence  upon  the  brain  in  producing  sleep  with  the  least  possible  dis- 
turbance of  the  heart  and  of  the  intestinal  tract. 

Secondly.  To  obtain  the  joint  action  of  two  or  more  diverse  remedies. 
Thus,  in  a  cough  mixture,  morphine  may  be  included  to  quiet  the  cough, 
while  ipecacuanha  and  squill  (in  accordance  with  the  first  principle)  are 
added  to  affect  the  mucous  membrane.  The  application  of  this  principle 
requires  caution,  or  the  practitioner  will  be  led  into  that  chief  abomina- 
tion, polypharmacy.  It  is  worse  than  futile  to  attempt  to  prescribe  for 
every  symptom.  It  is  the  underlying  cause  of  the  disorder  or  the  under- 
stratum of  bodily  condition  which  must  be  sought  out  and  prescribed  for 
simply. 

Thirdly.  To  obtain  a  special  combination  which  is  really  a  new 
remedy,  or  which  experience  has  shown  acts  almost  as  a  new  remedy. 
Thus,  when  to  potassium  iodide  in  solution  corrosive  sublimate  is  added, 


PRELIMINARY   CONSIDERATIONS.  69 

a  new  chemical  compound  is  formed,  which  experience  has  shown  to 
be  of  great  value  in  syphilitic  diseases.  Griffith's  antihectic  mixture 
is  another  instance  of  the  use  of  chemical  changes,  the  protocarbonate 
of  iron  being  formed  out  of  the  sulphate  of  the  metal  and  the  carbonate 
of  potassium.  In  the  famous  Dover's  powder  no  chemical  change  occurs, 
but  the  ordinary  action  of  opium  upon  the  skin  is  so  enhanced  that  the 
combination  may  be  looked  upon  almost  as  a  new  remedy. 

Fourthly.  To  afford  a  suitable  form.  Thus,  acacia  is  added  to  make 
an  emulsion,  or  confection  of  rose  to  make  a  pill.  In  the  choice  of 
excipients,  care  should  be  exercised  to  select  a  substance  free  from  medi- 
cal properties,  having  no  chemical  incompatibility  with  the  medicinal 
agent,  and  of  suitable  physical  character.  Bread-crumbs  often  make  a 
good  basis  for  pills  ;  but  with  silver  nitrate  they  are  chemically  incom- 
patible, on  account  of  the  chlorides  in  them.  When  writing  a  prescrip- 
tion, the  utmost  care  should  be  taken  to  use  such  excipients  that  the 
combination  shall  not  only  be  attractive  to  the  eye,  but  also  as  little  repul- 
sive to  the  palate  as  may  be.  Whenever  possible,  the  pill  form  should  be 
employed  with  bitter  or  disagreeable  medicines.  The  pill  may  be  readily 
coated  with  silver-foil  ;  tonic  pills  may  be  coated  with  iron  by  shaking  or 
rolling  them  in  ferri  pulvis  while  soft  and  sticky.  Sugar-coated  pills  and 
"  compressed  pills"  are  liable  to  get  so  hard  and  insoluble  that  their  use 
requires  caution.  In  regard  to  mixtures,  flavoring  oils  should  be  freely 
used,  and  the  power  of  glycerin  to  conceal  the  disagreeable  taste  of  many 
substances  should  be  remembered.  Whenever  practicable,  nauseous 
medicines  should  be  given  in  capsules.  These  occur  in  two  forms.  Hard 
capsules  are  prepared  to  be  filled  extemporaneously.  They  can  be  made 
large  enough  to  hold  ten  minims,  although  this  size  cannot  be  easily  swal- 
lowed by  every  person  without  a  little  training.  The  soft,  flexible  cap- 
sules are  filled  by  the  manufacturing  chemists.  They  can  be  readily 
swallowed  by  most  persons  up  to  the  size  of  one  drachm.  Not  only  may 
solid  preparations  be  given  in  capsules,  but  also  essential  oils,  volatile 
liquids,  fixed  oils,  and  fluid  extracts  ;  indeed,  almost  any  liquid  the  dose 
of  which  is  not  too  large. 

Incompatibilities. — In  combining  remedies,  the  subject  of  incompati- 
bilities must  never  be  lost  sight  of.  The  kinds  of  incompatibilities  are 
two  in  number, — physiological  and  chemical.  The  first  of  these  it  would 
require  large  space  to  discuss  fully,  and  any  one  familiar  with  the  text  of 
the  book,  if  possessed  of  the  slightest  reasoning  powers,  can  readily  make 
all  necessary  deductions. 

In  many  works  on  materia  medica  long  lists  of  chemical  incompati- 
bilities are  given  in  the  accounts  of  individual  drugs.  These  lists  have 
seemed  to  us  useless,  as  we  have  never  met  with  a  student  who  could  com- 
mit and  retain  them.  Moreover,  they  contain  so  much  matter  of  no 
practical  use  that  the  valuable  portion  is  hidden  from  sight.  A  certain 
amount  of  chemical  knowledge  is  essential  to  the  student,  and  is  not  to  be 
taught  in  a  book  like  the  present.  He  who  would  ignorantly  combine 


70  PRELIMINARY   CONSIDERATIONS. 

sulphuric  acid  and  a  carbonate  needs  to  restudy  his  chemical  text-book. 
All  that  we  shall  do  here  is  to  point  out  certain  principles  and  a  few  especial 
reactions.  The  following  rules  may  serve  for  a  guide  : 

Soluble  salts  which  can  by  mutual  decomposition  form  an  insoluble 
compound  will  undergo  such  decomposition  when  they  meet  in  solution, 
and  will  precipitate,  unless  in  some  very  rare  instances,  in  which  a  double 
salt  is  formed. 

Soluble  salts  which  are  not  capable  of  forming  an  insoluble  salt  never 
precipitate,  and  rarely  undergo  decomposition,  when  they  meet  in  solu- 
tion. 

Mineral  acids  decompose  salts  of  the  weaker  (carbonic,  acetic,  etc.) 
acids,  and  form  ethers  with  alcohol  and  alcoholic  preparations. 

Alkalies  precipitate  the  alkaloids  and  the  soluble  non-alkaline  metallic 
salts. 

Glucosides,  such  as  santonin  and  colocynthin,  should  not  be  prescribed 
with  free  acids  or  emulsin. 

Tannic  acid  and  all  substances  containing  it  are  incompatible  with 
alkaloids  and  glucosides  and  drugs  containing  them,  with  albumin  and 
gelatin,  with  most  soluble  metallic  salts  used  in  medicines. 

Iodine  and  iodides  are  incompatible  with  the  alkaloids  and  the  sub- 
stances containing  them,  as  well  as  with  most  soluble  metallic  salts.  The 
potassium  iodide  *  should  always  be  prescribed  alone,  or  only  in  com- 
bination with  corrosive  sublimate  (with  which  it  forms  a  double  salt),  or 
with  iodine  itself. 

Tinctures  and  other  alcoholic  preparations  containing  resin  precipitate 
the  latter  when  water  is  added. 

Silver  nitrate  should  always  be  prescribed  alone,  or  in  combination 
with  opium  or  extract  of  hyoscyamus  only.  Most  vegetable  extracts  de- 
compose it,  and  with  creosote  it  is  said  to  make  an  explosive  compound. 

Corrosive  sublimate  is  incompatible  with  almost  everything,  and  should 
be  given  in  simple  syrup  :  even  the  compound  syrup  of  sarsaparilla  is  said 
to  decompose  it. 

Syrup  of  squill,  containing  acetic  acid,  is  incompatible  with  ammonium 
carbonate,  but  not  with  the  chloride. 

Lead  acetate  and  subacetate  are  incompatible  with  almost  everything, 
but  are  nevertheless  frequently  used  in  lotion  with  opium,  the  insoluble 
compound  formed  being  therapeutically  active. 

Vegetable  infusions  are  generally  incompatible  with  metallic  salts. 

CLASSIFICATION. — This  book  has  been  arranged  in  accordance  with 
the  scheme  directly  hereafter  set  forth.  Some  of  the  families  as  here 
defined  are  not  thoroughly  natural,  but  most  of  the  groups  have  much  of 
unity  in  themselves  and  of  propriety  in  their  relations.  Thus,  antispas- 

*  Death  has  resulted  from  a  prescription  containing  strychnine  and  potassium  iodide, 
all  the  alkaloid  being  taken  at  the  last  dose. 


PRELIMINARY   CONSIDERATIONS.  71 

modics  are  little  better  than  a  heap  of  incongruities,  but  delirifacients  are 
singularly  united  together  and  opposed  to  somnifacients,  while  anti- 
periodics,  perhaps,  ought  to  be  merged  in  the  alteratives,  with  which 
through  arsenic  they  are  closely  related. 

DIVISION  I. — SYSTEMIC  REMEDIES,  substances  which  act  on  the 
solid  or  fluid  tissues  of  the  body. 

DIVISION  II. — EXTRANEOUS  REMEDIES,  substances  which  are  em- 
ployed to  act  on  secretions,  excretions,  or  other  liquid  or  solid  bodies 
which  are  not  human  tissues. 

SYSTEMIC   REMEDIES. 

CLASS  I. — GENERAL  REMEDIES,  drugs  which  affect  the  tissues  of  the 
body  generally  or  such  organized  systems  as  reach  all  portions  of  the 
body. 

ORDER  I. — Nervines,  drugs  which  affect  the  nervous  system. 

ORDER  II. — Cardiants,  drugs  which  affect  the  circulation. 

ORDER  III. — Nutriants,  drugs  which  affect  the  nutritive  movements 

of  the  body. 

NERVINES. 

A.  Medicines  which  act  on  the  cerebrum. 

B.  Medicines  which  act  on  the  lower  or  neuro-muscular  apparatus. 

A. 

FAMILY  I. — Antispasmodics,  feeble  cerebral  stimulants  which  are  em- 
ployed for  the  relief  of  minor  spasms  and  other  nervous  symptoms,  the 
result  of  insufficient  nerve-power. 

FAMILY  II. — Anesthetics,  drugs  which  are  used  for  the  production  of 
anaesthesia. 

FAMILY  III. — Somnifacients,  drugs  which  when  in  sufficient  doses 
produce  deep  sleep  without  delirium. 

FAMILY  IV. — Delirifacients,  drugs  which  when  in  sufficient  doses 
produce  delirium,  followed  by  stupor. 

B. 

FAMILY  V. — Excito-motors,  drugs  which  produce  violent  tetanic 
spasms. 

FAMILY  VI. — Depresso-motors,  drugs  which  cause  paralysis. 

CARDIANTS. 

FAMILY  I. — Cardiac  Stimulants,  drugs  which  increase  the  arterial 
pressure. 

FAMILY  II. — Cardiac  Depressants,  drugs  which  lower  the  arterial 

pressure. 

NUTRIANTS. 

FAMILY  I.— Astringents,  drugs  which  call  into  exercise  the  vital  func- 
tion of  contractility. 


72  PRELIMINARY   CONSIDERATIONS. 

FAMILY  II.  —  Tonics,  drugs  which  so  influence  nutrition  as  to  increase 
the  reconstruction  or  upbuilding  of  the  tissue  or  tissues  concerned. 

FAMILY  III. — Alteratives,  drugs  which  so  modify  nutrition  as  to  over- 
come certain  chronic  pathological  processes. 

FAMILY  IV. — Antiperiodics,  drugs  which  so  modify  nutrition  as  to 
overcome  the  effects  of  malarial  poisoning. 

FAMILY  V. — Antipyretics,  drugs  which  so  modify  nutrition  as  to  over- 
come febrile  movements. 

CLASS  II. — LOCAL  REMEDIES,  drugs  which  affect  one  organ  or  appa- 
ratus more  or  less  isolated  from  the  remainder  of  the  body. 

FAMILY       I. — Stomachics*  FAMILY  VIII. — Oxytocics. 

II.—  Emetics.  "  IX.— Irritants. 

III.— Cathartics.  "  X.—Escharotics. 

_ ' '         IV.  — Diuretics.  X I .  — Demulcents. 

V.—  Diaphoretics.  "  XII.—  Emollients. 

"         Ml.— Expectorants.  "  XIII.— Protective*. 
"       VII. — Emmenagogucs. 

EXTRANEOUS   REMEDIES. 

FAMILY      I. — Antacids.  FAMILY  IV. — Absorbents. 

"         II. — Anthelmintics.  "         V. — Disinfectants. 

lll.—Digestants. 

*  The  definitions  are  not  given  in  these  families,  as  they  are  old  and  well  known  and 
their  names  show  the  reader  to  what  organs  each  applies.  It  should  be  stated,  however, 
that  the  family  stomachics  contains  drugs  which  are  used  simply  as  stimulants  to  the 
gastro-intestinal  tract,  including,  therefore,  Simple  Bitters,  so  called,  and  Arematics. 


DIVISION    I.— SYSTEMIC    REMEDIES. 

CLASS   I.— GENERAL   REMEDIES. 

ORDER    I.— NERVINES. 


FAMILY   I.— ANTISPASMODICS. 

UNDER  the  name  of  Antispasmodics  are  grouped  in  this  treatise  a 
number  of  medicines  generally  of  very  feeble  powers,  but  of  frequent  use. 
In  certain  conditions  of  the  nervous  system — conditions  associated  with 
weakness  rather  than  with  simple  depression — the  nerve-centres  appear  to 
be  more  susceptible  than  is  normal  to  external  impressions,  as  well  as  to 
those  impulses  which  originate  in  the  cerebral  centres  themselves  and  are 
connected  with  the  emotions.  As  a  result  of  this  state,  various  symptoms 
arise,  of  trifling  import,  but  often  apparently  severe,  and  always  annoying. 
Such  symptoms,  in  their  mildest  form,  constitute  the  state  of  unrest  known 
as  nervousness  ;  in  their  severer  type  they  may  rise  in  intensity  up  to  the 
wildest  convulsion  of  hysteria.  It  is  in  this  class  of  affections  that  the  so- 
called  antispasmodics  are  useful.  As  the  condition  which  they  relieve  is 
always  associated  with  weakness,  they  are  often  spoken  of  as  "  nerve- 
stimulants."  In  regard  to  most  of  them  there  is  but  little  evidence  of 
their  increasing  power  or  functional  activity  when  administered  to  healthy 
individuals.  Some  of  them  act  slightly  upon  the  circulation  when  given 
in  very  large  doses,  and  a  few  when  administered  as  freely  as  possible  in- 
duce slight  cerebral  symptoms,  such  as  vertigo  ;  but,  except  camphor  and 
Hoffmann's  anodyne,  none  are  capable  of  producing  serious  poisoning. 
As  any  theory  of  the  method  in  which  the  hysterical  convulsion  originates 
— of  its  immediate  causes  and  the  mechanism  of  its  production — would, 
with  our  present  knowledge,  be  at  best  but  an  ingenious  speculation,  the 
safest  plan  in  regard  to  the  action  of  drugs  belonging  to  the  class  now 
under  consideration  is  to  accept  the  teachings  of  clinical  experience  as  to 
facts,  and  to  avoid  theorizing  as  to  the  way  in  which  the  results  are  brought 

about. 

MOSCHUS— MUSK.     U.  S. 

A  highly  odorous,  unctuous  substance,  obtained  from  the  glands  situ- 
ated just  in  front  of  the  preputial  orifice  of  the  Moschus  moschiferus,  or 
musk-deer  of  Thibet.  The  genuine  musk-sac  is  to  be  distinguished  from 

73 


74  GENERAL    REMEDIES. 

imitations  of  it  by  the  hairs  being  arranged  concentrically  around  a  minute 
orifice.  As  it  occurs  in  commerce,  musk  is  very  greatly  adulterated. 

PHYSIOLOGICAL  ACTION. — Musk  appears  to  act  upon  the  nervous 
system  simply  as  a  mild  stimulant  and  antispasmodic.  Jorg  and  Sundelin 
have  experimented  with  it  upon  healthy  men  with  somewhat  contradictory 
results.  According  to  the  first-named  observer,  twenty  grains  of  it  induce 
exhilaration  without  lassitude,  but,  according  to  the  latter  authority,  may 
cause  giddiness,  drowsiness,  and  lassitude.  Both  observers  noted  a  slight 
increase  in  the  frequency  of  the  pulse. 

THERAPEUTICS. — Musk  is  at  present  very  little  used,  but  it  is  strongly 
recommended  by  some  of  the  older  writers  in  various  spasmodic  affec- 
tions, especially  in  hysterical  convulsions.  In  hiccough  it  has  been  con- 
sidered a  specific.  In  our  experience,  in  the  crisis  of  low  fevers  when  the 
symptoms  of  nervous  exhaustion  are  extreme  and  threaten  death,  musk 
is  a  very  valuable  remedy.  Thus,  in  advanced  typhoid  fever  a  condition 
sometimes  develops  in  which  the  pulse  is  exceedingly  feeble,  and  the  tem- 
perature has  a  tendency  to  rise  to  a  great  height,  but  yields  almost  imme- 
diately to  the  use  of  cold,  only,  however,  to  remount  as  soon  as  the  cold 
is  withdrawn.  We  have  seen  musk  at  such  time  control  the  temperature, 
steady  the  pulse,  and  apparently  save  life.  In  other  cases  of  advanced 
fevers  the  powers  of  the  system  entirely  give  out,  and  the  patient  passes 
into  a  condition  of  collapse,  with  subnormal  temperature,  and  mayhap 
coma- vigil  :  this  state  we  have  also  seen  relieved  by  musk.  Originally 
recommended  by  Trousseau  in  the  ataxic  pneumonia  of  drunkards, 
musk  may  be  a  useful  remedy  in  any  forms  of  adynamic  pneumonia  when 
there  is  wild  or  muttering  delirium.  From  ten  to  fifteen  grains  of  musk 
(the  best  attainable)  must  be  given  at  a  dose,  preferably  by  rectal  injection, 
suspended  in  mucilage.  The  effect  of  the  single  dose  lasts  about  six 
hours.  The  dose  of  the  Tincture  of  Musk  (TINCTURA  MOSCHI — five 
per  cent.,  U.  S.)  is  from  one  to  two  fluidrachms  (4-8  C.c. ). 

VALERIANA— VALERIAN.     U.  S. 

The  root  of  the  Valeriana  officinalis,  an  herbaceous  perennial  of 
Europe.  It  consists  of  a  short,  yellowish- white  rhizome,  with  numerous 
fibrous  roots,  of  a  bitter  taste  and  peculiar  odor.  Valerian  depends  for 
its  activity  upon  a  volatile  oil  and  the  valerianic  acid  which  it  contains. 

PHYSIOLOGICAL  PROPERTIES. — The  physiological  action  of  valerian 
is  very  feeble.  The  extraordinary  excitement  which  it  produces  in  cats  is 
probably  due  to  a  suggestive  odor  rather  than  to  any  direct  influence. 
Large  doses  of  valerianic  acid  cause  in  rabbits  some  acceleration  of  the 
pulse  and  respiration,  followed  by  lessened  frequency  of  these  functions 
and  general  lassitude.  Enormous  doses  may  produce  a  fatal  gastro-en- 
teritis.  According  to  Butte,1  the  extract  of  valerian  has  a  pronounced 
effect  in  checking  the  destruction  of  glucose  in  the  blood. 

Upon  man,  very  large  doses  (gii  to  giv)  are  said  to  produce  a  feeling 


ANTISPASMODICS.  75 

of  warmth  in  the  stomach  and  quickening  of  the  pulse,  followed  by  nausea, 
vomiting,  and  colicky  pains. 

THERAPEUTICS. — Valerian  is  useful  in  the  state  of  unrest  familiarly 
known  as  nervousness,  is  much  used  in  the  minor  disturbances  of  hysteria, 
and  has  been  employed,  though  with  little  advantage,  in  mania  a  potu 
and  adynamic  delirium  as  an  adjuvant  to  more  powerful  drugs.  The 
dose  of  the  fluid  extract  (FLUIDEXTRACTUM  VALERIANS,  U.  S. )  is 
one  fluidrachm  (4  C.c.)  ;  of  the  ammoniated  tincture  (TiNCTURA  VALE- 
RIANS AMMONIATA — twenty  per  cent.,  U.  S. ),  one  to  three  fluidrachms  ; 
of  the  simple  tincture  (TINCTURA  VALERIANS — twenty  per  cent,  U.  S.), 
one  to  three  fluidrachms  (4-10  C.c.). 

AMMONII  VALERAS.  U.  S.  —  Ammonium  valerate  or  Ammonium 
valerianate,  a  white  salt  in  quadrangular  plates,  effloresces  in  a  dry  and  deli- 
quesces in  a  moist  atmosphere,  has  the  odor  of  valerianic  acid  and  a  sharp, 
sweetish  taste,  and  is  very  soluble  in  water  and  in  alcohol.  According  to 
W.  E.  Parke,1  it  produces  in  the  frog  convulsions  followed  by  general 
paralysis,  both  the  convulsions  and  the  palsy  being  of  spinal  origin,  and 
also  is  capable  by  local  contact  of  killing  any  of  the  higher  nerve-tissues. 
These  effects  are  probably  due  to  the  ammonia,  and  throw  no  light  upon 
the  therapeutic  action  of  the  drug,  which  is  about  equivalent  to  valerian, 
but  sometimes  has  especial  usefulness  in  nervous  headache.  Dose,  ten 
grains  (o.  65  Gm. ) ,  generally  administered  in  the  form  of  an  elixir. 

VALYL. —  Valerianic  acid  Dimethylamid. — This  is  a  colorless  liquid  with  a  pun- 
gent, acrid  taste,  which  has  been  physiologically  investigated  by  Kionka,s  who  states 
that  it  produces  cerebral  excitement,  attended  with  convulsions,  followed  in  the 
cold-blooded  animals  by  general  paralysis ;  the  convulsions  probably  being  of 
cerebral  origin  since  there  is  no  increased  reflex  activity.  It  is  said  primarily  to 
increase  the  blood-pressure  slightly,  probably  by  contracting  the  blood-vessels, 
but  to  have  little  action  upon  the  heart  or  respiration.  Locally  it  is  somewhat 
irritant,  but  may  be  given  in  a  four  per  cent,  aqueous  solution,  and  has  been  used 
with  success,  in  hysterical  vomiting,  neurasthenia,  hysteria,  and  similar  neuroses. 

Dose,  four  to  fifteen  grains  three  times  a  day,  preferably  administered  with  an 
equal  amount  of  tallow  in  gelatin  capsules. 

VALIDOL. — This  is  a  colorless  liquid,  of  a  mild  pleasant  smell  and  a  slightly 
bitter  taste  ;  said  to  contain  thirty  per  cent,  of  menthol  combined  chemically  with 
seventy  per  cent,  of  valerianic  acid.  It  was  originally  proposed  by  Schwersenski  * 
in  the  treatment  of  pruritis,  gastralgia,  coryza,  and  various  mucous  inflamma- 
tions, and  as  an  antispasmodic,  in  migraine,  neurasthenia,  hysteria,  and  other 
neuroses.  Other  clinicians  have  commented  favorably  upon  the  drug  as  an  anti- 
emetic  and  stomachic.  It  is  stated  to  be  chiefly  eliminated  in  the  urine,  to  which 
it  imparts  a  peculiar  odor.  Dose,  five  to  twenty  drops ;  locally,  a  ten  to  fifteen 
per  cent,  ointment  is  recommended. 

Validolum  camphoratum  is  a  ten  per  cent,  solution  of  camphor  in  validol. 

ASAFCETIDA— ASAFETIDA.     U.  S. 

An  exudation  obtained  by  incising  the  living  root  of  the  Ferula  foe- 
tida,  an  umbelliferous  plant  of  Afghanistan.  It  occurs  mostly  in  ir- 
regular opaque  masses  of  a  dull  yellowish  or  pinkish  brown,  white  when 


76  GENERAL    REMEDIES. 

freshly  broken,  of  a  bitter  acrid  taste  and  a  strong  garlicky  odor.  Asa- 
fetida  is  composed  chiefly  of  gum  and  resin,  but  its  properties  are  in  great 
part  due  to  the  volatile  oil,  of  which  it  contains  from  3.5  to  4.5  per  cent. 

PHYSIOLOGICAL  ACTION. — When  taken  into  the  stomach,  asafetida 
acts  as  a  local  stimulant  and  carminative,  and  on  this  account  is  in  some 
parts  of  the  East  used  as  a  condiment.  The  oil  is  without  doubt  absorbed. 
The  evidence  as  to  its  action  upon  healthy  men  is  both  scanty  and  con- 
tradictory. Thus,  while  M.  Pidoux  took  half  an  ounce  in  a  single  dose 
without  perceptible  effects  other  than  to  render  his  secretions  horribly 
offensive  for  two  days,  Jorg  and  his  disciples  found  that  in  twenty-grain 
doses  it  produced  gastric  uneasiness  and  pain  with  alvine  dejections,  in- 
creased the  pulse-frequency  and  animal  warmth,  quickened  the  respira- 
tion, and  caused  headache,  giddiness,  and  erotic  excitement. 

THERAPEUTICS. — Asafetida  is  the  most  efficient  of  the  antispasmodics, 
and  may  often  advantageously  be  substituted  for  valerian  in  functional 
s^asm,  in  hysteria,  and  in  nervousness.  It  differs  from  valerian  in  having 
a  much  more  decided  action  upon  the  mucous  membranes.  It  is  an 
excellent  carminative,  and  in  the  form  of  injection  is  constantly  used  for 
the  relief  of  tympanites.  It  is  valuable  in  dyspepsia,  with  flatulent  colic 
and  costiveness,  of  the  aged  or  hysterical.  As  a  stimulating  expecto- 
rant and  anti spasmodic,  it  is  useful  in  whooping-cough  and  in  chronic 
bronchial  catarrh,  especially  in  old  people  with  an  asthmatic  tendency. 
In  infantile  convulsions,  in  infantile  colic,  and  in  flatulent  constipation, 
asafetida  enemata  (f^ii  to  f^ss  of  milk)  are  useful  and  harmless. 

DOSE. — Dose  of  the  Pills  of  Asafetida  (PILUL^E  ASAFCETID^,  U.  S. , 
three  grains  each),  two  to  four  ;  of  the  mixture  or  milk  of  asafetida 
(EMULSUM  ASAFCETID^ — four  per  cent,  U.  S. ),  half  to  one  fluidounce 
(15-30  C.  c. ),  or  for  injections,  one  to  eight  fluidounces  (30-2400.0.  : 
of  the  tincture  (TixcTURA  ASAFCETID^E — twenty  per  cent. ,  U.  S. ),  half 
to  one  fluidrachm  (2-4  C.c. ). 

SPIRITUS    .dETHERIS    COMPOSITUS—  COMPOUND    SPIRIT    OF 

ETHER.     U.  S. 

Hoffmanri s  Anodyne  consists  of  325  parts  (by  volume)  of  ether,  650 
parts  of  alcohol,  and  25  parts  of  ethereal  oil.  It  is  a  colorless,  inflam- 
mable liquid,  of  an  aromatic,  ethereal  odor,  and  a  burning,  slightly 
sweetish  taste.  Its  specific  gravity  is  0.815.  SPIRITUS  ^ETHERIS,  U.S. , 
which  contains  no  ethereal  oil,  is  often  improperly  sold  under  the  name  of 
Hoffmann's  anodyne.  It  can  be  distinguished  at  once  by  the  fact  that 
forty  drops  of  the  genuine  preparation  will  render  a  pint  of  water  distinctly 
milky,  whilst  the  simple  spirits  of  ether  has  no  such  effect.  Ethereal  Oil 
(OLEUM  ^THEREUM,  U.  S. )  is  a  transparent,  nearly  colorless,  volatile 
liquid,  of  a  peculiar  aromatic  odor,  and  a  sharp,  bitter  taste.  Its  specific 
gravity  is  0.91.  It  is  heavy  oil  of  wine,  prepared  by  the  action  of  an 
excess  of  sulphuric  acid  on  alcohol,  and  diluted  with  an  equal  part  of 
strong  ether. 


ANTISPASMODICS.  77 

PHYSIOLOGICAL  AND  THERAPEUTIC  ACTION. — H.  A.  Hare  found 
that  the  heavy  oil  of  wine  caused  a  rise,  followed,  if  the  dose  were  large 
enough,  by  a  very  marked  fall  both  of  the  pulse-rate  and  of  the  arterial 
pressure.  As  the  primary  rise  in  the  arterial  pressure  did  not  occur  after 
section  of  the  spinal  cord,  it  must  be,  at  least  in  large  part,  due  to  stimula- 
tion of  the  vaso-motor  centre.  The  fall  of  pressure  is  probably  in  part  the 
outcome  of  a  direct  depressant  action  of  the  drug  upon  the  heart,  since 
that  viscus  finally  suffers  diastolic  arrest  ;  but,  as  in  the  earlier  period  of 
lowered  pressure  the  individual  heart-beats  were  extremely  full  and  strong, 
it  is  probable  that  vaso-motor  paralysis  precedes  cardiac  depression  and 
causes  the  lowered  pressure  by  widening  out  the  blood-paths.  This  vaso- 
motor  palsy  Hare  believes  to  be  chiefly  of  peripheral  origin.  In  his 
studies  upon  frogs,  Hare  failed  to  detect  any  indication  of  an  action  of  the 
oil  upon  the  spinal  cord,  nerves,  or  muscles.  He  found  the  toxic  properties 
of  the  heavy  oil  of  wine  to  be  very  feeble  ;  thirty  cubic  centimetres  given 
by  the  mouth  to  a  small  dog  (weight  twelve  pounds)  failed  to  produce 
marked  symptoms.  It  is  therefore  evident  that  the  small  quantity  of  the 
heavy  oil  of  wine  contained  in  Hoffmann' s  anodyne  can  exert  no  very  pro- 
nounced influence  upon  the  human  system,  and  that  the  effect  of  Hoff- 
mann's anodyne  is  chiefly  that  of  ether  and  alcohol  combined.  Clini- 
cal experience  indicates,  however,  that  Hoffmann's  anodyne  is  more 
calmative  than  the  simple  combination  of  ether  and  alcohol.  It  is  a  very 
efficient  carminative,  and  is  also  a  useful  antispasmodic  in  all  the  disorders 
for  which  such  remedies  are  employed,  especially  when  there  is  a  ten- 
dency to  failure  of  the  circulation  ;  in  valvular  cardiac  disease  it  is  often 
very  effective  in  relieving  mild  heart-pains.  The  dose  is  one  to  two 
fluidrachms  (4-8  C.c. ),  repeated  in  half  an  hour  or  an  hour,  if  required, 
and  given  in  cold  water. 

HUMULUS— HOPS.     U.  S. 

The  strobiles  of  Humulus  Lupulus,  or  the  hop-vine,  cultivated  in  North- 
ern and  Middle  Europe  and  in  the  United  States.  Hops  are  soft,  green- 
ish cones,  one  or  two  inches  in  length,  composed  of  thin,  leaf-like,  imbri- 
cated scales,  having  a  bitter  taste  and  a  heavy  narcotic  odor.  At  the 
bases  of  the  scales  is  a  yellowish  powder,  official  under  the  name  of  /,//- 
pulinum.  Lupiilin  is  in  minute  grains,  and  contains,  according  to  Payen, 
two  per  cent,  of  volatile  oil,  10.30  per  cent,  of  bitter  principle,  and  fifty  to 
fifty-five  per  cent,  of  resin.  Volatile  oil  of  hops  is  yellowish,  and  has  a 
strong  odor  of  the  drug  and  an  acrid  taste.  The  bitter  principle  has 
been  obtained  by  Lermer  in  brilliant  rhombic  columns,  of  an  acid  reac- 
tion. Hops  is  a  bitter  tonic  and  a  very  feeble  narcotic,  which  has  been 
given  to  quiet  nervous  irritability,  and  to  strengthen  digestion  in  neuras- 
thenia, and  even  in  delirium  tremens.  In  abnormal  sexual  excitement  it 
has  been  much  used,  but  is  of  no  value.  Dose  of  the  tincture  (TiNCTURA 
HUMULI,  U.  S. ,  1890),  half  a  fluidounce  to  three  fluidounces  (15-9°  C.c. ) ; 
the  oleoresin  of  Lupulin  (OLEORESINA  LUPULIN.E,  U.  S.),  ten  minims 


78  GENERAL  REMEDIES. 

to  a  fluidrachm  (o.  6-4  C.  c. ) ,  in  capsules  if  desired  ;  the  fluid  extract 
(FLUIDEXTRACTUM  LUPULIN^:,  U.  S.),  half  a  fluidrachm  to  one  flui- 
drachm (2-4  C.  c. ).  A  hop  poultice  is  made  by  moistening  with  hot  water 
the  hops  contained,  alone  or  mixed  with  an  equal  part  of  Indian  meal,  in 
a  gauze  bag  of  the  required  size  and  shape. 

CIMICIFUGA— BLACK    SNAKE-ROOT.     U.S. 

The  root  of  Cimicifuga  racemosa,  an  indigenous  herbaceous  plant, 
growing  abundantly  in  shady  woods,  attaining  a  height  of  six  or  seven 
feet,  and  readily  distinguished  by  its  very  large  multi-compound  leaves 
and  its  long-branched  spikes  of  whitish  polyandrous  flowers,  naked  when 
open.  The  root  consists  of  a  knotted  head,  with  numerous  fine,  brittle 
rootlets  ;  the  odor  is  faint,  and  the  taste  bitterish,  somewhat  astringent 
and  acrid.  The  nature  of  its  active  principle  has  not  been  determined. 
Commercial  Cimicifugin  or  Macrotin  is  an  amorphous  resinous  sub- 
stance. The  tendency  of  the  drug  to  deteriorate  on  keeping  indicates 
the  presence  of  a  volatile  principle. 

PHYSIOLOGICAL  ACTION. — There  have  been  no  cases  of  poisoning  by 
cimicifuga,  but  large  doses  produce  giddiness,  intense  headache,  general 
prostration  (evidences  that  it  has  influence  upon  the  cerebrum),  with  re- 
duction of  the  pulse-force  and  rate,  and  occasionally  vomiting,  but  the 
emetic  action  is  never  violent.  That  the  overdose  of  cimicifuga  has  physi- 
ological activity  is  shown  by  the  experiments  of  Hutchinson,1  who  found 
that  in  frogs  it  acts  as  a  depressant  of  the  sensory  side  of  the  spinal  cord, 
producing  complete  anaesthesia  with  loss  of  reflex  activity  at  a  time  when 
voluntary  movement  is  still  preserved,  the  development  of  the  anaesthesia 
not  being  prevented  by  shutting  off  access  of  the  poison  from  the  periph- 
eral nerves  by  tying  the  arteries  of  the  leg,  and  both  motor  nerves  and 
muscles  being  found  after  death  functionally  active.  Upon  the  circulation 
cimicifuga  acts  as  a  depressant,  producing  in  the  mammal  fall  of  the  arterial 
pressure  and  slowing  of  the  pulse,  and  causing  finally  diastolic  arrest  of 
the  heart.  As  the  slowing  of  the  pulse  is  not  prevented  by  previous  sec- 
tion of  the  vagi,  and  as  the  isolated  frog's  heart  becomes  slow  and  in  a 
little  while  paralyzed  after  direct  contact  with  the  cimicifuga,  it  is  evident 
that  the  drug  acts  as  a  direct  depressant  to  the  heart-muscle  ;  but,  since 
Hutchinson  found  that  asphyxia  is  incapable  of  causing  rise  or  pressure 
while  the  heart  is  still  beating  strongly,  it  is  probable  that  it  not  only  de- 
presses the  heart  but  also  the  arterial  system.  Under  the  influence  of 
the  drug  the  respiration  becomes  slow  and  suffers  final  arrest. 

THERAPEUTICS. — Cimicifuga  was  originally  proposed  by  Young*  in 
1831  as  a  remedy  in  chorea,  and  in  the  simple  chorea  of  childhood  its 
value  is  unquestionable.  It  must  be  given  until  it  produces  physiological 
effects,  and  in  most  cases  the  consentaneous  exhibition  of  iron  and  laxa- 
tives materially  aids  it.  We  have  seen  it  promptly  cure  urticaria  of  ner- 
vous origin  after  complete  failure  of  the  usual  treatment.  In  acute  in- 
flammatory rheumatism,  cimicifuga  has  been  highly  recommended,  but  is 


ANTISPASMODICS.  79 

at  present  very  rarely,  if  ever,  used.     In  chronic  bronchitis  it  is  sometimes 
employed  with  asserted  benefit  when  there  is  free  expectoration. 

ADMINISTRATION.  —  The  best  preparation  is  the  fluid  extract  (FLUID- 
EXTRACTUM  CiMiCiFUG^E,  U.  S.  )  ;  dose,  from  twenty  minims  to  a 
fluidrachm  (1.2-4  C.c.  ).  Tincture  (TiNCTURA  CIMICIFUG^E  —  twenty  per 
cent.,  U.  S.)  ;  dose,  one  to  two  fluidrachms  (4-8  C.c.).  EXTRACTUM 
U.  S.  ;  dose,  five  to  twenty  grains  (0.3-1.3  Gm.  ). 


CAMPHORA  MONOBROMATA.  U.  S.  —  Monobromated  Camphor  or  Bro- 
mated  Camphor.  —  Bromated  camphor  occurs  in  large  acicular  crystals 
several  inches  long. 

Our  present  knowledge  of  the  physiological  properties  of  bromated 
camphor  rests  upon  the  work  of  Bourneville,1  of  Lawson,2  of  Pathault,*  of 
Richard  Peters,*  and  of  Pellicani.5  In  frogs  there  is  progressive  loss  of 
reflex  excitability  and  of  voluntary  movement  (Peters),  which,  according 
to  Pellicani,  is  due  to  paralysis  of  the  motor  nerves.  Death  is  caused  by 
arrest  of  respiration  (Peters).  In  mammals  the  drug  produces  violent 
convulsions,  muscular  weakness  passing  almost  into  paralysis,  reduction 
of  temperature  (after  small  doses  preceded  by  a  rise  —  Peters),  great 
decrease  in  the  rate  of  the  respiration  and  of  the  pulse,  with  occasional 
periods  of  hurried  respiration  (Peters),  profound  sleep  or  stupor,  and 
finally  death.  Bourneville  states  that  the  blood-vessels  of  the  eyes  and 
ears  are  diminished  in  calibre.  Upon  man  the  drug  probably  acts  as  upon 
other  warm-blooded  animals  ;  in  a  case  reported  by  M.  Rosenthal,8  forty- 
five  grains  of  it  caused  tremblings,  marked  slowing  of  the  pulse,  and  coma 
of  six  hours'  duration. 

Bromated  camphor  was  first  introduced  by  Deneffe  7  as  a  nervous  sed- 
ative, and  as  an  antispasmodic,  especially  in  delirium  tremens,  but  is  of 
little  value  ;  it  is  still  used  in  hysteria,  and  has  an  especial  reputation  in 
sexual  excitement  and  spermatorrhoea.  It  is  taken  with  difficulty,  and  is 
apt  to  irritate  the  stomach.  It  is  too  irritant  for  hypodermic  use.  Dose, 
five  to  ten  grains  (0.3-0.6  Gm.  ),  in  capsule  or  coated  pill,  and  repeated 
as  necessary. 

CYPRiPEbiUM,  U.  S.,  is  the  rhizome  and  roots  of  Cypripedium 
pubescens  and  Cypripedium  parviflorum,  to  which  are  attributed  tonic, 
diaphoretic,  and  antispasmodic  properties.  They  are  said  to  contain  a 
volatile  oil  but  no  alkaloids. 

Cypripedin  of  the  drug  stores  is  an  impure  oleoresinous  substance,  the 
dose  of  which  is  given  as  from  one-half  to  three  grains.  Cypripedium  is 
especially  recommended  for  the  allaying  of  functional  nervous  excitability 
and  in  hypochondriasis.  The  fluid  extract,  FLUIDEXTRACTUM  CYPRI- 
PEDII,  U.  S.,  may  be  given  in  doses  of  fifteen  to  thirty  minims  (1-2  C.c.  ). 

AETHER  ACETICUS.  U.  S.  —  Official  Acetic  ether  is  a  transparent, 
colorless,  somewhat  fragrant  liquid,  containing  ten  per  cent,  of  alcohol. 


8o  GENERAL    REMEDIES. 

It  has  been  used  to  a  slight  extent  in  medicine  as  a  stimulant  and  anti- 
spasmodic.  It  resembles  ordinary  ether  somewhat  in  its  action,  but  is 
less  volatile  and  less  rapidly  absorbed  and  eliminated.  It  is  capable  of 
producing  anaesthesia,  but  is  in  every  respect  much  slower  and  less  certain 
in  its  action  than  ordinary  ether,  and  is  practically  of  no  value.  Dose, 
internally,  fifteen  minims  (i  C.c. ). 

SUMBUL.  U.  S. — A  root  supposed  to  be  that  of  Ferula  sumbul  has 
long  been  used  under  the  name  of  -musk-root  as  an  antispasmodic.  It 
contains  two  resins  and  a  volatile  oil,  and  is  a  feeble  nerve  stimulant, 
thought  by  some  to  be  useful  in  amenorrhcea,  hysteria^  and  allied  condi- 
tions. The  dose  of  FLUIDEXTRACTUM  SUMBUL,  U.  S.,  is  thirty  minims. 
Of  the  EXTRACTUM  SUMBUL,  U.  S.,  four  grains  (0.25  Gm. )  ;  but  much 
larger  amounts  may  be  given  without  the  induction  of  distinct  symptoms. 

LACTUCARIUM.  U.  S. — The  concrete  juice  of  the  Lactuca  virosa,*  or  garden 
lettuce,  occurs  as  a  dark  reddish-brown  to  a  light  yellowish,  hard  extract,  having  a 
faintly  narcotic  odor  and  bitter  taste.  A  peculiar  soothing,  hypnotic  influence  has 
been  attributed  to  it,  but  its  activities  are  so  feeble  that  in  a  number  of  trials  with 
very  large  doses  we  have  been  unable  to  perceive  any  effect  whatever.  According 
to  Fronmiiller,1  lactucin  is  even  less  active  than  the  crude  drug.  In  France  lactu- 
carium  is  used  locally  as  a  narcotic  demulcent  in  the  treatment  of  diseases  of  the 
throat.  The  usually  assigned  dose  of  lactucarium  is  thirty  grains  (2  Gm. ),  that  of 
the  fluid  extract  (FLUIDEXTRACTUM  LACTUCARII)  half  a  fluidrachm  (2  C.c.). 
TINCTURA  LACTUCARII — fifty  per  cent,  U.  S.  ;  dose,  one  to  two  fluidrachms 
(4-8  C.c. ).  SYRUPUS  LACTUCARII — ten  per  cent.,  U.  S.  ;  dose,  half  to  one  fluid- 
ounce  (15-30  C.c.).  Much  larger  quantities  may  be  given  without  effect. 


REFERENCES. 

VALERIAN.  2.  LAWSON Practitioner,  1874, 1875. 

i.  BUTTE C.  R.  S.  B.,  1891,  iii.  3-  PATHAULT     .   .   .  Bromure       de      Camphor, 

a.  PARKE Th.  G.,  1887,  167.  Paris,  1875. 

3.  KIONKA D.  M.W.,  Dec.,  1901.  4-  PKTBRS S.  Jb.,  ci.  126. 

4.  SCHWERSENSKI  .    .  Th.  M.,  1897.  5-    PELLICAN1  .    .    .    .  S.  Jb.,  ci. 

6.  ROSENTHAL  .    .    .  S.  Jb.,  ci.  127- 

7.  DENEFFB  ....  Presse  M.  B.,  1871. 

1.  HUTCHINSON  .   .   .  Th.  G.,  1887,  731.  LACTUCARIUM 

2.  YOUNG A.  M.J.S.,  1831,  ix.  LACTUCARIUM. 

CAMPHORA  MONOBROMATA.  ''  FRO™^LER      .  .  Deutsche  Klinik,  1865. 

I.    BOURNEVILLE      .    .  PrOg.  M.,  1874. 

*  For  a  case  of  reputed  poisoning  by  Lactuca  virosa,  see  Schmidt's  Jahrb.,  clxxi.  137. 


FAMILY   II.— ANESTHETICS. 


THE  term  Anesthetics  is  here  employed  as  the  name  of  a  group  of 
volatile  substances,  whose  vapor  has  the  power  of  producing  loss  of  con- 
sciousness, preceded  by  or  accompanied  with  loss  of  sensibility  and  di- 
minished muscular  action.  The  medical  properties  of  these  substances 
are  largely  due  to  their  volatility,  by  virtue  of  which  they  are  very  rapidly 
absorbed  and  almost  as  rapidly  eliminated  by  the  mucous  membrane  of  the 
lungs.  As  a  consequence  of  this,  their  action  is  easily  controlled. 

A  very  large  number  of  theories  have  been  brought  forward  to  account 
for  the  peculiar  effects  of  anaesthetics  ;  of  the  more  important  of  these 
theories  an  elaborate  discussion  may  be  found  in  the  tenth  edition  of  this 
work.  There  is,  however,  nothing  more  mysterious  in  the  action  of 
ether  and  chloroform  upon  the  nerve-centres  than  there  is  in  the  influence 
of  opium  or  strychnine  upon  these  centres,  the  influence  of  the  anaes- 
thetic being  as  certainly  direct  and  vital  as  is  that  of  any  other  drug  which 
acts  upon  human  organs  or  tissues. 

The  action  of  anaesthetics  may  be  modified  by  the  injection  of  nar- 
cotics. Morphine  given  hypodermically  about  half  an  hour  before  the 
exhibition  of  the  anaesthetic  is  said  to  have  a  decided  effect  in  prolonging 
the  anaesthesia.  Chloral  administered  shortly  before  etherization  certainly 
causes  the  first  stages  of  the  latter  to  be  much  quieter  than  usual,  and  also 
prolongs  the  narcosis.  Some  years  since  Neudorfan1  introduced  into 
Berlin  the  use  of  oxygen  gas  with  chloroform  in  the  production  of  anaes- 
thesia ;  more  recently  the  method  has  been  revived  in  America.*  It  has 
even  been  asserted  that  the  oxygen  increased  the  anaesthetic  effect  of  the 
chloroform.  There  is  not  at  present  writing  sufficient  evidence,  however, 
of  the  value  of  the  method. 

The  chief  purposes  for  which  anaesthetics  are  used  are  to  relieve  pain 
and  to  relax  spasm.  To  meet  the  first  indication  they  are  employed  by 
surgeons  especially  ;  but  they  are  also  exceedingly  valuable  in  cases  of 
suffering  from  disease.  It  must  be  borne  in  mind  that  their  action  is 
transitory  and  is  accompanied  by  more  or  less  disturbance  of  the  general 
system,  and  that  consequently  they  are  to  be  employed  only  when  the 
pain  is  exceedingly  severe  and  transient.  To  relieve  pain,  anaesthetics  are 
used  with  great  propriety  during  childbirth.^  In  natural  labor  it  is  not 

*  See  Boston  Med.  and  Surg.  Journ.,  1896,  and  New  York  Med.  Record,  1896. 

t  We  see  no  reason  for  believing  that  anaesthesia  of  the  mother  seriously  influences  the 
child,  and  do  not  think  that  much  weight  can  be  attached  to  the  assertions  of  Hofmeier 
(Berlin.  Klin.  Wochensch.,  1883,  xx.  230)  that  there  is  produced  an  increased  elimination 
of  nitrogen  in  the  new-born  babe. 

6  81 


82  GENERAL   REMEDIES. 

commonly  necessary  to  produce  complete  anaesthesia.  When  the  full 
effect  of  either  ether  or  chloroform  is  induced,  there  is  almost  always  a 
weakening,  and  very  often  an  abolition,  of  the  uterine  contractions.  The 
anaesthetic  should  be  administered  in  such  quantities  as  to  relieve  the  pain 
without  decidedly  interfering  with  the  muscular  spasm.  In  certain  cases 
this  can  be  done,  in  others  it  is  impracticable.  We  have  obtained  advan- 
tageous results  in  some  cases  by  suspending  the  pains  for  about  half  an 
hour  by  means  of  ether,  and  then  entirely  withdrawing  the  anaesthetic. 
By  this  treatment  the  weak,  painful,  ineffectual  efforts  of  a  worn-out,  ner- 
vous patient  may  often  be  converted  into  regular,  successful  efforts.  The 
risk  of  post-partum  hemorrhage  is  materially  increased  by  anaesthetics, 
so  that  it  is  well  to  administer  after  their  use  two  drachms  of  the  fluid 
extract  of  ergot  as  soon  as  the  perineum  is  well  distended  by  the  child's 
head.*  Anaesthetics  are  frequently  used  in  surgery  for  the  purpose  of 
relaxing  spasm,  as  in  cases  of  dislocation,  hernia,  etc.  In  medicine  they 
have  been  employed  in  various  forms  of  convulsions,  and  are  especially 
valuable  in  severe  hysterical  convulsions,  in  puerperal  eclampsia,  and  in 
spinal  convulsions  ;  in  epilepsy  they  are  very  rarely  called  for  ;  in  infantile 
convulsions  they  may  be  sparingly  used  when  the  convulsion  itself  threatens 
life.  In  various  spasms  of  the  excretory  ducts  or  canals,  and  especially 
during  the  passage  of  calculi,  they  act  very  favorably,  both  by  relieving 
pain  and  by  producing  relaxation.  In  asthma,  and  in  spasmodic  stricture 
of  the  oesophagus,  as  in  all  other  cases  of  oft-repeated  spasm,  they  should 
be  administered  only  to  meet  temporary  indications,  as  their  habitual  use 
is  deleterious. 

NITROGEN    MONOXIDE— NITROUS   OXIDE. 

Nitrous  oxide  is  a  colorless,  almost  inodorous,  gas,  of  a  sweetish  taste. 
It  is  a  very  active  supporter  of  combustion.  Water  absorbs  nearly  its 
own  bulk  of  it.  It  is  made  by  the  distillation  of  ammonium  nitrate,  which 
resolves  itself  into  the  gas  and  water.  Nitrous  oxide  gas  is  now  sup- 
plied in  condensed  form.  In  making  nitrous  oxide  the  temperature 
should  never  be  allowed  to  rise  above  482°  F. ,  for  fear  of  generating 
nitric  oxide. 

PHYSIOLOGICAL  ACTION. — The  inhalation  of  pure  nitrous  oxide  gas 
is  followed  in  from  a  half  to  three  minutes  by  unconsciousness,  which 
usually  comes  on  quietly,  but  is  sometimes  preceded  by  hilarious,  erotic, 
or  pugnacious  excitement.  During  the  anaesthesia  the  face  presents  a 
bloated,  swollen,  intensely  livid  appearance. 

The  question  whether  nitrous  oxide  produces  anaesthesia  through  in- 
herent properties  of  its  own,  or  whether  it  acts  simply  by  shutting  oxygen 
off,  has  been  much  discussed  and  variously  answered. 

*  Deaths  from  anaesthetics  are  very  rare  during  parturition,  but  have  occurred.  (See 
C.  B.  Vanzant,  Cincinnati  Lancet,  1893,  xxx.) 


ANESTHETICS.  83 

It  is  well  established  that  nitrous  oxide  will  not  support  life.  A  taper  will  bum 
in  it,  it  is  true,  but  the  liberation  of  oxygen  is  due  to  the  high  heat,  and  at  the 
temperature  of  the  body  nitrous  oxide  is  a  stable  compound. 

In  1864  Ludimar  Hermann,1  as  the  result  of  his  experiments,  came  to  the  con- 
clusion that  the  addition  of  oxygen  to  nitrous  oxide  puts  an  end  to  its  anaesthetic 
properties,  and  that  it  acts  simply  as  an  asphyxiant.  In  1873  MM.  Jolyet  and  T. 
Blanche 2  arrived  at  the  opinion  that  nitrous  oxide  has  no  direct  effect  upon  the  sys- 
tem, and  that  the  narcosis  is  due  to  the  lack  of  oxygen  in  the  body  ;  basing  their 
conclusions  upon  the  following  facts  experimentally  determined  by  them  :  i.  Seeds 
will  not  germinate  in  nitrous  oxide  ;  2.  An  animal  lives  no  longer  in  nitrous  oxide 
than  in  nitrogen  ;  3.  Anaesthesia  occurs  at  the  time  that  the  blood  of  an  animal 
becomes  black  ;  4.  Animals  breathing  an  air  containing  sixty  to  eighty  per  cent,  of 
nitrous  oxide  and  twenty  to  forty  per  cent,  of  oxygen  are  unaffected  ;  5.  Analyses 
of  the  blood  of  two  dogs  yielded  the  following  results  : 

No.  i.    Conscious.  No.  2.    Unconscious. 


Carbonic  acid 46     per  cent. 

Nitrous  oxide 29     per  cent. 

Oxygen 19.7  per  cent. 


Carbonic  acid 36.6  per  cent 

Nitrous  oxide 34.6  per  cent. 

Oxygen 3.3  per  cent. 


And  other  analyses  showed  that  the  coma  was  not  developed  until  the  oxygen  in 
the  blood  was  reduced  to  three  or  four  per  cent. 

The  statements  of  the  French  observers  just  quoted  have  been  abundantly 
corroborated  by  the  observations  of  various  subsequent  investigators.  Colton,* 
Elihu  Thomson,4  and  H.  C.  Wood  have  separately  and  repeatedly  demonstrated 
that  animals  will  live  no  longer  in  nitrous  oxide  than  they  will  in  an  atmosphere 
of  hydrogen  or  nitrogen,  or  even  in  a  vacuum.  In  a  long  series  of  experi- 
ments, H.  C.  Wood5  found  that  two  minutes  and  thirteen  seconds  were  required  to 
produce  complete  anaesthesia  with  pure  nitrous  oxide  gas,  while  in  mechanical  as- 
phyxia the  same  result  was  reached  in  two  minutes  and  nine  seconds.  Thomson  also 
asserts  that  in  man  the  inhalation  of  pure  nitrogen  causes  the  symptoms  of  nitrous 
oxide  narcosis.  H.  C.  Wood  further  determined  that  the  introduction  of  minute 
quantities  of  oxygen  into  nitrous  oxide  prolonged  the  time  necessary  for  the  pro- 
duction of  anaesthesia  in  direct  proportion  to  the  percentage  present,  ten  or  even 
eight  per  cent,  of  oxygen  suspending  entirely  the  anaesthetic  action  of  nitrous  oxide 
gas  upon  the  dog.  The  average  time  required  for  the  production  of  anaesthesia  was 
nearly  doubled  by  the  addition  of  three  per  cent,  of  oxygen,  and  increased  more 
than  twelvefold  by  the  use  of  five  per  cent  of  oxygen.  An  examination  of  the 
analyses  of  blood  given  above  shows  that  the  final  loss  of  consciousness  is  not 
due  to  the  presence  of  carbonic  acid  in  the  liquor  sanguinis,  since  nearly  ten  per 
cent,  more  of  that  gas  was  present  in  the  blood  of  the  conscious  (No.  i)  than  in 
that  of  the  unconscious  dog  (No.  2),  and  also  that  it  is  more  rational  to  believe 
that  the  decrease  in  the  oxygen  rather  than  the  slight  increase  in  the  amount  of 
the  nitrous  oxide  made  the  difference  between  consciousness  and  unconsciousness. 
In  conformity  with  this  are  the  researches  of  C.  A.  MacMunn 6  and  Amory ;  the 
former  observer  finding  that  when  an  animal  is  killed  by  nitrous  oxide  the  arte- 
rial blood  gives  only  spectrum  lines  of  reduced  haemoglobin,  while  after  death  from 
chloroform  the  lines  of  oxyhaemoglobin  are  very  apparent.  Amory 7  demonstrated 
that  during  nitrous  oxide  narcosis  the  amount  of  carbonic  acid  exhaled  from  the 
lungs  is  only  two-thirds  of  that  eliminated  before  the  inhalation,  and  that  immedi- 
ately after  the  recovery  of  consciousness  less  than  one-third  the  normal  amount  of 
carbonic  acid  is  given  off.  If  the  anaesthesia  were  due  to  the  presence  of  carbonic 
acid  in  the  blood,  there  should  be  during  and  immediately  following  the  return  of 
consciousness  great  increase  in  the  elimination  of  this  gas.  It  is  evident,  however, 
that  during  the  whole  narcosis  little  or  no  carbonic  acid  can  be  produced  because 


84  GENERAL   REMEDIES. 

there  is  little  or  no  oxygen  in  the  blood  ;  and  that  consequently  when  the  animal 
recovers  consciousness  there  can  be  no  pronounced  elimination  of  carbonic  acid 
until  by  the  process  of  oxidation  carbonic  acid  is  formed. 

As  inert  gases  produce  symptoms  like  those  of  nitrous  oxide  anaesthesia,  as 
all  these  gases  have  in  common  with  nitrous  oxide  the  function  when  inhaled 
of  shutting  off  the  supply  of  oxygen,  and  as  oxygen  is  necessary  for  the  perform- 
ance of  life  functions,  it  is  natural  to  conclude  that  the  shutting  off  of  the  oxygen  by 
the  nitrous  oxide  is  the  cause  of  the  anaesthesia.  It  has  been  urged  as  an  objection 
to  this  theory  that  the  circulatory  phenomena  produced  by  the  inhalation  of  nitrous 
oxide  are  essentially  different  from  those  of  mechanical  asphyxia. 

It  must,  however,  be  borne  in  mind  that  the  phenomena  of  mechanical  asphyxia 
are  largely  due  to  the  presence  of  an  excess  of  carbonic  acid  in  the  blood,  whilst 
in  the  asphyxia  produced  by  nitrous  oxide  there  is  no  excess  of  carbonic  acid,  so 
that  the  phenomena  present  are  simply  the  outcome  of  a  lack  of  oxygen.  It  is, 
therefore,  a  priori,  to  be  expected  that  the  symptoms  of  mechanical  and  of  nitrous 
oxide  asphyxia  should  differ  to  a  certain  extent.  In  an  elaborate  series  of  experi- 
ments H.  C.  Wood IT  found  that  the  inhalation  of  nitrous  oxide  is  usually  followed 
by  a  rise  of  the  arterial  pressure,  accompanied  by  a  great  disturbance  of  the  pulse  ; 
the  pulse  at  first  becoming  irregular  and  tumultuous,  but  by  and  by  settling,  so  that 
when  anaesthesia  is  complete  the  pulse-wave  is  remarkably  large  and  full  and  the 
rate  very  slow.  The  rise  and  fall  of  the  arterial  pressure  in  nitrous  oxide  anaesthesia 
was  found  to  vary  remarkably,  not  only  in  different  inhalations,  but  at  different 
periods  of  the  same  inhalation.  Sometimes  the  rise  was  sudden,  sometimes  it  was 
gradual ;  sometimes  it  was  maintained  until  near  death,  sometimes  it  was  inter- 
rupted very  early  ;  sometimes  it  was  not  very  well  marked,  sometimes  it  was 
enormous.  Dr.  Amory 7  has  found,  in  experiments  with  the  cerebrometer  upon  the 
dog,  that  there  is,  during  the  anaesthesia,  increased  blood-pressure  in  the  cerebrum, 
with  stasis  in  the  capillaries.  These  results  show  that  the  circulatory  phenomena 
produced  by  nitrous  oxide  resemble  those  of  mechanical  asphyxia  as  closely  as 
could,  a  priori,  be  expected. 

Notwithstanding  all  the  evidence  which  has  just  been  given,  there  is 
much  reason  for  believing  that  nitrous  oxide  has  anaesthetic  properties  ; 
and  that  although  the  unconsciousness  which  is  produced  when  pure 
nitrous  oxide  is  inhaled  is  largely  the  outcome  of  the  deprivation  of 
oxygen,  yet  the  drug  is  capable  of  producing  narcosis  by  its  own  inherent 
properties. 

Martin  Goldstein 8  found  that  when  he  put  frogs  in  an  atmosphere  of  pure  nitrous 
oxide  they  became  motionless,  with  a  complete  loss  of  the  reflexes,  in  fifteen  min- 
utes ;  whilst  when  they  were  put  in  an  atmosphere  of  nitrogen  or  some  other  in- 
different gas  they  preserved  their  irritability  for  some  hours.  It  is  known  that  whilst 
the  nervous  system  of  the  mammal  requires  for  its  activity  the  presence  of  oxygen, 
the  nervous  system  of  the  frog  remains  functionally  active  for  some  hours  after  all 
circulation — that  is,  after  all  carrying  of  oxygen  to  it — has  ceased. 

Believing  that  if  he  could  increase  the  amount  of  nitrous  oxide  in  the  blood  he 
could  get  an  anaesthetic  action  from  it,  Paul  Bert  experimented  by  exposing  the 
animal  in  a  chamber  having  air  so  compressed  that  the  pressure  was  at  least  that  of 
two  atmospheres,  and  found  that  under  these  circumstances  he  could  obtain  anaes- 
thesia with  a  mixture  of  eighty-five  per  cent,  of  nitrous  oxide  and  fifteen  per  cent, 
of  oxygen,  but  that  when  nitrogen  was  substituted  for  nitrous  oxide  no  anaesthesia 
was  produced.  Bert's  method  was  for  a  time  employed  for  the  purposes  of  sur- 
gical anaesthesia  in  Paris  and  in  some  other  capitals  of  Europe,  the  clinical 
records  showing  that  it  is  possible  to  produce  anaesthesia  with  the  gas  in  the  pro- 


ANAESTHETICS.  85 

portion  named  above.  Practically,  however,  the  necessary  apparatus  was  found  to 
be  too  cumbersome  and  expensive  for  use.  In  1881  Klikovitch,  of  St.  Peters- 
burg, used  with  alleged  success  in  parturition  Paul  Bert's  mixture  of  gases  without 
pressure. 

In  1891  Van  Arsdale9  found  that  it  was  possible  in  rare  cases  to  produce  anes- 
thesia in  the  human  being  with  mixtures  of  oxygen  and  nitrous  oxide  in  the  propor- 
tion of  fifteen  to  eighty-five  per  cent. ,  and  that  in  many  cases  a  mixture  in  the  pro~ 
portion  of  ten  to  ninety  per  cent,  would  produce  a  moderately  complete  anaesthesia 
without  cyanosis. 

In  a  research  extending  over  three  years,  F.  W.  Hewitt 10  corroborated  the 
assertions  of  Van  Arsdale,  finding  that  it  is  possible,  in  some  cases  at  least,  to 
produce  deep  and  satisfactory  anaesthesia,  without  obvious  asphyxial  manifestations, 
by  mixtures  of  nitrous  oxide  and  oxygen  containing  even  as  much  of  the  oxygen 
as  is  present  in  our  atmosphere.  George  T.  Kemp  "  made  a  series  of  experiments, 
some  of  which  seem  to  be  very  decisive.  Thus,  an  animal  having  been  anaesthetized 
with  nitrous  oxide,  a  slit  in  the  canula  was  adjusted  so  that  it  let  in  just  sufficient 
air  to  keep  the  animal  alive  and  anaesthetized.  When  nitrogen  was  substituted  for 
nitrous  oxide,  the  amount  of  air  remaining  the  same,  the  dog  gradually  came  out  of 
his  anaesthesia.  Experiments  with  the  blood  showed  that,  though  at  times  perfect 
anaesthesia  existed  with  as  high  a  percentage  of  oxygen  in  the  blood  as  16.8,  it 
usually  was  8.5,  and  sometimes  not  until  the  percentage  was  reduced  to  7.9.  For 
reasons  given  in  his  paper,  which  we  cannot  go  over  here,  Kemp  believes  that  with 
this  amount  of  oxygen  metabolism  remains  about  normal,  a  conclusion,  however, 
which  the  evidence  he  brings  forward  hardly  proves. 

If  nitrous  oxide,  as  the  evidence  at  present  indicates,  is  capable  of 
producing  unconsciousness  by  virtue  of  its  inherent  properties,  it  must 
act  upon  the  cerebrum,  but  it  is  remarkably  inert  in  regard  to  other  por- 
tions of  the  organism.  The  chief  evidence  as  to  its  influence  upon  the 
spinal  cord  is  that  of  Goldstein,  that  it  diminishes  the  reflexes  in  frogs. 
That  its  action  on  the  spinal  cord  is  very  feeble  seems  to  be  shown  by  the 
fact,  which  has  been  repeatedly  asserted,  that  in  human  beings  the  con- 
junctival  reflexes  often  persist  after  deep  anaesthesia  has  been  produced. 

The  experiments  of  Waller  and  of  Amory  show  that  nitrous  oxide 
does  not  affect  the  motor  nerve  trunks.  Ulbrich  believes  that  it  produces 
alterations  in  the  blood,  but  Hermann,  Jolyet  and  Blanche,  Goldstein, 
MacMunn,12  Buxton,13  and  Halliburton  are  in  accord  with  Kemp  in  assert- 
ing that  it  does  not  make  any  compound  with  haemoglobin.  Further, 
Kemp  is  in  accord  with  H.  C.  Wood's  experiments  in  showing  that  it 
has  no  definite  influence  upon  the  heart  or  the  arteries. 

THERAPEUTICS. — Of  all  the  anaesthetics,  nitrous  oxide  is  the  safest. 
It  is  probably  administered  to  more  than  seven  hundred  and  fifty  thousand 
persons  yearly,  and  yet  only  four  recorded  deaths  are  certainly  attributable 
to  it.  *  The  opinion  of  Cartwright u  and  of  W.  Ottley , 15  that  in  cases  of  heart 
disease  permanent  increase  of  the  cardiac  weakness  is  caused  by  nitrous  gas 
inhalation,  is  not  established.  The  final  fall  of  blood-pressure  produced  by 

*  Not  including  the  case  reported  in  the  Dental  Cosmos,  June,  1872.  (See  Brit. 
Journ.  Dent.  Sci.,  Feb.  1873  ;  Brit.  Med.  Journ.,  1877,  i.  460;  Ibid.,  1883,  ii.  729;  Dent, 
and  Surg.  Microcosm,  Oct.  1895.)  In  one  of  these  cases  the  result  is  said  to  have  been 
due  to  syncope. 


86  GENERAL   REMEDIES. 

the  gas  was  found  in  the  experiments  of  H.  C.  Wood  to  be  due  to  paral- 
ysis of  the  vaso-motor  apparatus,  probably  of  asphyxial  origin,  and  death 
always  occurred  from  respiratory  paralysis,  the  heart  continuing  to  beat 
powerfully  after  respiration  had  ceased  and  the  arterial  pressure  had  fallen 
very  low.  Even  when  alarming  symptoms  occur  during  nitrous  oxide 
anaesthesia,  the  results  are  very  rarely  disastrous,  because  the  loss  of  func- 
tion has  been  due,  not  to  the  presence  of  a  poison,  but  to  the  absence  of 
oxygen,  and  although  the  paralysis  may  be  complete,  the  life-power  sleeps 
before  it  dies,  and  is  ready  to  react  to  oxygen.  Immediate  artificial  res- 
piration is  the  one  remedy  for  the  treatment  of  alarming  symptoms  during 
nitrous  oxide  asphyxia. 

In  diseases  of  the  kidney  nitrous  oxide  is  probably  far  safer  than  any 
of  the  liquid  anaesthetics,  since  in  the  experiments  of  Thomson  and  Kemp  18 
it  was  found  to  have  no  other  effect  upon  the  kidneys  than  that  which  it 
exerted  upon  the  general  circulation.  Experience  has  not  confirmed  the 
assertion  of  Lafont,  that  nitrous  oxide  anaesthesia  is  prone  to  be  fol- 
lowed by  miscarriage,  chlorosis,  and  epilepsy.  His  especial  warning 
against  the  production  of  diabetes  mellitus,  and  his  statement  that  glyco- 
suria  may  be  produced  by  the  drug  in  the  dog,  remain  unconfirmed  by 
clinical  or  experimental  evidence,  although  a  well-known  Philadelphia 
surgeon  persistently  attributed  his  own  fatal  diabetes  to  the  use  of  nitrous 
oxide.  In  experiments  made  by  George  S.  Woodward  and  Alfred  Hand 
in  the  laboratory  of  the  University  of  Pennsylvania  it  was  found  impos- 
sible to  produce  glycosuria  in  the  dog.  On  account  of  the  high  blood- 
pressure  with  venous  stasis  which  occurs  during  nitrous  oxide  anaesthesia, 
atheroma  or  other  diseases  of  the  arterial  walls  should  be  considered  a 
centra-indication  to  the  use  of  the  gas,  and  fatal  apoplexy  *  has  occurred 
during  or  immediately  after  its  administration. 

ADMINISTRATION. — The  difficulty  with  the  practical  use  of  nitrous 
oxide  for  other  than  the  brief  anaesthesia  required  in  teeth  extraction  and 
other  forms  of  minor  surgery  has  been  the  extreme  fugaciousness  of  the 
anaesthesia,  as  well  as  the  asphyxial  symptoms  always  present.  It  is 
affirmed  that  these  difficulties  are  overcome  by  the  consentaneous  use  of 
oxygen  with  the  gas.  Undoubtedly  the  asphyxial  symptoms  are  greatly 
lessened,  but  the  allegation  that  the  period  of  recovery  after  the  with- 
drawal of  the  gas  is  distinctly  prolonged  has  not,  in  our  experience,  been 
sustained.  In  various  cases  we  have  noticed  the  return  to  conscious- 
ness as  complete  in  from  twenty-eight  to  forty  seconds.  With  great 
care  in  the  administration  of  the  mixed  gases,  the  anaesthesia  can  be,  it 
is  true,  almost  indefinitely  prolonged,  but  the  danger  of  recovery  at  any 
moment  is  great.  It  is  common  for  operators  to  vary  the  percentage 
of  oxygen  according  to  the  appearance  of  the  patient,  often  giving  first 
pure  nitrous  oxide  and  adding  oxygen  without  any  definite  measure- 
ment when  the  asphyxial  symptoms  set  in  ;  watching  the  effect  of  the 

*  See  Dental  Cosmos,  1890 ;  also  Therap.  Gaz.,  1896,  xii. 


ANAESTHETICS.  87 

oxygen  and  increasing  or  lessening  it  according  to  the  facial  expression 
of  the  patient.  Matthew  H.  Cryer,  of  the  University  Dental  Faculty, 
states  that  the  apparatus  prepared  in  London  according  to  Hewitt's 
plan  is  impracticable  owing  to  the  fact  that  an  easy  reflux  is  afforded  for 
the  two  gases  into  each  other,  and  has  worked  out  an  apparatus  which 
seems  to  be  satisfactory  and  is  not  over-cumbersome.  The  method  is 
certainly  a  distinct  advance,  in  that  it  enables  the  operator  at  any  mo- 
ment to  have  the  subject  breathe  pure  oxygen  if  disagreeable  symptoms 
occur. 

Nitrous  oxide  is  sometimes  used  in  conjunction  with  ether,  the  primary 
anaesthesia  of  nitrous  oxide  allowing  the  patient  to  pass  under  the  ether 
without  the  unpleasant  excitement.  Le  Breton  18  is  probably  correct  in 
his  belief  that  this  method  is  safer  than  ether  alone,  because  of  the  smaller 
amount  of  ether  required. 


—  ETHER.     U.  S. 

Ethyl  oxide  is  a  colorless,  very  volatile  liquid,  obtained  by  the  dehy- 
dration of  alcohol  by  sulphuric  acid.  It  is  very  inflammable,  as  is  also  its 
vapor,  which  is  two  and  a  half  times  heavier  than  air.  It  is  freely  soluble 
in  alcohol,  and  is  itself  a  powerful  solvent.  Its  odor  is  strong  and  peculiar  ; 
its  taste  is  hot.  Its  specific  gravity,  when  pure,  is  0.713,  and  its  boiling 
point  95°  F.  Ether  of  the  U.  S.  Pharmacopoeia  contains  ninety-six  per 
cent,  of  ethyl  oxide,  and  should  boil  "when  a  test-tube,  containing  some 
broken  glass  and  half  filled  with  it,  is  held  for  some  time  in  the  hand.  '  ' 

Locally,  ether  is  a  violent  irritant  ;  it  is  absorbed  with  rapidity 
through  the  mucous  membranes  both  of  the  lungs  and  of  the  gastro- 
intestinal tract.  When  taken  freely  it  is  eliminated  largely  unchanged  by 
the  lungs. 

PHYSIOLOGICAL  ACTION.  —  The  first  effects  of  ether  when  inhaled  are 
burning  in  the  fauces  and  a  feeling  of  strangulation,  each  due  to  the  local 
impression  of  the  irritant  vapor.  The  primary  indications  of  its  systemic 
action  are  a  sense  of  exhilaration  and  a  lightness  in  the  head,  associated 
with  a  roaring  or  buzzing  in  the  ears.  These  are  soon  succeeded  by  a 
feeling  of  the  immediate  surroundings  being  afar  off,  which  soon  fades 
into  semi-unconsciousness,  with  visions  and  illusions.  These  are  of  vari- 
ous characters,  and  are  often  accompanied  by  a  species  of  delirium.  Some 
patients  weep,  others  laugh  ;  some  shout,  some  pray,  some  rave,  and 
some  become  exceedingly  pugnacious.  In  rare  instances  the  dreams 
are  erotic  ;  and  cases  are  on  record  in  which  there  were  distinct  evi- 
dences of  the  occurrence  of  a  complete  venereal  orgasm.  In  this  stage 
the  patient  in  most  cases  may  be  more  or  less  perfectly  aroused.  There 
is  rarely  sufficient  anaesthesia  for  practical  purposes  before  the  period  of 
complete  unconsciousness. 

The  second  stage  of  ether-narcosis  may  be  considered  to  begin  with 
the  complete  loss  of  consciousness.  Muscular  rigidity  may  persist  for  a 
length  of  time,  but  usually  it  soon  passes  off,  and  the  patient  lies  relaxed 


88  GENERAL    REMEDIES. 

and  quiet,  with  slow,  regular,  automatic  respiration.  *  The  occurrence  of 
stertorous  respiration,  due  to  a  paresis  of  the  muscles  of  the  palate,  shows 
that  the  stage  of  muscular  paralysis  is  being  reached.  It  should,  except 
in  rare  cases,  be  the  signal  for  the  immediate  withdrawal  of  the  anaesthetic. 
The  face  during  etherization  is  reddish  ;  marked  pallor  and  lividity  are 
respectively  important  indications  of  failure  of  the  heart's  action  and 
failure  of  respiration.  The  stage  of  excitement  generally  lasts  only  a  few 
minutes,  but  in  some  cases  is  prolonged,  and  in  nervous  women  may  pass 
into  a  violent  fit  of  hysterics,  which  soon  yields,  however,  to  a  persistent 
use  of  the  anaesthetic.  The  pulse  is  quickened  and  increased  in  force  by 
ether,  and  it  will  often  maintain  itself  during  a  prolonged  narcosis.  If  the 
vapor  of  ether  be  taken  in  a  concentrated  form,  there  is  often  in  the 
beginning  a  momentary  arrest  of  respiration,  accompanied  by  a  decided 
sense  of  suffocation,  evidently  the  result  of  the  irritant  action  of  the  vapor 
upon  the  upper  air-passages.  So  soon  as  this  has  passed  off,  the  respira- 
tions are  usually  accelerated  as  well  as  deepened  ;  but  as  the  stage  of 
anaesthesia  is  reached  they  become  slower,  and,  if  the  inhalation  of  the 
ether  be  persisted  in,  they  grow  not  only  more  and  more  distant,  but  also 
more  and  more  shallow,  until  they  are  gradually  extinguished. 

The  respiratory  phenomena  seem  to  be  the  same  in  the  lower  mammalia  as  in 
man.  The  primary  arrest  of  respiration  during  the  first  stages  of  etherization  is 
undoubtedly  due  to  a  local  irritation  of  the  mucous  membranes  of  the  air-passages. 
According  to  Kratschmer,1  in  the  rabbit  it  is  prevented  by  previous  section  of  the 
trigeminal  nerves,  but  not  by  division  of  the  vagi ;  nor  does  it  occur  when  the  ether 
is  administered  through  a  tracheal  fistula.  This  would  indicate  that  the  respiratory 
disturbance  is  due  to  irritation  of  the  peripheral  trigeminal  nerves,  but  H.  A.  Hare  * 
has  found  that  in  the  dog  tracheal  irritation  with  ether  produces  respiratory  arrest, 
which  is,  however,  prevented  by  previous  section  of  the  vagus.  As  stated  by 
P.  Knoll,3  the  arrest  of  respiration  is  sometimes  replaced  by  very  irregular  breath- 
ing. The  importance  of  the  matter  is  increased  by  the  fact  that  Kratschmer  has 
noticed  that  the  disturbances  of  respiration  are  accompanied  by  spasm  of  the 
glottis.  It  is  evident  that  these  disturbances  are  reflexes  due  to  irritation  of  the 
trigeminal  nerves  in  the  upper,  and  of  the  pneumogastric  filaments  in  the  lower 
respiratory  tract.  They  are  especially  interesting  in  connection  with  the  asserted 
direct  or  indirect  effect  of  ether  upon  the  recurrent  laryngeal  nerve,  f 

It  is  possible,  but  not  probable,  that  some  of  the  accidents  which  have 
happened  early  in  human  anaesthesia  have  been  due  to  these  respiratory 
reflexes  ;  the  important  practical  fact  is  that  aberrations  of  respiration  occur- 

*  For  a  full  discussion  of  motor  phenomena  during  profound  anaesthesia,  see  Rudolf 
Jaksch  (  Wien.  Med.  Wochensch.,  1889,  xxxix.  359). 

t  F.  H.  Hooper  was,  we  believe,  the  first  to  note  that  stimulation  of  the  recurrent 
laryngeal  nerve  causes  a  dilatation  of  the  glottis  in  the  thoroughly  etherized  dog,  although 
in  the  normal  animal  it  always  produces  a  constriction.  This  remarkable  observation 
has  given  rise  to  several  investigations,  the  most  extended  of  which  is  that  of  H.  P.  Bow- 
ditch  (Amer.Journ.  Med.  Set.,  1887,  xciii.),  to  which  the  reader  is  referred  fora  full  sum- 
mary and  discussion  of  the  matter.  Dr.  Bowditch  corroborates  the  observation  of  Hooper, 
and  also  finds  that  during  partial  etherization  weak  irritation  of  the  recurrent  nerves 
causes  dilatation  and  strong  irritation  constriction  of  the  glottis.  As  yet  no  satisfactory 
explanation  of  these  curious  phenomena  has  been  offered. 


ANESTHETICS.  89 

ring  in  the  beginning  of  an  etherization  are  to  be  overcome  by  persistence 
in  the  inhalation,  after  which  the  respirations  will  become  slower,  deeper, 
and  more  regular  ;  indeed,  as  pointed  out  by  Kronecker,4  the  late  and  dan- 
gerous arrest  of  respiration  during  anaesthesia  occurs  only  after  the  reflex 
function  has  been  abolished.  When  the  administration  is  continued  to  the 
end,  the  respirations  become  very  slow  and  more  and  more  shallow  until 
extinguished.  Irregularities  of  respiration  occurring  in  the  later  stages 
of  an  etherization  are  of  the  most  serious  import,  and  demand  immediate 
withdrawal  of  the  drug.  Clinical  experience  confirms  the  experimental 
proof  obtained  by  Knoll,  that  these  late  disturbances  of  respiration 
are  the  result  of  the  direct  influence  of  the  drug  upon  the  respiratory 
centres. 

According  to  Eulenberg,5  in  the  beginning  of  anaesthesia  produced 
either  by  ether  or  by  chloroform,  the  knee-jerk  in  man  is  increased  ; 
when  chloroform  is  employed,  this  increase  soon  disappears,  but  with 
ether  it  endures  even  into  the  narcosis. 

Upon  the  lower  animals  ether  acts  as  upon  man,  and  it  has  been 
shown  by  Claude  Bernard 6  that  the  most  primitive  infusoria  are  suscepti- 
ble to  its  influence. 

Both  in  man  and  the  lower  animals  the  cerebral  functions  are  the  first 
to  be  affected  by  ether.  According  to  the  experiments  of  H.  C.  Wood, 
Jr.,7  when  the  ether  is  given  in  such  a  manner  to  the  dog  as  to  avoid  all 
violence  of  administration,  and  in  minute  dose,  the  first  positive  indication 
of  the  loss  of  intellection  is  failure  of  the  perception  and  interpretation  of 
sound,  the  sense  of  sight  lasting  somewhat  longer.  Loss  of  coordination 
and  loss  of  motor  power,  though  with  a  continuation  of  movement,  are 
the  next  phenomena.  It  was  further  demonstrated  in  these  experiments 
that  there  is  a  stage  of  ether  narcosis  in  which  the  sensibility  is  distinctly 
lessened,  although  no  motor  changes  are  demonstrable.  This  affords 
confirmation  of  the  early  experiments  of  Flourens,8  who  found  that  the 
order  in  which  during  etherization  the  power  of  responding  to  pricking  is 
lost  was,  first,  in  the  posterior  or  sensory  portion  of  the  spinal  centres  ; 
second,  in  the  anterior  or  motor  portions  of  the  spinal  cord  ;  and,  third, 
in  the  medulla  oblongata.  Longet 9  has  confirmed  this  order,  except  that 
by  using  powerful  galvanic  currents  he  was  able,  even  in  the  deepest 
narcosis,  to  get  a  response  from  the  anterior  portion  of  the  cord. 

The  order  of  the  involvement  of  the  nerve-centres  in  man  and  animals 
is — first  the  cerebrum,  next  the  sensory  centres  of  the  cord,  next  the 
motor  centres  of  the  cord,  next  the  sensory  centres  of  the  medulla  ob- 
longata, and  finally  the  motor  centres  of  the  medulla  oblongata. 

Waller 10  found  that  if  he  brought  dilute  ether  or  chloroform  vapor  in 
direct  contact  with  a  motor  nerve,  that  nerve  lost  its  power  of  transmit- 
ting electrical  impulses.  If  the  vapor  had  not  been  too  concentrated,  the 
nerve  recovered  its  function  after  removal  of  the  anaesthetic.  The  recovery 
after  chloroform  was  less  rapid  than  after  ether.  If  the  observations  of 
Longet  (loc.  cit.,  382)  and  Serres17  be  correct,  the  sensory  nerve-fibres 


90  GENERAL   REMEDIES. 

are  more  susceptible  to  the  influence  of  ether  than  are  the  motor.  They 
found  it  possible,  however,  by  the  direct  application  of  ether  to  a  nerve, 
to  produce  a  condition  in  which  pinching  the  nerve  below  the  point  of 
application  caused  no  pain,  although  voluntary  movement  was  preserved, 
and  galvanization  of  the  nerve-trunk  above  the  point  of  application  in- 
duced spasms  in  the  tributary  muscles, — i.e.,  the  power  of  conducting 
an  impulse  downward  was  preserved,  that  of  conducting  it  upward  was 
lost.  By  a  longer  application  of  the  anaesthetic  the  function  of  the 
efferent  as  well  as  of  the  afferent  fibres  was  abolished,  temporarily  at 
first,  but,  if  the  application  were  persisted  in,  permanently. 

Owing  to  the  great  sensitiveness  of  the  nerve-centres  in  man,  most  if 
not  all  of  the  phenomena  of  etherization  are  of  centric  origin.  Indeed, 
Conly  "  found  that  in  animals  killed  by  ether,  chloroform,  or  chloral,  the 
motor  nerves  and  muscles  preserve  their  function  longer  than  in  animals 
killed  by  sudden  violence.  Nevertheless,  F.  S.  Locke12  found  that  in 
the  frog,  at  least,  the  muscles  are  directly  affected  by  etherization  ;  there 
being  not  only  a  lessening  of  the  height  of  the  contraction  under  stimula- 
tion, but  also  an  alteration  in  its  form. 

Upon  the  motor  system  of  organic  life  ether  certainly  acts,  but  much 
less  energetically  than  upon  the  voluntary  system.  Thus,  after  death 
from  ether  the  vermicular  movements  of  the  intestine,  although  less 
active  than  normal,  are  very  rarely,  if  ever,  entirely  absent. 

Wright18  has  demonstrated  histological  changes  in  the  pyramidal  cells 
of  the  nervous  centres  due  to  the  administration  of  ether  or  chloroform. 
The  more  prolonged  the  exposure  to  the  anaesthetic,  the  slower  is  the 
return  to  the  normal. 

Circulation. — The  first  effect  of  ether  is  usually  to  cause  a  pronounced 
rise  in  the  arterial  pressure,  which  is  commonly  maintained  even  through 
a  prolonged  ether  narcosis,  and  may  continue  until  manifest  failure  of  res- 
piration ;  usually,  however,  it  is  after  a  time  succeeded  by  a  fall  of  pressure. 
Blauel  found,  in  tonometrical  studies  upon  man,  that  during  ether  anaes- 
thesia the  pressure  is  raised  in  seventy-nine  per  cent,  of  the  cases,  not 
affected  in  nine  per  cent. ,  lowered  in  twelve  per  cent.  What  evidence  we 
have  upon  the  subject  indicates  that  the  primary  action  of  ether  upon  the 
heart  is  that  of  a  stimulant,  though  later  if  in  sufficient  amount  it  un- 
doubtedly acts  as  a  cardiac  depressant ;  that  this  depressing  action  is 
feeble,  is  shown  by  the  experiments  of  Tunnicliffe  and  Rosenheim,  who 
found  that  in  the  excised  mammalian  heart  two  per  cent,  of  ether  in  the 
blood  did  not  stop  the  heart. 

The  rise  of  blood-pressure  appears,  however,  not  to  be  entirely  cardiac, 
since  Sansom13  found  that  the  vessels  of  the  frog's  web  are  thrown  into  a 
persistent  spasm  by  the  inhalation  of  ether  ;  and  Bowditch  and  Minot M 
conclude  as  the  result  of  their  experiments  that  in  the  mammal  the  drug 
first  stimulates,  afterwards  depresses,  the  vaso-motor  centres. 

Blood. — It  is  frequently  asserted  that  ether  when  added  to  blood 
coagulates  it.  A.  Schmidt,  however,  states  that  the  coagulation  is  due 


ANAESTHETICS.  9I 

to  ozone  which  has  been  generated  in  the  ether,  since  freshly  distilled 
ether  does  not  coagulate  albuminous  substances. 

The  researches  of  Wittich 15  and  of  A.  Schmidt 16  have  shown  that  when 
ether  is  added  to  the  blood  of  horses,*  cats,  or  rats,  the  red  corpuscles 
disappear  in  a  very  short  time,  and,  as  their  stroma  cannot  be  demon- 
strated by  the  aid  of  reagents,  this  disappearance  is  due  to  its  solution. 
The  oxyhaemoglobin  thus  set  free  is  dissolved  in  the  serum,  but  the  pres- 
ence of  the  ether  soon  causes  it  to  crystallize.  There  is  no  proof  that 
these  changes  occur  to  any  extent  when  ether  is  inhaled  ;  and  the  usual 
rapid  recovery  from  the  effects  of  the  anaesthetic  indicates  that  there  is  no 
profound  alteration  of  the  blood,  f 

An  imperfect  study  by  Harley  of  the  effect  of  ether  on  the  gases 
contained  in  drawn  blood  indicates  that  ether  does  not  exert  much  in- 
fluence upon  their  proportional  amounts.  It  is,  however,  quite  possible 
that  a  more  thorough  investigation  would  give  a  different  result.  J 

SUMMARY.— Locally  ether  is  a  violent  irritant.  In  excess  it  prob- 
ably depresses  all  higher  tissues,  but  it  especially  acts  upon,  first,  the 
cerebrum,  next  upon  the  sensory,  and  then  upon  the  motor  side  of  the 
spinal  cord.  It  usually  produces  death  by  asphyxia,  due  to  depression 
of  the  respiratory  centres.  Its  first  action  upon  the  circulation  is  that 
of  a  stimulant  to  the  heart,  and  perhaps  also  to  the  vaso-motor  cen- 
tres. The  large  dose  finally  depresses  both  heart  and  blood-vessels. 

THERAPEUTICS. — For  a  discussion  of  the  use  of  ether  as  an  anaesthetic, 
see  page  104. 

Administered  by  the  mouth,  ether  has  been  used  with  advantage  in 
various  forms  of  colic,  but  is  generally  inferior  to  chloroform.  When, 
however,  as  in  cases  of  retrocedent  or  internal  gout,  there  is  with  the 
painful  gastric  and  intestinal  spasm  a  condition  bordering  on  collapse,  the 
stimulant  properties  of  ether  make  it  very  valuable. 

In  sudden  sinking -spells,  either  from  poison  or  from  natural  causes, 
ether,  as  a  powerful  and  very  quickly  acting  stimulant,  is  often  indicated. 
In  some  cases  of  this  description  it  may  even  be  administered  by  inhala- 
tion. Of  course,  under  these  circumstances,  its  influence  should  not  be 
carried  nearly  to  the  point  of  producing  anaesthesia. 

As  an  anthelmintic,  ether  has  been  used  with  asserted  success  against 
the  tape-worm.  For  this  purpose,  an  ounce  and  a  half  have  been  ad- 
ministered at  once,  followed  in  two  hours  by  a  full  dose  of  castor  oil. 

In  hysteria,  neuralgia,  nervous  headache,  and  spasmodic  neuroses, 
such  as  hiccough  and  asthma,  ether  is  occasionally  employed  with  benefit. 

*  Schmidt  (loc.  cil.,  23)  says  that  sometimes  crystallization  fails  in  the  blood  of  the 
horse. 

t  On  the  continent  of  Europe,  ether  is  used  hypodermically  as  a  cardiac  stimulant. 
In  a  number  of  cases,  however,  it  has  produced  local  paralysis  of  neuritic  origin. 

J  For  literature,  cases,  and  discussion,  see  Schulz,  Deutsch.  Militar.  Zeitsch.,  1903, 


92  GENERAL   REMEDIES. 

When  ether  is  swallowed,  it  produces  a  sense  of  strangulation  and 
choking  which  seriously  interferes  with  its  use.  For  this  reason,  it  i= 
often  given  in  capsules,  or  in  ice-cold  water.  Probably  large  doses  are 
best  administered  by  putting  them,  mixed  with  an  equal  amount  of  brandy, 
on  finely  cracked  ice  before  drinking.  The  dose  is  from  one  fluidrachm 
to  half  a  fluidounce  (4-15  C.c. ). 

Etherization  by  the  rectum  has  been  tried,  but  has  been  discarded  on 
account  of  the  severe  irritation  of  the  rectum  and  lower  bowel  which  it 
causes,  as  well  as  because  of  the  slowness  of  the  production  of  insensi- 
bility. 

CHLOROFORMUM— CHLOROFORM. 

METHENYL  CHLORIDE. 

This  substance,  which  was  discovered  in  1831  by  Samuel  Guthrie, 
of  Sackett's  Harbor,  New  York,  is  produced  by  the  action  of  chlorine 
upon  alcohol.  It  is  a  colorless,  limpid,  and  neutral  fluid,  which  is  for 
practical  purposes  non-inflammable,  although  it  can  be  made  to  burn  with 
a  greenish  flame.  Its  taste  is  hot  and  sweetish,  its  odor  fragrant  and 
peculiar.  It  is  soluble  in  alcohol  and  in  ether,  but  when  dropped  into 
water  it  sinks,  if  pure,  as  transparent  globules  without  milkiness.  The 
alcoholic  solution,  when  moderately  diluted  with  water,  forms  an  aromatic, 
sweetish  liquid.  It  is  antiseptic,  and  does  not  coagulate  albumin. 

The  U.  S.  Pharmacopoeia  recognizes  Chloroform,  and  requires  that  it 
should  contain  by  weight  99  to  99.4  per  cent,  of  absolute  chloroform  and 
o.  6  to  i  per  cent,  of  alcohol. 

PHYSIOLOGICAL  ACTION. — Local  Effects. — Although  somewhat  of 
an  anaesthetic,  chloroform  applied  locally  is  a  powerful  irritant.  On  the 
skin  it  produces  redness  and  burning  ;  if  the  evaporation  be  restrained, 
vesication  will  be  induced  by  it.  Taken  into  the  mouth,  it  causes  a 
burning  sensation,  and,  when  swallowed,  a  sense  of  warmth  in  the 
stomach. 

Absorption  and  Elimination. — Chloroform  is  rapidly  absorbed  through 
the  mucous  membrane  of  the  respiratory  and  digestive  apparatus.  Its 
exact  fate  in  the  body  is  at  present  unknown.  It  is  certainly  eliminated, 
at  least  in  part,  unchanged  in  the  expired  air  after  administration  by  the 
mouth  (Benedicenti1);  and  after  its  inhalation  has  been  detected  by 
Fubini  and  by  Siolfatti  *  in  the  urine.  It  is  probably,  however,  in  part 
decomposed  in  the  system,  since  A.  Zeller s  has  found  that  the  chlorides 
of  the  urine  are  nearly  doubled  by  its  inhalation. 

The  vapor  of  chloroform,  when  inhaled,  produces  symptoms  seemingly 
similar  to  those  induced  by  ether,  except  that  the  choking  sensations  are 
absent,  and  that  the  stage  of  excitement  is  generally,  but  not  always, 
shorter  and  less  violent  than  is  that  of  etherization. 

General  Action. — The  division  of  chloroform-narcosis  into  three  stages 
was  first  proposed  by  Sabarth,4  and,  though  somewhat  arbitrary,  is  prac- 
tically useful.  In  the  first  of  these  the  symptoms  are  similar  to  those  of 


ANAESTHETICS.  93 

alcoholic  intoxication.  This  stage  is  generally  very  short,  but  in  athletic 
persons,  and  especially  in  those  who  have  been  intemperate,  it  may  be 
very  long  and  very  violent,  and  may  persist  after  loss  of  consciousness. 
In  drunkards,  this  excitement  at  times  cannot  be  overcome  without  grave 
danger  to  life.  During  this  first  stage,  although  consciousness  is  not 
lost,  the  sensibility  is  generally  blunted,  but  very  rarely  is  it  altogether 
annulled.  Coleman  (Sansom,  Chloroform,  55,  Philadelphia,  1866)  states, 
however,  that  he  has  extracted  his  own  teeth  without  pain  ;  and  Snow  re- 
lates the  anecdote  of  a  child  who  played  with  his  toys  during  the  operation 
of  lithotomy. 

During  the  second  stage,  which  is  that  of  anaesthesia,  the  conscious- 
ness and  sensibility  are  abolished,  the  muscles  are  relaxed,  and  the  patient 
lies  perfectly  quiet.  This  is  the  surgical  stage,  during  which  ordinary 
operations  are  performed.  As  already  intimated,  in  some  cases  the  first 
and  second  stages  are  united,  so  that  violent  excitement,  muscular  spasm, 
and  rigidity  may  coexist  with  loss  of  consciousness  and  of  sensibility. 

The  third  stage  is  one  of  profound  narcosis,  with  stertorous  breathing, 
intense  muscular  relaxation,  abolition  of  the  ordinary  reflexes,  and  fall  of 
bodily  temperature.*  This  is  always  a  condition  of  danger,  and  its  in- 
duction by  chloroform,  except  under  very  peculiar  circumstances,  is  un- 
justifiable. 

The  pulse  in  the  first  stage  of  chloroform -narcosis  may  be  quickened, 
even  apparently  strengthened  ;  in  the  second  stage  it  is  generally  about 
normal  in  frequency,  but  is  more  or  less  weakened  ;  in  the  third  stage 
it  is  rapid  and  weak.  Noel 5  calls  attention  to  a  cervical  venous  pulse, 
most  marked  in  the  external  jugulars,  which  he  asserts  frequently  occurs 
during  the  waking  up  from  chloroformization.  He  believes  it  to  be  a 
symptom  of  serious  cardiac  embarrassment.  E.  Simonin 6  found  that  the 
temperature  usually  rises  during  the  first  stage  (o.  i°-o.9°  C. ),  falls  slightly 
during  the  second  or  remains  above  normal,  and  falls  decidedly  during 
the  third  stage,  f 

*  Baudin  (Le  Progres  Med.,  Sept.  1874)  called  attention  to  the  pupil  as  a  guide  in 
chloroformization,  stating  that,  although  at  first  it  is  uniformly  dilated,  afterwards  it  is 
uniformly  immovably  contracted,  and  that  this  is  the  period  for  operating.  Schlager  is 
in  accord  with  Baudin ;  in  one  hundred  and  twenty  out  of  one  hundred  and  twenty-two 
cases  observed,  the  pupil  was  dilated  during  the  stage  of  excitement,  and  during  com- 
plete anaesthesia  narrowly  contracted.  He  also  states  that  if  during  anaesthesia  the  pupil 
return  to  normal,  more  chloroform  is  required,  but  if  it  suddenly  dilate,  danger  is  immi- 
nent. At  present,  however,  the  condition  of  the  pupil  cannot  be  considered  a  safe  guide 
in  anaesthetization.  Dogiel  (Reicherfs  Archiv  fur  Anal.,  1866)  affirms  that  in  rabbits, 
during  the  stage  of  excitement,  the  pupil  is  contracted,  during  anaesthesia  dilated.  Schiff 
has  strenuously  combated  the  conclusions  of  Baudin  ;  and  in  a  very  careful  series  of  ex- 
periments on  animals  W.  H.  Winslow  found  that  the  state  of  the  pupil  varies  greatly  in 
the  same  stage  of  anaesthesia.  Thus,  in  complete  anaesthesia,  sometimes  the  pupil  was 
widely  dilated,  sometimes  contracted ;  and  death  sometimes  occurred  with  a  dilated, 
sometimes  with  a  contracted  pupil,— in  the  former  case  probably  being  syncopal,  in  the 
latter  asphyxial  (Phila  Med.  Times,  vi.  275). 

fAs  the  result  of  chemical  studies,  Julius  Pohl  (Arch.  f.  E.rfi.  Pathol.  n.  Pharm., 
1891,  xxviii.)  believes  that  more  chloroform  exists  during  the  narcotic  period  in  the  brain- 
tissue  than  in  the  blood  coming  to  it. 


94  GENERAL   REMEDIES. 

The  experiments  of  Holmgren,  Kratschmer,  H.  C.  Wood;  Jr.,7  and 
others  have  demonstrated  that  the  action  of  chloroform  upon  the  nervous 
system  is  entirely  parallel  to  that  of  ether  (see  page  88),  the  difference 
being  simply  one  of  intensity  of  power.  In  practical  anaesthesia  the  stage 
of  excitement  is  usually  much  less  severe  with  chloroform  than  with  ether, 
but,  according  to  H.  C.  Wood,  Jr.,  this  hyperexcitation  depends  largely 
upon  the  ether  vapor  being  too  concentrated  ;  when  the  anaesthesia  was 
induced  in  animals  slowly  with  a  very  small  percentage  of  ether  in  the  air, 
the  stage  of  excitement  was  greater  with  chloroform  than  with  ether. 
The  motor  disturbances  seen  early  in  chloroformization,  as  in  etherization, 
have  been  supposed  to  indicate  a  condition  of  spinal  stimulation,  but  have 
been  shown  by  Bert 8  to  be  of  purely  psychical  origin. 

Bernstein 9  found  that  there  was  no  perceptible  difference  in  the  con- 
ducting power  of  the  two  ischiatic  nerves  of  a  frog  chloroformed  after  one 
of  its  iliac  arteries  had  been  tied. 

Circulation. — In  some  animals  the  first  effect  of  the  inhalation  of  chlo- 
roform upon  the  circulation  is  a  decrease  in  the  frequency,  of  the  heart's 
action.  Dogiel  believes  that  this  is  due  to  a  stimulation  of  the  inhibitory 
centres,  because  he  has  found  that  it  does  not  occur  after  section  of  the 
vagi.  The  after-increase  in  the  rapidity  of  the  pulse  appears  to  be  due,  at 
least  in  part,  to  paralysis  of  the  inhibitory  centres,  upon  which  chloroform 
seems  to  act  as  upon  the  oculo-motor  centres,  producing  in  them  at  first 
excessive  functional  activity,  but  afterwards  functional  paralysis.  Both 
Kratschmer  and  Knoll  (see  page  88)  have  noticed  in  rabbits,  when  either 
ether  or  chloroform  is  inhaled  through  the  nose,  a  momentary  rise  of 
arterial  pressure  corresponding  to  an  arrest  of  respiration,  and,  like  it, 
evidently  produced  by  irritation  of  the  peripheral  trigeminal  branches. 

As  was  first  proved  by  the  English  Chloroform  Committee,10  after  the 
first  half-minute  of  the  inhalation  of  chloroform  there  is  a  progressive 
lowering  of  the  arterial  pressure.  This  has  been  confirmed  by  all  ob- 
servers on  the  lower  animals,  and  Blauel88  has  shown  by  tonometrical 
experiments  that  the  same  phenomenon  occurs  in  man.  The  matter  of 
dispute  has  been  as  to  the  cause  of  this  fall, — whether  it  is  of  cardiac  or 
vascular  origin. 

Injected  into  the  jugular  vein,*  chloroform  instantly  arrests  the  heart's  action 
and  destroys  its  muscular  irri lability. f  Even  the  vapor  of  chloroform,  when  locally 
applied  to  the  exposed  heart,  paralyzes  it."  When  artificial  respiration  is  main- 
tained, the  effect  of  chloroform  is  very  apparent."  By  a  very  ingenious  series  of 
experiments,  MacWilliam 1&  has  proved  that  very  early  in  chloroform  anaesthesia 
there  is  a  marked  diminution  of  the  force  of  the  auricular  and  the  ventricular  beats, 
accompanied  by  dilatation  of  the  cardiac  chambers,  due  to  the  direct  influence  of 
the  chloroform.  Again,  as  stated  by  Gaskell  and  Shore,  even  the  tracings  of  the 
Hyderabad  Commission  demonstrate  that  from  the  very  beginning  of  chloroformi- 

*  See  also  MacWilliam's  experiments. 

t  Glover  (Edinb.  Med.  Journ.,  1842),  Gosselin  (Arch.  Gen.,  1848),  Anstie,  and  H.  C. 
Wood. 


ANAESTHETICS.  95 

zation  the  excursions  of  the  heart-beat,  as  shown  on  the  Pick  manometer  in  the 
most  typical  manner,  get  smaller  and  smaller  as  the  pressure  falls.  Indeed,  as 
Gaskell  and  Shore  say,  "  every  one  would  agree  with  the  Commission  that  they 
[the  pulse-waves]  are  of  the  typical  kind  which  would  be  produced  if  direct  weaken- 
ing of  the  heart  were  the  cause  of  the  fall  of  blood-pressure  in  chloroform  adminis- 
tration." Tunnicliffe  and  Rosenheim,39  using  the  method  of  Locke,  found  that  i  to 
25,000  in  the  blood  of  chloroform  notably  affected  the  heart,  and  Schafer  and  Schar- 
lieb,  ibid.,  have  reached  similar  results.  In  the  experiments  of  E.  H.  Embley,40 
made  in  the  method  of  Hering  upon  the  mammalian  heart  isolated  from  nervous 
and  respiratory  influences,  it  was  determined  that  the  heart  is  so  sensitive  to  the 
vapor  of  chloroform  that  0.8  per  cent,  in  the  blood  will  produce  paralysis  in  sixteen 
minutes,  and  with  two  per  cent.,  arrest  occurs  in  one  minute  twenty-five  seconds. 

In  an  elaborate  series  of  experiments,  Sherrington  and  Sowton  (B.  M.  J.  Supp., 
1903,  ii.)  found  that  the  heart  muscle  rapidly  takes  up  chloroform  from  the  blood- 
vessel, the  tension  or  amount  of  the  chloroform  in  the  muscle  depending  not  upon 
the  length  of  time  of  exposure  but  upon  the  percentage  of  chloroform  in  the  fluid 
circulating  in  the  coronary  arteries  ;  it  was  further  determined  that  the  presence  of 
the  chloroform  in  the  muscle  is  accompanied  by  depression  of  function,  and  that 
when  the  percentage  is  great  muscular  paralysis  occurs.  The  important  obser- 
vation was  also  made  that  the  susceptibility  of  the  hearts  of  different  cats  to  chloro- 
form varies.  The  thought  naturally  arises  from  this  research  that  sudden  death 
may  occur  during  chloroform  anaesthesia  from  the  momentary  sudden  increase  of 
the  percentage  of  chloroform  in  the  blood. 

The  concurrent  testimony  of  numerous  investigators  is  so  strong  that 
the  conclusion  cannot  be  escaped  from  that  chloroform  is  a  direct  cardiac  de- 
pressant. This,  however,  does  not  disprove  the  theory  of  vaso-motor  dila- 
tation as  one  of  the  sources  of  arterial  depression  in  chloroform  anaesthesia. 

The  only  experiments  with  which  we  are  acquainted,  to  which  any  weight 
should  be  attached,  as  indicating  that  chloroform  primarily  paralyzes  the  vaso- 
motor  centres,  are  those  published  as  long  ago  as  1874  by  H.  P.  Bowditch  and 
C.  S.  Minot.12  In  these  experiments,  which  were  made  upon  curarized  animals, 
"irritation  of  the  saphena  nerve  caused  a  much  less  marked  rise  of  blood-tension 
than  when  the  anaesthetic  was  not  used.  Sometimes  there  was  absolutely  no  rise 
of  tension  to  be  observed,  while  at  other  times  the  rise  was  from  one-third  to  one- 
half  that  produced  by  the  same  irritation  on  an  animal  not  subjected  to  the  action 
of  chloroform."  Further  compression  of  the  carotid  in  the  chloroformed  animal 
did'not  cause  the  customary  spasm  and  rise  of  arterial  pressure. 

It  must  be  remembered  that  these  experiments  of  Bowditch  and  Minot  were 
made  at  a  time  when  the  importance  of  the  subject  had  not  been  fully  realized  ; 
that  on  the  carotid  but  a  single  experiment  was  made  ;  and  that  there  was  fre- 
quently in  the  experiments  of  Bowditch  and  Minot  a  great  rise  of  pressure  follow- 
ing irritation  of  the  sensitive  nerve,  though  the  rise  was  not  as  great  as  in  the 
normal  dog. 

It  must  also  be  remembered  that  chloroformization  interferes  with  the  functional 
activity  of  the  sensory  side  of  the  nervous  system,  so  that  an  impulse  produced  by 
irritation  of  the  sensitive  nerve  fails  to  reach  the  vaso-motor  centres  in  full  force. 
In  many  of  the  experiments  of  Bowditch  and  Minot,  irritation  of  the  saphenous 
nerve  produced  distinct  rise  of  pressure,  showing  that  the  vaso-motor  centre  was 
not  paralyzed,  though  the  arterial  pressure  had  fallen  very  distinctly :  moreover, 
late  in  chloroform-poisoning  there  is  a  vaso-motor  paralysis,  and  it  may  very  well 
be  that  in  the  single  carotid  experiment  of  Bowditch  and  Minot  the  chloroformiza- 
tion had  been  carried  on  to  the  fullest  extent. 


96  GENERAL    REMEDIES. 

Whilst  undoubtedly  in  advanced  chloroformization  there  is  vascular 
paralysis,  there  seems  to  be  at  present  no  proof  that  this  vascular  paraly- 
sis occurs  as  one  of  the  primary  or  early  symptoms  produced  by  the  drug. 
On  the  other  hand,  there  is  much  evidence  to  show  that  the  first  action 
of  chloroform  is  to  produce  vascular  contraction. 

Sansom  and  Harley  state  that  there  is  a  spasm  of  the  small  vessels,  which  can 
be  readily  seen  to  occur  in  the  web  of  the  frog  during  chloroformization.  Not 
until  the  third  stage  is  reached,  according  to  these  authors,  do  the  vessels  relax 
into  dilatation.  If  these  observations  be  correct,  chloroform  first  stimulates  and 
afterwards  depresses  the  vaso-motor  centres.  In  accordance  with  this  are  the  im- 
portant experiments  of  Gaskell  and  Shore,11  who  find  that  the  local  application  of 
chloroform  to  the  medulla  or  its  injection  into  the  cerebral  artery  produces  an  im- 
mediate rise  of  blood-pressure,  usually  accompanied  by  a  slowing  of  the  heart, 
which  is  followed  by  a  fall  of  pressure  so  soon  as  the  chloroform  is  able  to  diffuse 
itself  throughout  the  circulation.  Gaskell  and  Shore  further  so  connected  the 
carotid  arteries  and  jugular  vein  of  an  animal  (A)  with  the  similar  vessels  of  a 
second  animal  (B)  that  the  brain  of  A  was  fed  exclusively  with  blood  from  B.  It 
is  plain  that  chloroform  given  to  B  would  reach  the  brain  of  A  but  would  not  reach 
the  heart  of  A.  Under  these  circumstances  it  was  found  that  chloroform  adminis- 
tered to  B  produces  rise  of  blood-pressure  in  A.  In  a  second  series  of  experiments 
the  blood-vessels  of  A  were  so  connected  with  those  of  B  that  when  chloroform 
was  administered  to  B  it  reached  the  heart  of  A  and  all  other  portions  of  the  body 
except  the  brain.  When  this  was  the  case,  chloroform  given  to  B  produced  an 
immediate  fall  of  pressure  in  A  without  there  having  been  any  rise.  In  other 
words,  when  chloroform  reached  the  vaso-motor  centres  and  not  the  heart,  it  caused 
rise  of  arterial  pressure  ;  when  it  reached  the  heart  and  not  the  vaso-motor  centres, 
it  caused  fall  of  pressure.  In  accord  with  the  results  of  Gaskell  and  Shore,  it  has 
been  found  by  Embley  that  the  local  application  of  chloroform  to  the  vaso-motor 
centres  produces  rise  of  the  arterial  pressure,  which  is  presumably  due  to  stimu- 
lation of  the  vaso-motor  centres.  In  common  with  other  observers,  Embley  found 
that  later  in  the  chloroformization  there  is  a  vascular  paralysis  which  he  believes 
to  be  due  to  a  direct  action  of  the  chloroform  on  the  muscles  of  the  heart  vessels. 

Putting  all  the  evidence  together,  it  seems  to  us  to  have  been  demon- 
strated by  physiologists,  first,  that  chloroform  is  a  direct  depressant  and 
paralyzant  to  the  heart-muscle  or  its  contained  ganglia  /*  second,  that 
the  fall  of  blood-pressure  which  occurs  in  chloroformization  is  at  first  due 
to  this  direct  depression  of  the  heart,  but  subsequently  to  coincident  vascular 
and  cardiac  faihire. 

Respiration. — So  soon  as  psychical  excitement  has  passed  off,  or,  at 
first,  if  there  be  no  such  excitement,  the  respirations  may  be  rendered 
slower  by  chloroform,  but  after  a  time  they  are  generally  quickened,  and 
as  the  inhalation  is  persisted  in  they  become  more  and  more  shallow, 

*  The  work  of  the  Hyderabad  Commission  has  become  so  celebrated  that  it  hardly 
seems  necessary  to  explain  that  they  reached  with  extreme  positiveness  the  conclusion 
that  chloroform  kills  purely  through  the  respiration,  and  that  it  is  a  perfectly  safe  anaes- 
thetic. Rather  strangely,  they  based  their  belief  that  the  fall  of  Wood-pressure  under 
chloroform  is  not  due  to  weakening  of  the  heart  chiefly  upon  certain  atypical  tracings 
which  they  obtained.  The  publication  of  these  tracings  shows,  in  the  language  of  Gas- 
kell and  Shore,  "  that  these  cases  afford  no  proof  whatever  that  the  heart's  action  is  not 
impaired  by  the  action  of  chloroform." 


ANAESTHETICS.  97 

irregular,  and  distant,  and  finally  cease.  In  1870  Paul  Bert16  asserted 
that  during  chloroformization  there  is  more  than  the  normal  percentage  of 
oxygen  in  the  blood,  but  in  1885  he  affirmed  that  there  was  less  than  the 
normal  percentage. "  There  does  not  seem  to  be  much  doubt  that  the 
results  of  L.  G.  de  Saint-Martin18  are  correct, — namely,  that  whilst 
(probably  on  account  of  excessive  respiration  from  excitement)  in  the 
beginning  of  chloroformization  there  is  sometimes  hyperoxygenation  of 
the  blood,  the  rule  during  full  anaesthesia  is  decrease  of  the  oxygen  of  the 
blood  with  increase  of  the  carbonic  acid. 

According  to  the  work  of  E.  H.  Embley,  chloroform  is  a  very  active 
vagus  stimulant,  raising  the  excitability  of  the  vagus  centrically,  and  it 
has  been  urged  that  sudden  death  occurs  during  chloroformization  from 
inhibitory  cardiac  arrest.  Before,  however,  this  conclusion  can  be  con- 
sidered established  further  experiments  seem  necessary. 

Death  has  frequently  occurred  from  chloroform  after  the  inhalation  of  a  few 
whiffs  of  vapor.  The  theory  was  suggested  many  years  ago  that  the  cause  of  car- 
diac arrest  is  irritation  of  the  respiratory  mucous  membranes,  producing  a  fatal 
cardiac  inhibition  ;  a  conclusion  which  reached  confirmation  in  the  observations  of 
Vulpian,  that  the  heart  under  the  influence  of  chloral,  a  substance  closely  allied  to 
chloroform,  is  equally  sensitive  to  slight  inhibitory  impulses.  Out  of  this  has  grown 
the  practical  suggestion  that  the  surgeon  should  wait  until  complete  chloroform- 
ization, lest  the  irritation  produced  by  the  first  cut  should  produce  a  momentary 
excessive  inhibition.  In  a  number  of  experiments,  however,  made  by  H.  C.  Wood, 
it  was  found  that  the  application  of  chloroform  to  the  upper  respiratory  passages  of 
the  dog  would  distinctly  inhibit  but  never  arrest  cardiac  movement.  Embley 
believes  that  these  chloroform  deaths  are  due  to  an  excessive  excitation  of  the 
inhibitory  centric  apparatus,  and  are  therefore  the  outcome  of  an  intense  inhibition 
exercised  upon  the  heart,  whose  spontaneous  excitability  is  diminished  by  the 
chloroform  vapor.  He  bases  this  conclusion  upon  his  experimental  observations, 
that  when  inhalations  of  chloroform  of  the  strength  of  two  per  cent,  and  upward 
have  been  given  and  the  blood-pressure  has  fallen,  stimulation  of  the  vagi  with  the 
faradic  current  fatally  inhibits  the  heart.  It  should  be  noted,  however,  that  if  this 
observation  be  correct  it  proves  not  centric  but  peripheral  stimulation  ;  or  what  is 
equally  probable,  diminished  power  of  the  heart-muscle  to  resist  inhibitory  impulses. 

The  curious  observation  was  also  made  by  Embley  that  when  the  breathed  air 
contained  not  more  than  five  per  cent,  of  chloroform,  the  vagus  excitability  was 
slightly  depressed.  It  seems  to  us  evident  that  at  present  the  question  as  to  exactly 
what  rdle  inhibition  plays  in  chloroform  deaths  has  not  been  finally  answered. 

Blood. — As  was  first  demonstrated  by  Harley,19  five  per  cent,  of  chloro- 
form in  the  blood  destroys  the  red  corpuscle  with  a  final  deposition  of 
crystals  of  oxyhaemoglobin. 

Boettcher20  was,  we  believe,  the  first  to  study  these  changes  closely.  The  first 
alteration  noticeable  in  the  red  blood-disks  is  a  diminution  of  their  size,  which  A. 
Schmidt  and  F.  Schweiger-Seidel 21  assert  to  be  due  to  contraction,  because  when 
blood  is  treated  with  water  until  the  red  globules  disappear,  and  carbonic  acid  gas 
is  passed  through  the  liquid  until  they  reappear,  on  the  addition  of  chloroform  the 
sharply  contoured  bodies  will  be  seen  to  undergo  marked  contraction.  As  was 
first  shown  by  Boettcher  and  confirmed  by  Schmidt  and  Schweiger-Seidel,  chloro- 

7 


98  GENERAL  REMEDIES. 

form  alone  produces  no  other  alteration  than  contraction  in  the  red  blood-disks. 
If,  however,  air  be  admitted  to  blood  containing  chloroform,  the  corpuscles  rapidly 
disappear,  dissolving  the  serum,  out  of  which,  after  a  time,  oxyhaemoglobin  crys- 
tallizes. Both  of  the  authorities  quoted  believe  that  the  latter  changes  are  due  to 
oxidation.  Boettcher  states  that  chloroform-vapor  mixed  with  air  converts  enough 
of  the  oxygen  of  the  latter  into  ozone  to  react  with  iodized  starch-paper ;  and 
Schmidt  and  Schweiger-Seidel  have  found  that  an  excess  of  carbonic  acid  in  the 
blood  interferes  with  the  changes  caused  by  chloroform.  The  facts  just  noted  indi- 
cate that  the  blood  changes  are  the  result  of  simple  oxidation,  but  the  studies  of  F. 
Kriiger 41  show  that  chloroform,  at  least  outside  of  the  body,  produces  a  series  of 
chemical  changes  in  the  haemoglobin. 

How  far,  during  ordinary  narcosis,  chloroform  causes  changes  in  the 
blood  is  uncertain.  A  very  sensitive  test  of  the  destruction  of  the  red 
disks  in  the  body  is  found  in  the  production  of  icterus  ;  icterus  following 
chloroformization  is  very  rare,  but  the  assertion  of  Frerichs  that  it  does 
occur  is  correct.  Bernstein23  and  Leyden24  have  found  traces  of  bile- 
pigment  in  the  human  urine  after  chloroform-narcosis  ;  whilst  Nothnagel 18 
detected  bile  coloring-matter'  in  the  urine  of  rabbits  after  subcutaneous 
injection  of  chloroform  or  ether.  Husemann 26  intimates,  on  what  author- 
ity we  do  not  know,  that  after  anaesthesia  bile-acids  (the  precursors  of 
icterus)  appear  in  the  urine  ;  but  Kappeler,"  in  twenty-five  cases  of  chlo- 
roform-narcosis, was  not  able  to  obtain  a  trace  of  biliary  coloring-matter. 
Sokolovski M  asserts  that  the  first  few  hours  after  chloroformization  there 
is  a  decrease  of  the  immature  white  blood-corpuscles,  with  an  increase  of 
the  mature  white  blood-corpuscles,  followed  by  gradual  return  to  normal. 

After  death  during  chloroform  anaesthesia  the  presence  of  gas  has  been  fre- 
quently noticed  in  the  blood-vessels  and  in  the  heart.  Contrary  to  the  conclusions 
reached  by  various  authors,  Kappeler "  has  shown  that  usually,  if  not  always,  the 
gas  has  been  liberated  by  putrefactive  changes  occurring  after  death.  The  state- 
ment of  Pirogoff,  that  he  has  witnessed  the  throwing  out  of  gas  from  the  blood 
during  life,  has  never  been  confirmed,  but  it  is  possible  that  the  chloroform  may 
have  some  influence  upon  the  capacity  of  the  blood  for  holding  gases. 

General  Nutrition.  — That  chloroform  affects  the  general  nutrition  of 
the  body  is  demonstrated  by  the  wide-spread  fatty  degeneration  which 
sometimes  follows  long-continued  narcosis  produced  by  it  (see  page 
116),  as  well  as  by  the  observations  of  Strassmann,29  who  found  that  a 
pronounced  increase  of  the  nitrogenous  elimination  follows  chloroform- 
narcosis,  an  increase  which  would  seem  to  be  directly  due  to  the  anaes- 
thetic, since  Salkowski  demonstrated  that  chloroform-water  given  to  dogs 
distinctly  increases  the  destruction  of  nitrogenous  substances  in  the  body 
without  producing  narcosis.* 

According  to  the  researches  of  Strassmann80  and  of  Salkowski,81 
chloroform  is  an  active  antiseptic  and  germicide.  Both  Salkowski  and 

*  J.  Petruechky  (Deutsche  Med.  Wochensch.,  1891,  xvii.)  has  noticed  that  after  death 
from  chloroform  the  intercellular  juices  become  rapidly  acid,  and  he  has  found  that  this 
is  not  peculiar  to  chloroform,  but  takes  place  also  after  death  from  ether,  arsenic,  and 
other  poisons. 


ANESTHETICS.  99 

A.  Bertels S2  find  that  the  drug  also  checks  the  action  of  pepsin  and  other 
unformed  ferments. 

THERAPEUTICS. — For  a  discussion  of  the  use  of  chloroform  as  an 
anaesthetic,  see  page  103. 

When  administered  by  the  mouth  in  sufficient  quantity,  chloroform 
produces  symptoms  similar  to,  but  much  more  permanent  than,  those 
which  it  causes  when  inhaled.  It  is,  however,  very  rarely,  if  ever,  used 
in  this  way  for  its  constitutional  effect,  but  is  sometimes  of  advantage  in 
severe  neuralgia.  When  for  any  reason  quinine  cannot  be  administered 
in  an  ague,  a  sufficient  dose  of  chloroform  (fgss  to  fgi)  to  produce  a 
mild  narcosis,  just  before  the  expected  time  for  the  recurrence  of  the  chill, 
will  often  abort  it.  Chloroform  by  the  mouth  has  been  also  highly 
recommended  as  a  vermifuge  in  cases  of  tape-worm,  but  is  of  doubtful 
value. 

When  chloroform  is  taken  into  the  stomach,  a  considerable  portion  of 
it  is,  without  doubt,  evaporated,  so  that  the  intestinal  canal  becomes  filled 
with  the  vapor.  Chloroform,  therefore,  when  so  placed  exerts  both  a 
local  anodyne  and  a  stimulant  carminative  action.  For  this  reason  it  is 
valuable  in  ordinary  colic  and  in  colica  pictonum. 

Externally,  as  a  rubefacient  and  anodyne,  chloroform  is  very  largely 
combined  with  other  substances  into  liniments,  which  are  especially  useful 
in  cases  of  chronic  neuralgic  or  rheumatic  pains. 

Poisoning  has  been  produced  by  the  swallowing  of  chloroform.  The 
symptoms  induced  have  been  stupor,  with  contracted,  or,  in  later  stages, 
dilated,  pupils,  and  a  stertorous  respiration,  which  finally  becomes  very 
irregular,  shallow,  and  often  distant.  The  amount  necessary  to  destroy 
life  probably  varies  greatly,  but,  according  to  L.  Lewin,  a  single  drachm 
has  produced  death.  In  some  cases M  the  fatal  result  has  occurred  from 
secondary  gastritis  many  days  after  taking  the  medicine  ;  and  not  rarely 
violent  gastritis  with  jaundice  apparently  from  inflammation  of  the  gall- 
ducts  has  been  produced.  Recovery  has  occurred  after  the  ingestion  of 
three  ounces  without  vomiting  ; M  also  five  ounces.  The  treatment  consists 
in  the  use  of  the  stomach-pump  and  of  the  various  ordinary  methods  of 
arousing  a  narcotized  patient,  especially  the  alternate  cold  and  hot  douche, 
artificial  respiration,  and  the  very  cautious  use  of  diffusible  stimuli  if  re- 
quired. Death  may  occur  during  the  narcosis,  or  the  patient  may  sur- 
vive this  and  perish  from  inflammation  of  the  trachea,  oesophagus,  and 
stomach,  caused  by  the  local  action  of  the  chloroform. 

The  recognition  of  chloroform  as  the  probable  cause  of  any  given 
death  cannot  be  based  upon  the  post-mortem  appearances.  Indeed,  the 
latter  are  of  no  value  in  deciding  such  a  question.  The  anaesthetic  may, 
however,  be  recovered  by  distillation  of  the  lungs  and  blood  within  a  cer- 
tain period  of  time  after  death.  As  to  the  length  of  this  time,  so  far  as 
we  are  aware,  no  investigations  have  been  made. 

Criminal  Relations. — Experiments  made  at  the  Philadelphia  Hospital 
and  confirmed  by  Dolbeau M  and  by  Paugh "  have  proved  that  persons 


ioo  GENERAL  REMEDIES. 

sound  asleep  may  be  chloroformed  without  being  awakened.  Anaesthesia 
cannot,  however,  be  produced  in  any  one  partially  awake,  or  even  sleeping 
lightly,  without  his  or  her  knowledge. 

.Quite  a  number  of  professional  men  have  been  accused,  and  some 
convicted  on  the  charge,  of  committing  rape  on  females  in  whom  they 
had  induced  anaesthesia.  No  doubt  the  women  believed  that  they  had 
been  violated  ;  but  it  is  certain  that  in  many  of  the  cases  they  mistook  for 
the  real  act  the  subjective  erotic  sensations  induced  by  the  chloroform  or 
ether.  The  valuelessness  of  the  testimony  of  persons  as  to  occurrences 
during  the  time  of  their  intoxication  with  anaesthetics  should  be  recognized 
in  law  as  a  governing  principle  of  evidence. 

ADMINISTRATION.  —  The  internal  dose  of  chloroform  is  from  fifteen 
drops  to  a  fluidrachm  (0.9-3.7  C.c.  ).  The  deep  injection  of  half  a 
drachm  of  chloroform  has  been  recommended  very  strenuously  by 
Bartholow  in  obstinate  neuralgia,  and  has  found  some  favor  in  France.  ss 
In  the  only  case  in  which  we  have  tried  it,  one  of  trigeminal  neuralgia,  the 
local  symptoms  caused  by  it  were  so  severe  as  to  imperil  the  life  of  the 
patient.  The  U.  S.  Pharmacopoeia  recognizes  a  spirit  (SriRiTUS  CHLO- 
ROFORMI  —  six  per  cent.,  U.  S.  ),  dose,  one  to  two  fluidrachms  (3.7-7.5 
C.c.)  ;  an  emulsion  (EMULSUM  CHLOROFORMI  —  four  per  cent.,  U.  S.  )  ; 
a  liniment  (LINIMENTUM  CHLOROFORMI  —  thirty  per  cent.,  U.  S.  )  ;  and 
a  water  (AQUA  CHLOROFORMI,  U.  S.),  dose,  four  fluidrachms  (16  C.c.). 


CHLORIDUM.  U.  S.  —  Ethyl  chloride  is  a  colorless,  ex- 
tremely volatile  liquid  of  specific  gravity  (at  o°  C.  )  of  0.918,  boiling  at 
12.5°  C.  On  account  of  its  volatility,  it  has  been  much  used  under 
various  names  to  produce  local  anaesthesia  by  freezing.  Recently  ethyl 
chloride  has  been  employed  as  a  general  anaesthetic.  It  acts  very  rapidly 
and  recovery  occurs  abruptly  on  removal  of  the  drug.  Ware  has  col- 
lected 1  1  ,  207  cases  of  its  use,  with  one  death.  Other  deaths  have  been 
reported  by  Hacker,  by  Allen5  and  by  Gifford6.  It  was  partially  studied 
physiologically  in  1892  by  Wood  and  Cerna,1  who  found  that  it  produced 
an  amount  of  circulatory  depression  disproportionate  to  its  anaesthetic 
properties,  and  was  so  fugacious  in  its  action  as  to  be  scarcely  fit  for  use 
as  a  general  anaesthetic.  In  Lebet's2  experiments  upon  rabbits,  the  intra- 
venous injection  was  found  to  produce  great  circulatory  depression  ;  on 
the  isolated  frog's  heart  the  twenty-five  per  cent,  solution  of  ethyl  chloride 
appeared  to  act  as  an  irritant  rather  than  a  depressant.  Moreover, 
Malherbe  and  Roubinovitch3  have  proven  with  Retain'  s  sphygmomano- 
meter  that  in  man  the  arterial  tension  is  almost  always  clearly  lessened. 
Ware4  found  the  drug  best  administered  by  means  of  modified  nitrous 
oxide  inhaler. 

ETHYL  BROMIDE  is  a  colorless,  very  volatile,  very  fluid  liquid,  having 
the  specific  gravity  1.49,  of  a  sweet,  chloroform-like  smell  ;  not  readily 
inflammable  ;  insoluble  in  water,  but  mixing  with  ether,  chloroform,  fat, 


ANAESTHETICS.  101 

and  ethereal  oils  in  all  proportions.  It  does  not  solidify  at  32°  F.  Any 
preparation  of  it  which  has  color,  or  seems  irritating,  or  has  a  disagreeable 
smell,  is  unfit  for  medicinal  use.  It  must  clearly  be  separated  by  the 
practitioner  from  ethylene  bromide,  which  has  a  specific  gravity  2.16,  and 
solidifies  at  32°  F.  into  a  crystalline  mass.  Scherbatscheff  has  collected 
four  deaths  produced  by  the  substitution  of  ethylene  bromide  for  ethyl 
bromide.1  Ethyl  bromide  degenerates  under  the  influence  of  light  and 
air,  and  should,  therefore,  always  be  kept  in  small  bottles  of  dark  glass, 
closely  corked. 

Proposed  as  an  anaesthetic  in  1849,  exploited  by  Rabuteau  in  France 
and  by  L.  Turnbull  in  the  United  States  in  1876-77,  ethyl  bromide  has 
been  used  to  a  considerable  extent  as  an  anaesthetic.  Its  influence  usually 
manifests  itself  in  a  few  seconds  and  lasts  not  longer  than  three  minutes 
after  the  removal  of  the  inhaler.  Various  observers  state  that  sensibility 
is  not  rarely  lost  before  consciousness,  and  Montgomery  has  especially 
noted  that  during  parturition  ethyl  bromide  will  do  away  with  most  of  the 
suffering  without  arresting  the  pains  or  producing  complete  relaxation  of 
the  muscles  ;  indeed,  it  appears  to  be  common  for  the  general  muscular 
tonus  to  be  greatly  increased  by  it.  According  to  John  H.  Brinton, 
muscular  excitement,  as  shown  by  rigidity,  local  spasms,  and  even  general 
tetanus  with  opisthotonos,  occurs  so  frequently  as  seriously  to  interfere 
with  the  anaesthetic  use  of  the  drug,  especially  as  this  condition  during  a 
surgical  operation  is  attended  by  great  increase  of  hemorrhage.2  During 
narcosis  the  corneal  and  pupillary  reflexes  are  usually  preserved,  and  the 
eyes  are  sometimes  wide  open  and  crossed  from  contractions  of  their 
muscles  (Gilles8). 

The  physiological  action  of  ethyl  bromide  has  been  partially  studied 
by  Schneider,  Thornton  and  Maxwell,4  Abonyi,5  H.  C.  Wood,14  Ginsburg," 
and  S.  W.  Cole 16  with  results  apparently  not  altogether  concordant.  * 

All  observers  agree  that  in  the  narcosis  the  arterial  pressure  finally 
falls,  but  Ginsburg  and  Schneider  note  that  this  fall  is  preceded  by  a  rise 
in  the  arterial  pressure,  which  appears  not  to  have  been  present  in  the 
experiments  of  Thornton  and  Maxwell  or  of  H.  C.  Wood.  Ginsburg 
believes  that  the  fall  of  arterial  pressure  is  due  to  a  paralysis  of  the  vaso- 
motor  centres,  and  Abonyi  was  not  able  to  detect  any  alterations  in  the 
beat  of  the  excised  heart  of  the  frog  when  narcosis  was  produced.  The 
recent  work  of  Tcherbacheff,  who  found  that  ethyl  bromide  causes  death 
from  cardiac  paralysis  with  or  without  pulmonary  oedema,  accords,  how- 
ever, with  the  early  conclusions  of  H.  C.  Wood  that  ethyl  bromide  acts 
upon  the  heart  in  a  manner  similar  to  chloroform. 

The  respiratory  action  of  ethyl  bromide  has  not  been  carefully  studied. 
It  probably  is  a  centric  depressant.  Ch.  Livon  finds,  from  analysis  of  the 
gases  of  the  blood,  that  during  the  anaesthesia  produced  by  the  ethyl 

*  We  are  not  aware  that  the  purity  of  the  ethyl  bromide  used  has  been  proved  by  any 
of  the  experimenters.  Linguistic  difficulties  in  regard  to  the  Slavonic  papers  have  com. 
pelled  us  to  rely  upon  abstracts. 


102  GENERAL  REMEDIES. 

bromide  there  is  lessening  of  the  carbonic  acid  with  augmentation  of  the 
oxygen. 

In  the  absence  of  conclusive  statistics,  ethyl  bromide  appears  to  be  at 
least  as  immediately  dangerous  as  chloroform,  and  distinctly  more  so  in 
its  secondary  results.  It  is  true  that  Gilles  claims  that  with  a  commer- 
cially pure  bromide  twenty  thousand  successive  administrations  of  ethyl 
bromide  in  Germany  had  been  without  death,  and  that  the  fatal  results 
have  been  due  to  impurity  in  the  drug.  This  certainly  does  not  apply  to 
the  deaths  recorded  by  A.  Gleich7  and  Suarez  de  Mendoza.8 

When  a  very  brief  anaesthetic  effect  is  desired,  ethyl  bromide  may  be 
used  as  probably  no  more  dangerous  than  chloroform  ;  but  the  fugacious- 
ness  of  its  action  and  the  muscular  excitement  which  it  causes  forbid  its 
general  employment  in  major  surgery,  whilst  the  recent  developments  of 
local  anaesthesia  greatly  lessen  the  field  of  its  utility  in  minor  operations. 
The  ease  with  which  ethyl  bromide  undergoes  change  offers  a  serious  dif- 
ficulty to  its  use.  Certainly  the  surgeon  should  see  that  the  individual 
specimen  employed  has  every  appearance  of  being  pure. 

Hennicke  has  proved  that  ethyl  bromide  undergoes  decomposition  in 
the  system  with  the  liberation  of  bromine  compounds,  and  as  bromine  is 
much  more  poisonous  than  chlorine,  it  is  to  be,  a  priori,  expected  that 
ethyl  bromide  will  be  more  apt  to  produce  wide-spread  organic  changes 
in  the  general  tissues  than  is  the  older  anaesthetic.  In  accordance  with 
this,  cases  have  been  reported  by  Reich9  and  by  Flatten,10  in  which  the 
inhalation  of  the  bromide  has  been  followed  by  persistent  vomiting,  gen- 
eral weakness,  and  death  (in  from  one  to  seven  days),  and  in  which  the 
liver,  the  kidneys,  and  the  heart-muscles  were  found  to  have  undergone 
acute  fatty  degeneration. 

Methyl  bromide. — Certain  other  bromide  compounds  have  been  suggested  as 
anaesthetics.  Methyl  bromide  seems  to  be  very  poisonous,  especially  on  account 
of  its  prolonged  action,  probably  due  to  slow  elimination.  For  nineteen  cases  of 
poisoning  by  it,  see  A.  Jaquet  (Deutsches  Archivf.  klin.  Med.,  vol.  Ixxi. ). 

PENTAL — TRIMETHYLETHYLENE. — This  is  a  colorless,  highly  inflammable 
liquid,  boiling  at  100°  F.,  originally  proposed  by  W.  Lombardino  as  a  practical 
anaesthetic.  It  acts  with  great  promptness  without  marked  disagreeable  symptoms, 
producing  a  short  narcosis,  which  is,  however,  longer  than  that  caused  by  ethyl 
bromide.  In  three  hundred  narcoses  by  it,  P.  Philipp  1  failed  to  find  any  depression 
of  the  heart  or  severe  asphyxia.  Pental  is  also  commended  by  Kleindienst,  who, 
however,  noted  that  very  frequently  three  or  four  days  after  the  narcosis  there  was 
abundant  albuminuria,  and  not  rarely  haematuria  or  haemoglobinuria  occurs.  In  a 
study  of  the  drug  by  David  Cerna,2  anaesthesia  caused  by  it  in  the  dog  was  found  to 
be  accompanied  always  by  marked  fall  of  the  arterial  pressure,  and  the  conclusion 
was  reached  that  the  remedy  depresses  the  heart.  The  alleged  action  of  pental 
upon  the  kidneys,  if  it  be  true,  negatives  its  use  as  a  practical  anaesthetic.  From 
the  statistics  of  Gurlt,*  it  is  the  most  dangerous  of  all  the  anaesthetics,  there  having 
been  three  deaths  in  the  six  hundred  reported  narcoses. 

METHYLENE  BICHLORIDE  was  introduced  to  the  notice  of  the  profession  by  B. 
W.  Richardson,1  as  an  anaesthetic  similar  to,  but  more  pleasant  and  possibly  safer 


ANESTHETICS.  103 

than,  chloroform,  and  has  been  rather  extensively  used  in  London.  It  has  never 
been  largely  employed  in  this  country.  There  is  no  way  of  knowing  how  many 
times  it  has  been  administered,  but  nine  cases  of  death  from  its  use  are  recorded.2 
The  detailed  phenomena  in  these  cases  indicate  that,  like  chloroform,  methylene 
bichloride  kills  by  paralyzing  the  heart.  It  is  not  probable  that  it  will  ever  come 
into  general  use  as  an  anaesthetic. 

PRACTICAL  ANAESTHESIA.* — Although  various  substances  have  from 
time  to  time  been  used  as  anaesthetics,  the  surgical  profession  has  prac- 
tically settled  down  to  the  employment  of  either  ether  or  chloroform,  and 
experience  seems  to  show  that  there  are  no  other  known  agents  which  act 
as  well  as  do  these  two  liquids.  The  question  as  to  which  of  them  should 
be  preferred  is  a  vital  one,  as  are  also  the  questions  how  to  recognize  and 
how  to  treat  the  accidents  which  occur  during  anaesthesia.  It  must  be  in 
the  beginning  granted  that  the  production  of  anaesthesia  is  always  at- 
tended by  a  danger  which,  though  small,  is  positive,  and  that  fatal  acci- 
dents will  always  occur  from  time  to  time.  There  are  few  things  in  medical 
literature  more  tiresome  than  the  arrogant  assertions  of  various  surgeons 
that  they  have  never  had  a  fatal  accident  from  chloroform  or  ether  because 
of  the  special  methods  by  which  they  have  used  them.  May  their  conceit 
die  with  them.  All  that  a  surgeon  can  hope  for  is  to  reduce  the  number 
of  these  accidents  to  a  minimum. 

In  selecting  the  agent,  convenience  of  administration  both  to  the  sur- 
geon and  to  the  patient  is,  of  course,  of  importance  ;  but  we  hold  that 
such  advantage  ought  not  to  be  pitted  against  danger  of  fatal  results. 
For  reasons  which  were  given  in  H.  C.  Wood's  address  before  the  Berlin 
International  Congress,  it  is  doubtful  whether  half  the  deaths  produced 
by  anaesthetics  are  reported,  but  thousands  have  been  recorded.  The 
ratio  of  deaths  to  inhalations  for  chloroform  is  given  by  Lyman  as  i  in 
5860  ;  by  Richardson  as  i  in  2500  to  3000  (see  also  Coats,1)  ;  whilst 
Andrews  records  it  for  ether  as  i  in  23,204,  and  Lyman  as  i  in  16,542. 
In  nearly  one  million  of  inhalations  (George  M.  Gould2),  the  mortality 
was,  with  chloroform,  i  in  3749  ;  ether,  i  in  16,675.  Garree3  gives  the 
deaths  in  three  hundred  and  fifty  thousand  cases  of  recent  inhalation  of 
ether  as  i  in  14,000.  Gurlt*  in  over  three  hundred  and  thirty  thousand 
cases  gets  the  mortality  for  chloroform  as  i  in  2075  ;  ether,  i  in  5112  ; 
chloroform  and  ether  mixed,  i  in  7613  ;  A.  C.  E. ,  i  in  3370;  ethyl 
bromide,  i  in  5396^  These  statistics  are,  taken  together,  so  enormous 

*  From  time  to  time  various  surgeons  have  essayed  to  assist  in  the  production  and 
prolongation  of  anaesthesia  by  the  use  of  narcotic  alkaloids.  Hypodermic  injections  of 
morphine  given  half  an  hour  before  the  inhalation  of  the  drug  have  been  much  employed, 
but  it  is  doubtful  whether  they  are  of  real  advantage.  In  1900,  Schneiderlin  proposed  the 
substitution  of  scopolamine-morphine  narcosis  for  ordinary  surgical  anaesthesia  and  his 
method  has  found  some  following  (see  p.  189). 

f  Although  not  able  to  give  definite  statistics  upon  the  fact,  we  are  strongly  inclined 
to  believe  that  deaths  from  anaesthesia,  and  especially  from  ether,  are  proportionately 
more  frequent  in  Europe  than  in  America.  If  this  be  so,  one  reason,  it  seems  to  us,  is 
to  be  looked  for  in  the  use  of  the  Clover  and  other  forms  of  closed  inhalers,  with  which 
the  anaesthesia  produced  is  to  a  greater  or  less  extent  due  to  mechanical  asphyxiation. 


io4  GENERAL  REMEDIES. 

in  extent  and  so  concordant  that  it  must  be  considered  established  that 
the  ratio  of  deaths  from  chloroform  is  about  four  times  greater  than  that 
from  ether. 

The  assertion  that  the  inhalation  of  chloroform  is  less  dangerous  in 
tropical  than  in  temperate  climates  has  been  made  so  frequently  and  so 
earnestly  by  various  surgeons  practising  in  hot  countries,  and  is  seemingly 
so  sustained  by  statistics,  that  it  is  probably  correct.  It  has  received  a 
curious  confirmation  from  a  study  of  reported  deaths  from  chloroform  by 
Thomas  R.  Evans,5  which  appears  to  show  that  most  of  these  deaths  have 
occurred  during  the  cold  seasons  of  the  year.  It  is  entirely  possible  that 
the  increased  volatility  of  chloroform  at  high  temperature  facilitates  its 
elimination  from  the  body  and  thereby  lessens  the  dangers  of  its  use. 

The  advantages  of  chloroform  over  ether  are — that  it  is  less  disagree- 
able to  the  patient,  produces  less  excitement,  more  speedily  reduces  the 
subject  to  insensibility,  and  is  less  apt  to  cause  excessive  after-nausea  and 
vomiting.  These  advantages  do  not  at  all  counterbalance  the  great  danger 
to  life,  and  we  believe  that  the  surgeon  is  not  justified  in  using  chloroform 
unless  under  certain  circumstances  and  for  certain  definite  reasons. 

Moreover,  we  believe  that  many  of  the  so-called  disadvantages  of  ether 
can  be  overcome  by  a  little  care.  If  the  stomach  be  empty,  the  after- 
nausea  will  rarely  be  severe,  and  when  the  ether  is  properly  given  with  an 
Allis  inhaler,  the  average  time  required  for  the  production  of  complete 
insensibility  is  eight  minutes,  and  the  sense  of  suffocation  and  the  symp- 
toms of  excitement  are  rarely  pronounced. 

A  study  of  the  reasons  of  the  great  fatality  of  chloroformization  leads 
to  a  study  of  the  methods  by  which  chloroform  and  ether  produce  death. 
The  earlier  teaching  of  H.  C.  Wood  was,  in  accordance  with  the  general 
professional  belief,  "  First,  that  although  ether  in  moderate  doses  acts  as 
a  stimulant  to  the  circulation,  yet,  in  overwhelming  amount,  it  is  capable 
of  depressing  the  heart,  but  that  such  depression  of  the  heart  is  always 
less  than  the  depression  of  the  respiration  ;  secondly,  that  chloroform 
may  produce  death  by  paralysis  of  the  respiratory  centre,  or  by  a  simul- 
taneous arrest  of  respiration  and  circulation,  but  that  primary  paralysis 
of  the  heart  may  occur,  and  is  especially  prone  to  do  so  when  the  chloro- 
form vapor  has  been  given  in  concentrated  form. ' ' 

These  teachings  have  been  very  strongly  combated  by  the  so-called 
Hyderabad  Commission,  led  by  Lauder  Brunton,  of  London,  who,  as 
the  result  of  four  hundred  and  fifty  experiments  made  upon  the  pariah 

Some  years  since  a  method  of  rapid  etherization,  in  which  the  ether  was  put  into  a  gallon 
jar  and  the  patient  forced  to  breathe  in  and  out  of  the  jar,  was  tried  by  Agnew  in  the 
University  Hospital.  Anaesthesia  was  produced  almost  at  once  with  very  little  excite- 
ment, but  in  a  very  brief  period  the  Clinic  nearly  lost  two  patients  from  anaesthesia,  and 
the  method  fell  at  once  into  desuetude.  It  was  really  a  plan  of  asphyxiation  rather  than 
of  etherization.  The  Rolh-Drager  inhaler  is  an  apparatus  invented  for  the  purpose  of 
giving  a  mixture  of  chloroform  with  oxygen.  It  is  claimed  by  Roth  that  under  these  cir- 
cumstances the  chloroform  remains  unchanged,  although  Ernst  Falk  believed  that  his 
chemical  studies  have  demonstrated  that  after  twenty  minutes  of  narcosis  there  is  a  dis- 
tinct decomposition  of  the  chloroform  (D.  M.  W.,  1902,  xxviii.,  and  1903,  xxix.). 


ANESTHETICS.  105 

dogs  of  India,  came  to  the  absolute  conclusion  that  chloroform  never  kills 
by  causing  sudden  stoppage  of  the  heart.  There  is  no  space  in  the 
present  volume  to  go  over  in  detail  the  evidences  which  were  brought  for- 
ward by  H.  C.  Wood  in  his  Berlin  address.  It  was,  however,  we  think, 
definitely  proved  that  the  clinical  and  experimental  facts  are  accordant, 
and  ' '  that  chloroform  acts  much  more  promptly  and  much  more  power- 
fully than  does  ether,  both  upon  the  respiratory  centres  and  the  heart  ; 
that  the  action  of  chloroform  is  much  more  persistent  and  permanent  than 
is  that  of  ether  ;  that  chloroform  is  capable  of  causing  death  either  by 
primarily  arresting  the  respiration  or  by  primarily  stopping  the  heart, 
but  that  commonly  both  respiratory  and  cardiac  functions  are  abolished  at 
or  about  the  same  time  ;  that  ether  usually  acts  very  much  more  power- 
fully upon  the  respiration  than  upon  the  circulation,  but  that  occasionally, 
and  especially  when  the  heart  is  feeble,  ether  is  capable  of  acting  as  a 
cardiac  paralyzant  and  may  produce  death  by  cardiac  arrest  at  a  time 
when  the  respirations  are  fully  maintained."  These  conclusions,  which 
were  based  upon  a  thorough  examination  of  clinical  records  and  a  very 
large  number  of  experiments  performed  in  the  laboratory,  have  since 
been  confirmed  by  John  A.  MacWilliam,6  who  has  recorded  cases  of 
death  in  the  lower  animals  from  chloroform,  in  which  there  was  primary 
collapse  of  the  heart  ;  and  by  the  studies  of  the  Lancet  Commission,7 
which  found  that  out  of  three  hundred  and  fifty-seven  deaths  caused  by 
chloroform,  whose  records  it  had  examined,  the  fatal  result  was  caused 
by  cardiac  failure  two  hundred  and  twenty-seven  times,  by  respiratory 
failure  eighty  times,  and  by  simultaneous  failure  of  the  two  functions 
seventy-seven  times.* 

MacWilliam  also  found  that  in  the  dog  cardiac  weakness  and  dilata- 
tion are  always  caused  by  chloroform,  and  in  rare  instances  are  produced 
by  ether.  Both  chloroform  and  ether  are  capable  of  causing  arrest  of  the 
heart  by  a  direct  action  upon  the  viscus,  but  chloroform  is  more  apt  to 
cause  fatal  accidents  than  is  ether,  partly  because  its  influence  upon  the 
heart  is  very  much  more  decided,  and  partly  because  it  persists  much 
more  tenaciously  than  does  ether  in  its  action  upon  the  whole  organization 
after  its  administration  has  been  interrupted.  It  lets  go  its  hold  much 
less  easily  and  much  less  rapidly  than  does  ether.f 

Alexander  Wilson  believes  that  the  ' '  cardiac  failure1 '  of  chloro- 
formization  is  chiefly  a  vaso-motor  paralysis.  Undoubtedly  vaso-motor 
paralysis  plays  a  part  in  the  production  of  the  untoward  results,  but  we 
see  no  sufficient  reason  for  supposing  that  it  is  the  chief  factor. 

Another  fact  worthy  of  notice  is  the  question  whether  the  lowered 
blood-pressure  itself  has  any  effect  upon  the  respiration.  In  a  research 

*  Further,  see  cases  reported  by  Alexander  Wilson  (London  Lancet ',  September  n, 
1897) ;  also  by  Jamieson  (Australia  Med.  Gaz.,  1903,  xxii.). 

t  A  possible  explanation  of  this  peculiar  tenacity  is  that  chloroform  is  stored  in  the 
nerve-centres,  outside  of  the  blood-vessels.  Julius  Pohl  (Arch  f.  Exp.  Pathol.  u. 
Pharm.,  1891,  xxviii.)  affirms  that  his  analyses  have  proved  that  more  chloroform  exists 
during  the  narcosis  in  the  brain-tissues  than  in  the  blood  coming  to  it. 


106  GENERAL  REMEDIES. 

published  by  H.  C.  Wood  and  W.  S.  Carter,8  it  was  proved  that  lowered 
arterial  pressure  has  only  a  comparatively  feeble  effect  upon  the  respira- 
tion, although  a  great  fall  of  pressure  does  depress  the  respiratory  func- 
tion. Evidently  prolonged  failure  of  respiration  tends  to  depress  the 
circulation,  and  prolonged  failure  of  circulation  tends  to  depress  the  respi- 
ration. The  two  functions  are  thus  far  interrelated.* 

On  account  of  its  being  less  dangerous,  ether  should  always  be  selected 
as  the  anaesthetic  agent  in  general  surgery  unless  definite  reasons  exist  for 
the  preference  of  chloroform.  These  reasons  may  be  epitomized  as  fol- 
lows. First,  when,  as  in  the  case  of  war,  circumstances  make  it  practically 
impossible  to  obtain  the  bulkier  anaesthetic.  Second,  when  the  symptoms 
themselves  are  of  such  character  as  immediately  to  threaten  life,  especially 
if  at  the  same  time  there  be,  as  in  a  tetanic  convulsion,  some  existing  con- 
dition which  greatly  interferes  with  the  entrance  of  the  anaesthetic  into  the 
lungs.  Third,  the  existence  of  certain  contra-indicating  bodily  conditions 
hardly  to  be  spoken  of  as  disease.  How  cogent  the  reasons  under  the 
present  heading  are  to  be  considered  we  are  uncertain,  but  F.  W.  Hewitt 
affirms  that  in  old  people  with  very  rigid  chests  etherization  is  often 
attended  by  great  difficulty  and  chloroform  is  well  borne,  and  also  cites 
extreme  obesity  as  a  bodily  state  in  which  ether  is  not  well  borne,  and  in 
which  chloroform  or  a  mixture  of  ether  and  chloroform  is  preferable. 
Fourth,  existence  of  certain  diseases  which,  to  a  greater  or  less  extent, 
not  only  contra-indicate  the  use  of  an  anaesthetic,  but  also,  when  the  anaes- 
thetic must  be  used,  modify  the  choice  of  the  agent  by  the  surgeon. 
The  existence  of  a  contra-indicating  disease  does  not  forbid  the  use  of  an 
anaesthetic.  If  a  major  surgical  operation  be  imperatively  demanded, 
and  if  it  be  impossible  by  the  use  of  local  anaesthetics  to  prevent  the  pain 
and  emotional  excitement  which  would  attend  the  operation  in  a  perfectly 
conscious  sensitive  patient,  the  surgeon  must  decide  whether  the  needs  of 
the  case  overbalance  the  added  risk  to  the  operative  procedure.  The 

*  Mixed  Anesthetics.—^  number  of  combinations  of  one  or  more  anaesthetics  have 
been  to  a  greater  or  less  extent  used  by  surgeons  with  the  hope  of  overcoming  or  avoid- 
ing the  deleterious  effects  of  the  one  ingredient  by  the  action  of  another.  The  most  used 
of  these  is  the  so-called  A.  C.  E.  mixture,  composed  of  one  part  of  alcohol,  by  weight, 
two  parts  of  chloroform,  and  three  parts  of  ether.  The  latest  is  Schleich's  mixture,  in 
which  the  attempt  is  made  to  have  an  anaesthetic  the  boiling  point  of  which  shall  ap- 
proximate to  the  bodily  temperature,  and  for  this  purpose  benzine  is  used  as  a  diluent. 
The  proportions  of  Schleich's  mixture  are  three  parts  chloroform,  ten  parts  ether,  one 
part  benzine.  The  difficulty  with  all  these  combinations  is  that  their  ingredients  are  not 
chemically  combined  but  simply  mixed  together,  and  therefore  obey  each  the  law  of  its 
own  volatility;  so  that  the  surgeon  can 'never  be  certain  of  knowing  exactly  what  the 
patient  is  inhaling  at  any  time  ;  the  only  certainty  being  that  the  original  mixture  is  not 
being  taken  into  the  lungs.  In  regard  to  Schleich's  mixture,  H.  C.  Wood,  Jr.  (Phila. 
Med.  Journ.,  April,  1899),  has  demonstrated  that  the  benzine  is  not,  as  affirmed  by 
Schleich,  a  "  nearly  inert"  diluent ;  on  the  contrary,  it  is,  although  almost  devoid  of  anaes- 
thetic properties,  a  powerful  depressant  of  the  respiratory  centres  and  also  of  the  heart 
and  probably  of  the  vaso-motor  system.  It  is  evident  that  Schleich's  mixture  is  distinctly 
inferior  either  to  ether  or  chloroform  used  alone.  If  the  surgeon  is  intent  on  having  what 
may  be  termed  a  "  mixed  anaesthesia,"  it  would  seem  better  to  put  ether  upon  the  inhaler 
or  sponge,  and  then  a  few  drops  of  chloroform. 


ANESTHETICS.  107 

contra-indicating  diseases  are  of  such  importance  as  to  demand  here 
extended  consideration.  They  are  :  Organic  Brain  Diseases,  including 
Tumors ;  Atheromatous  Conditions  of  the  Blood-Vessels ;  Organic 
Affections  of  the  Heart,  of  the  Lungs,  and  of  the  Kidneys. 

Brain. — Brain-tumors  and  other  organic  forms  of  cerebral  disease  are 
very  serious  centra-indications  to  the  use  of  anaesthetics  ;  even  where  there 
is  no  demonstrable  brain-lesion,  if  there  be  reason  strongly  to  suspect 
atheroma  of  the  vessels,  anaesthesia  should  be  induced  with  the  greatest 
reluctance.  In  a  number  of  cases  apoplexy  has  resulted  during  or  imme- 
diately after  the  anaesthesia.  Moreover,  death  has  frequently  abruptly 
occurred  immediately  after  the  sudden  removal  of  a  large  cerebral  tumor — 
the  introduction  of  the  finger  between  the  lobes  of  the  brain — or  other 
procedure  which  affects  the  intracranial  pressure.  These  deaths  have 
resulted  both  from  respiratory  failure  and  from  sudden  cardiac  arrest,  and 
are  probably  the  result  of  the  loss  of  the  resisting  power  of  the  respiratory 
and  vaso-motor  centres,  making  them  unable  to  withstand  variations  of 
brain-pressure  which  in  their  normal  condition  would  not  seriously  influ- 
ence them.  It  is  evident  that  the  surgeon  should  be  as  careful  as  possible 
in  his  operative  procedures  to  avoid  sudden  disturbances  of  the  brain. 

In  regard  to  the  choice  of  the  anaesthetic  in  a  cerebral  case  there  would 
seem  to  be  more  danger  of  apoplectic  hemorrhage  from  the  use  of  ether 
than  from  chloroform,  on  account  of  the  increase  of  arterial  pressure  pro- 
duced by  ether,  but  the  persistency  of  chloroform  and  the  depressing 
influence  which  it  has  upon  the  heart  are  much  more  serious  disadvantages 
than  any  possible  increase  of  blood-pressure  by  ether  ;  and  in  a  discussion 
which  took  place  in  the  College  of  Physicians  of  Philadelphia,  November, 
1902,  a  number  of  cerebral  surgeons  of  large  experience  were  unanimous 
in  asserting  that  in  cerebral  surgery  ether  is  the  least  dangerous  anaesthetic. 

Disease  of  the  Heart. — When  valvular  disease  of  the  heart  does  not 
produce  any  distinct  functional  disarrangement  of  the  heart,  and  when 
the  heart-muscle  is  in  a  fair  condition  of  health,  anaesthesia  may  be 
induced,  provided  the  circumstances  of  the  case  are  such  as  to  justify  the 
surgeon  taking  a  slightly  increased  risk.  The  key  to  the  situation  is  not  the 
valvular  lesion,  but  the  condition  of  the  muscle.  A  loud  murmur  usually 
depends  for  its  loudness  not  only  upon  the  character  of  the  valvular  lesion 
but  also  upon  the  force  which  drives  the  blood  through  the  diseased  orifice. 
A  loud  murmur  is,  therefore,  on  the  whole,  not  more  strongly  contra- 
indicative  of  anaesthesia  than  is  a  feeble  one  ;  indeed,  as  the  feeble  murmur 
is  more  commonly  associated  with  feeble  heart-walls,  greater  care  must  be 
exercised  when  such  murmur  exists  than  when  a  loud  bruit  everywhere 
forces  itself  upon  the  physician's  attention.  In  all  cases  of  heart  disease, 
whenever  it  is  possible  to  avoid  the  use  of  an  anaesthetic  by  the  employ- 
ment of  cocaine  or  by  other  local  device,  this  should  be  done.  No  condi- 
tion of  the  heart  is,  however,  an  absolute  centra-indication  to  the  use  of 
the  anaesthetic  ;  under  certain  circumstances  anaesthesia  may  be  produced 
when  the  heart  is  in  advanced  fatty  degeneration.  It  must  be  remem- 


io8  GENERAL  REMEDIES. 

bered  that  the  shock  and  nerve-strain  which  attend  a  major  surgical  oper- 
ation without  anaesthesia  would  endanger  the  arrest  of  a  fatty  heart  even 
to  a  greater  degree  than  would  the  anaesthesia,  so  that  the  question  is, 
after  all,  as  to  the  imperativeness  of  the  proposed  operation. 

In  diseases  of  the  heart  the  action  of  chloroform  upon  the  heart  makes 
it  very  dangerous.  In  cases  with  wide-spread  pulmonic  engorgement, 
and  a  tendency  to  exudation  into  the  lung-vessels  and  smaller  bronchial 
tubes.  The  local  irritant  action  of  ether  upon  the  mucous  membranes  is 
so  deleterious  that  the  surgeon  is  placed,  as  it  were,  between  Scylla  and 
Charybdis,  and  may  in  an  individual  case  have  great  difficulty  in  deciding 
what  is  best.  Some  surgeons  prefer  under  these  circumstances  the  so-called 
A.  C.  E.  Mixture,  which  is,  however,  of  very  doubtful  advantage  (see 
page  1 06 — note).  A  better  mixture  consists  of  six  parts  of  ether  and  one 
of  chloroform,  added  together  at  the  time  of  use.  Chloroform  is  especially 
dangerous  when  orthopnoea  exists  ;  it  is  doubtful  whether  in  such  a  case 
its  use  is  ever  justifiable. 

Disease  of  the  Respiratory  Apparatus. — The  existence  of  severe  or- 
ganic disease  of  the  lungs  seems  to  be  a  less  serious  bar  to  the  use  of 
anaesthetics  than  would  be  naturally  expected.  Of  all  the  chronic  pul- 
monic affections,  probably  emphysema,  associated  as  it  so  frequently  is 
with  weakness  of  the  right  heart,  causes  the  most  solicitude  to  the  anaes- 
thetizer.  The  irritant  local  action  of  ether  is  an  important  element  when 
the  lining  membrane  of  the  tubes  or  air-vessels  is  seriously  implicated  ; 
indeed,  our  own  opinion  is  very  positive  that  in  some  of  the  deaths  which 
have  occurred  in  persons  with  diseased  kidneys  from  oedema  of  the  lungs 
directly  after  etherization  the  cause  of  death  has  been  the  local  irritant 
action  of  the  ether.*  It  would  appear  also  that  wide-spread  organic 
changes  in  the  lungs  sometimes  so  interfere  with  the  absorption  of  ether 
that  it  becomes  exceedingly  difficult  to  produce  complete  anaesthesia.  The 
dictum  of  Hewitt,  that  in  extreme  emphysema,  in  chronic  bronchitis 
attended  by  expectoration  and  dyspncea,  and  in  advanced  pulmonary 
phthisis,  chloroform  or  some  other  mixture  containing  chloroform  should 
be  employed,  is,  we  believe,  correct. 

*  Ether  Pneumonia. — Severe  and  even  fatal  pneumonia  has  so  frequently  followed  the 
use  of  anaesthetics  that  the  possibility  of  its  occurrence  must  be  considered  one  of  the 
serious  dangers  of  anaesthesia.  Allowing  that  particles  of  food  may  enter  the  lungs 
during  the  narcosis  and  produce  inflammatory  changes,  there  has  been  a  tendency  to 
believe  that  ether  pneumonia  more  frequently  follows  the  use  of  ether  than  of  chloro- 
form, and  is  due  to  the  local  irritant  action  of  the  ether.  The  research  of  Richard 
Holscher9  has  led  him  to  the  conclusion  that  the  pneumonia  is  really  due  to  the  in- 
halation of  bacteria  from  the  mouth  into  the  lung,  that  during  etherization  there  is  prac- 
tically no  irritation  of  the  bronchial  mucous  membranes  by  ether,  and  that  the  rales 
which  are  heard  during  the  narcosis  are  due  to  the  inhalation  of  saliva,  which  may  largely 
be  avoided  by  lowering  the  head,  turning  it  to  one  side,  and  keeping  the  mouth  as  free 
as  possible  from  the  secretion.  Any  mechanical  obstacle  to  breathing,  according  to  Hol- 
scher, greatly  increases  the  likelihood  of  the  inspiration  of  saliva,  and  the  consequent 
danger  of  pneumonia.  According  to  our  belief,  this  research,  although  extremely  im- 
portant and  suggestive  as  pointing  out  one  cause  of  ether  pneumonia,  does  not  disprove 
the  deleterious  effect  of  the  irritant  action  of  ether. 


ANESTHETICS.  109 

In  all  cases  of  lung  disease  it  is  important  to  remember  that  the  more 
chronic  the  disorder  the  less  important  is  it  as  a  contra-indication  to  the 
use  of  an  anaesthetic,  and  that  anaesthetics  are  especially  badly  borne  when 
there  is  acute  or  subacute  pulmonary  disease.  Only  under  the  most 
urgent  circumstances  should  anaesthesia  be  attempted  when  in  an  acute 
pulmonary  disease  the  symptoms  are  of  sufficient  intensity  to  produce 
even  slight  dyspnoea.  In  recent  pleurisy  or  pleuro-pneumonia,  with  any 
embarrassment  of  the  respiration  or  duskiness  of  the  countenance,  anaes- 
thetization  is  attended  by  very  grave  risk. 

In  obstructive  laryngeal  disease,  or  when  contraction  of  the  lumen  of 
the  trachea,  either  from  within  or  without,  produces  dyspnoea,  extreme 
caution  must  be  exercised  in  the  use  of  the  anaesthetic.  Under  these  cir- 
cumstances the  chances  of  ether  increasing  the  mechanical  asphyxia  by 
irritating  the  larynx  or  trachea  are  very  great,  so  that  chloroform  is  pref- 
erable ;  or  chloroform  may  be  employed  at  first,  and  ether  given  when 
the  reflexes  have  been  abolished  by  the  obtunding  of  the  nerve-centres. 
When  the  laryngeal  obstruction  is  of  the  nature  of  a  spasm. and  not  of  an 
organic  change,  the  use  of  the  anaesthetic  is  free  from  extraordinary  dan- 
ger ;  but  it  must  be  remembered  that  frequently  in  such  cases  there  is 
more  or  less  laryngeal  irritation,  so  that  chloroform  is  preferable  to  ether, 
— a  conclusion  which  is  strengthened  by  the  necessity  which  often  exists 
for  the  prompt  action  of  the  anaesthetic. 

In  certain  cases  the  mechanical  obstruction  may  be  a  tumor  in  the 
mouth  or  other  lesion  above  the  respiratory  tract  proper,  but  if  the  respi- 
ration be  interfered  with,  the  general  principles  just  enunciated  hold  good. 

Hepatic  Conditions. — L.  G.  Guthrie35  has  called  attention  to  the  exces- 
sive fatality  attending  the  use  of  chloroform  in  children  suffering  from  fatty 
degeneration  of  the  liver.  The  time  of  death  in  nine  recorded  cases  was 
from  ten  hours  to  nine  days  after  the  operation,  so  that  the  cases  really 
belong  among  those  considered  in  the  After-effects  of  Anaesthesia  (see 
page  116).  There  is  sufficient  ground  for  the  generalization  that  anaes- 
thesia should  be  produced  with  the  greatest  reluctance  in  all  persons  suf- 
fering from  chronic  fatty  degeneration  of  the  liver,  and  that  when  anaes- 
thesia must  be  produced  in  such  cases,  ether  and  not  chloroform  should 
always  be  selected. 

Diseases  of  the  Kidney. — So  far  as  our  reading  goes,  Thomas  A. 
Emmet  was  the  first  to  report  cases  of  fatal  urinary  suppression  produced 
by  the  inhalation  of  ether  in  persons  suffering  from  chronic  Bright' s  dis- 
ease. His  statements  have  been  followed  by  reports  of  numerous  similar 
cases,  and  led  to  the  wide-spread  opinion  that  ether  should  not  be  used 
when  there  was  chronic  disease  of  the  kidneys.  It  is  now,  however, 
established  that  chloroform  is  capable  of  causing  severe  renal  irritation, 
and  the  whole  drift  of  the  evidence  is  to  show  that  in  this  respect  it  is 
much  more  active  than  is  ether,  so  that,  although  renal  disease  is  a  contra- 
indication to  the  use  of  any  anaesthetic,  if  anaesthesia  must  be  produced 
under  the  circumstances,  ether  is  safer  than  is  chloroform. 


no  GENERAL  REMEDIES. 

Albuminuria  may  be  considered  a  sufficiently  accurate  evidence  of  renal  irri- 
tation to  enable  the  practitioner  to  use  it  as  a  working  test.  A  large  number  of 
studies  as  to  the  effect  of  anaesthetics  upon  the  urine  have  been  made  by  different 
clinicians.  Eisendrath 81  states  that  albuminuria  was  produced  in  his  cases, — 25  per 
cent,  by  ether,  32  per  cent,  by  chloroform  ;  and  casts  were  found  in  28.3  per  cent, 
after  ether,  21.4  per  cent,  after  chloroform.  In  Wunderlich's  studies  the  results  were 
24.6  per  cent,  after  ether,  34.8  per  cent,  after  chloroform.*  Ogden  found  tube-casts 
in  70  per  cent,  of  etherizations.  Statements  of  other  investigators,  whom  we  shall 
not  quote  in  detail,  indicate  that  the  occurrence  of  distinct  albuminuria  after  anaes- 
thesia in  persons  with  sound  kidneys  is  less  frequent  than  these  statistics  would 
indicate  ;  but  all  the  statistics  strongly  point  towards  the  opinion  that,  whilst  both 
ether  and  chloroform  seriously  affect  the  kidneys,  ether  is  less  dangerous  than  is 
chloroform.  These  clinical  conclusions  are  certainly  borne  out  by  the  results 
obtained  in  animals  by  various  investigators.  According  to  Kemp  and  Thompson, 
during  etherization  in  the  animal  there  is  always  accompanying  the  first  rise  of  blood- 
pressure  an  expansion  of  the  kidney  followed  by  a  shrinkage  of  the  organ,  if  the 
anaesthesia  be  prolonged  ;  but  this  has  been  found  by  Buxton  and  Levy  ( B.  M.  J. , 
1900,  ii.,  September  22)  not  to  be  a  constant  phenomenon.  Buxton  and  Levy  failed 
to  produce  complete  suppression  with  ether,  but  did  get  lessening  of  the  secretion, 
and  as  the  result  of  their  research  think  that  there  is  very  little  evidence  to  show 
that  ether  has  an  active  direct  influence  upon  the  secreting  structure  of  the  kidney. 
All  observers  seem  to  find  that  in  chloroformization  the  volume  and  activity  of  the 
kidney  steadily  decrease. 

The  choice  of  the  surgeon  between  the  two  great  anaesthetics  should, 
in  most  cases  of  renal  disease,  be  influenced  by  the  existence  of  secondary 
effects  of  the  disease.  If,  for  instance,  in  any  case  there  were  pronounced 
degeneration  of  the  heart-muscles,  the  selection  should  fall  upon  ether. 
If  there  were  any  reason,  on  the  other  hand,  to  believe  that  there  was  in 
the  case  a  tendency  to  serous  exudation,  the  danger  of  the  production  of 
cedema  of  the  lungs  by  ether  through  its  local  irritant  action  would  be 
sufficient  reason  for  the  selection  of  chloroform.  In  doubtful  cases  of  car- 
diac complication  it  might  be  good  practice  to  commence  the  anaesthesia 
with  ether,  and,  when  once  its  stimulating  action  was  established,  to  con- 
tinue the  narcosis  by  the  use  of  chloroform. 

After-effects  of  Anesthesia. — Many  yeirs  ago  Liman  affirmed  that  at 
least  some  of  the  deaths  following  operations  which  have  been  attributed 
to  the  operative  procedure  have  been  due  to  the  chloroform.  The  cor- 
rectness of  this  view  we  have  demonstrated  by  having  such  deaths  occur 
in  the  lower  animals  after  both  chloroform  and  ether  when  there  had  been 
no  surgical  operation,  the  animal  regaining  consciousness,  but  by  and  by 
passing  into  a  condition  of  profound  asthenia,  with  loss  of  all  functional 

*  For  elaborate  articles  on  the  action  of  chloroform  on  the  urine  and  kidneys,  see  F. 
Nachod  (Archiv  f.  Klin.  Chirurgie,  1890,  li.),  also  Offergeld36.  Babacci  and  Bebi  (II 
Polyclinico,  1896,  iii.),  reach  the  conclusion  that,  although  ether  produces  slight  changes 
in  the  kidneys  more  frequently  than  does  chloroform,  it  never  causes  such  profound 
alteration. 

As  bearing  upon  the  question  of  the  effect  of  ether  anaesthesia  upon  the  kidney, 
it  is  interesting  to  state  that  F.  S.  Watson  and  W.  T.  Bailey  have  found  that  in  the  normal 
kidney,  so  far  as  the  so-called  Phloridzin  Test  is  concerned,  ether  increases  functional 
activity  of  the  kidney,  but  when  the  kidney  is  already  diseased  seems  from  the  beginning 
to  depress  the  renal  function  (Med.  and  Surg.  Rep.,  Boston  City  Hospital,  1902). 


ANESTHETICS.  m 

power,  ending  in  death.     These  deaths  are  due  to  anatomical  changes  in 
important  organs. 

About  a  decade  since  it  was  shown  by  Unger  and  by  Path,21  that  when,  in  the 
dog,  narcosis  is  maintained  for  a  length  of  time  by  the  inhalation  of  chloroform, 
there  is  produced  a  fatty  degeneration  which  is  usually  most  marked  in  the  liver  and 
kidneys  and  in  the  heart-muscles,  but  may  be  pronounced  in  the  spleen,  in  the  gen- 
eral epithelial  tissues,  and  in  the  voluntary  muscles.  These  researches  have  been 
confirmed  in  their  general  results  in  numerous  experiments  upon  animals  by 
Strassmann,22  by  Ostertag,23  and  by  Kast  and  Mester.24  Tedeschi,25  in  an  elaborate 
study  upon  guinea-pigs,  has  found  that  the  first  anatomical  alteration  produced  by 
chloroform  consists  of  cloudy  swelling  which  may  go  on  to  degeneration,  or  may 
subside  ;  and  that  even  when  a  considerable  degree  of  apparent  fatty  degeneration 
has  occurred  recovery  is  possible.  He  also  found  that  these  alterations  were  most 
severe  in  the  nervous  system,  which  is  somewhat  contrary  to  the  general  opinion. 
Botscharoff 26  and  S.  Schmidt37  assert  that  they  have  demonstrated  alteration  of  the 
heart-ganglia,  especially  vacuolation  of  the  cells,  after  prolonged  chloroformization. 

Eugene  Fraenkel '"  found  in  four  human  subjects,  dying  after  pro- 
longed chloroformization,  wide-spread  necrotic  degeneration,  especially 
affecting  the  heart-muscles  and  the  epithelium  of  the  kidney,  and  Car- 
michael  and  Beattie37  and  Stiles  and  Macdonald M  have  reported  wide- 
spread fatty  changes  in  man  following  chloroform  anaesthesia.  As  these 
observations  have  been  abundantly  confirmed  ( Handler,  ^  Ambrosius,29  and 
our  own  laboratory),  it  must  be  considered  proved  that  chloroform  has 
the  power  of  producing  tissue-degeneration,  ending  in  death. 

The  possibility  of  after-effects  from  the  anaesthetic  should  certainly 
influence  the  choice  of  surgeons. 

According  to  Desgrez  and  Nicloux,32  chloroformization  of  the  lower 
animals  causes  a  great  increase  in  the  amount  of  carbon  monoxide  in  the 
blood.  As  this  substance  is  produced  by  the  decomposition  of  chloro- 
form by  an  alkali,  and  as  Desgrez  and  Nicloux  have  failed  to  find  that  it 
is  increased  in  the  blood  by  etherization,  it  probably  is  produced  in  the 
blood  by  the  destruction  of  the  chloroform,  which  destruction  must  be 
accompanied  by  the  formation  of  various  chlorine  compounds. 

On  the  other  hand,  the  destruction  of  ether  in  the  system  can  scarcely 
yield  other  than  harmless  educts,  so  that,  a  priori,  after-effects  are  much 
more  probable  from  the  use  of  chloroform  than  from  ether.  This  proba- 
bility is  strongly  confirmed  both  by  experimental  and  clinical  evidence. 
As  the  result  of  many  years'  experience  in  the  physiological  laboratory, 
we  are  very  sure  that  after-deaths  are  much  more  frequent  in  animals 
which  have  been  chloroformed  than  after  ether. 

In  experiments  performed  by  William  Carter  and  H.  C.  Wood  in  the 
University  laboratory,  tissue-changes  similar  to  those  caused  by  chloro- 
form were  found  in  the  dog  after  etherization.  These  studies  have  been 
corroborated  by  the  researches  of  Ferdinand  Schenck  *°  and  of  Tedeschi. 
Again,  in  a  woman  whose  death  occurred  twenty-four  hours  after  a  pro- 
longed etherization  in  the  University  Hospital,  without  obvious  cause, 


H2  GENERAL  REMEDIES. 

wide-spread  tissue-changes  were  found.  Miiller59  found  that  chloroform, 
ether,  ethyl  chloride,  ethyl  bromide,  and  chloral  hydrate  were  all  capable 
of  producing  these  changes,  but  that  they  were  less  marked  after  ether 
than  after  chloroform.  In  his  experiments  it  was  found  that  if  a  second 
narcosis  was  produced  before  the  repair  processes  were  completed  the 
baneful  effects  were  much  intensified  even  if  different  anaesthetics  were 
used.  He  warns  therefore  that  after  a  prolonged  anaesthesia  no  second 
narcosis  should  be  undertaken  for  at  least  three  days  later. 

In  this  connection  may  be  mentioned  the  observations  of  E.  Becker10* 
who,  in  two  hundred  and  fifty  experiments  made  with  ether,  ethyl  bro- 
mide, and  chloroform,  found  that  the  anaesthesia  was  followed  by  pro- 
nounced acetonuria,  which  he  believed  to  be  due  to  increased  destruction 
of  albumin.  In  three  diabetics  he  noticed  great  increase  in  the  amount 
of  acetone  in  the  urine, — an  indication  that  under  certain  circumstances 
diabetes  should  be  considered  a  centra-indication  to  the  use  of  an  anaes- 
thetic. Brachett  Stone  and  Low  *°  report  seven  cases  of  fatal  acetonuria 
following  ether  anaesthesia  in  children  suffering  with  muscular  atrophies. 

ADMINISTRATION. — The  methods  of  the  administration  of  chloroform 
and  ether  naturally  differ.  With  ether  the  nearer  the  saturation  of  the 
air  is  reached  the  quicker  will  be  the  induction  of  anaesthesia,  and  the 
effort  has  generally  been  to  give  the  anaesthetic  in  as  concentrated  a  form 
as  possible.  It  is  certain,  however,  that  the  disagreeable  symptoms  of  the 
first  stage  of  ether  may  be  largely  avoided  by  the  primary  use  of  a  very 
much  diluted  vapor.  According  to  Snow,  air  at  80°  F. ,  when  saturated 
with  ether,  contains  seventy-one  per  cent,  of  the  vapor. 

Ether  was  formerly  habitually  given  by  making  out  of  stiff  paper  or 
card-board  a  cone  that  would  fit,  when  a  saturated  napkin  had  been 
placed  into  it,  over  the  nose  and  mouth  of  the  patient.  Although  by  this 
method  anaesthesia  is  rapidly  insured,  the  discomfort  of  the  patient  is 
brought  to  a  maximum.  Much  better  results  are  reached  by  laying  five 
or  six  thicknesses  of  surgical  gauze  lightly  over  the  mouth  and  nose  01  the 
patient,  and  then  dropping  from  a  properly  prepared  bottle  the  ether, 
drop  by  drop,  upon  the  gauze  just  below  the  nostrils. 

Ether  is  also  given  by  means  of  various  inhalers ;  the  so-called 
' '  closed' '  inhalers,  in  which  there  is  only  a  small  supply  afforded  of  atmos- 
pheric air,  are,  in  our  opinion,  exceedingly  dangerous  ;  whilst  the  Allis 
inhaler  offers  the  perfection  of  method  for  the  production  of  ether  anaes- 
thesia, f  In  Europe  various  inhalers  are  employed  for  the  administration 

*  Confirmed  by  Luzzati  (Comment.  Clin.,  1895). 

t  The  inhaler  invented  by  O.  H.  Allis  is  based  upon  the  theory  that  the  patient  to  be 
etherized  should  be  supplied  with  an  abundance  of  air  impregnated  with  the  vapor  of 
ether.  It  consists  essentially  of  a  series  of  foldings  of  muslin  on  a  wire  framework, 
arranged  almost  like  the  gills  of  a  fish,  so  as  to  allow  the  air  to  pass  freely  through,  but 
everywhere  to  come  in  contact  with  the  ether.  It  should  be  placed  upon  the  face  of  the 
patient  dry,  and  the  ether  gradually  poured  on  from  a  so-called  "  Polyclinic"  bottle,  which 
has  two  fine  tubes  through  the  cork,  one  short,  to  admit  air,  and  one  reaching  to  near  the 
bottom,  so  that  the  ether  can  be  poured  through  it  in  a  fine  stream. 


ANESTHETICS.  113 

of  chloroform,  but  in  this  country  they  are  rarely,  if  ever,  used.  A 
napkin  or  a  few  folds  of  surgical  gauze  may  be  laid  over  the  nostrils  and 
mouth,  and  the  chloroform  dropped  upon  this.  Whatever  plan  be  em- 
ployed, it  is  of  vital  moment  that  the  vapor  be  well  diluted  ;  not  more  than 
three  and  one- half  per  cent,  of  it  should  be  contained  in  the  inspired  air. 

The  use  of  ether  at  night  requires  care.  We  have  seen  a  flame,  by 
lighting  the  vapor,  pass  over  eight  feet  and  set  on  fire  the  ether  sponge  and 
the  patient.  Since  the  vapor  of  ether  is  heavier  than  air,  when  the  anaes- 
thetic is  used  at  night  the  light  should  always  be  elevated.  The  adminis- 
tration of  chloroform  at  night  is  also  not  free  from  danger.  Attention  has 
been  called  by  various  practitioners  to  violent  catarrhal  inflammations 
of  the  respiratory  passages,  and  even  to  fatal  pneumonias,  which  have 
been  produced  by  the  use  of  chloroform  in  confined  rooms  with  artificial 
light.  It  has  been  shown  by  the  analyses  of  Bosshard  and  others  that, 
under  the  circumstances  mentioned,  by  the  decomposition  of  chloroform 
there  is  liberated  free  chlorine  and  also  phosgene  gas,  to  which  probably 
are  due  the  local  inflammations.* 

ACCIDENTS. — In  1848  Dume"ril  and  Demarquay11  showed  that  during 
anaesthesia  there  is  a  reduction  of  temperature.  This  has  been  confirmed 
by  Bouisson 12  and  by  Sulzynski. 1S  This  fall  of  temperature  may,  when 
narcosis  is  prolonged,  amount  to  2°  F.  Whether  this  fall  of  temperature 
be,  as  asserted  by  Scheinson,14  due  to  a  lessened  production  of  the  bodily 
heat,  or  whether,  as  seems  to  us  more  probable,  it  be  the  outcome  of 
an  increased  dissipation  of  bodily  heat,  is  of  no  practical  importance  to 
the  surgeon.  The  immediate  lesson  is,  that  prolonged  severe  operation 
should  be  done  in  very  hot  rooms,  and  that  when  the  bodily  heat  falls  it 
should  be  maintained  by  the  external  use  of  heat,  in  some  cases  even  by 
the  employment  of  a  hot-water  mattress. 

In  practical  anaesthesia  it  is  a  matter  of  the  gravest  importance  to 
recognize  the  coming  on  of  accidents.  Cessation  of  respiration  may  be 
sudden  ;  more  usually  it  is  gradual.  Irregularities  of  respiration,  and 
increasing  shallowness  of  respiration  appearing  during  the  advanced  stages 
of  anaesthesia,  are  most  urgent  signals  for  the  withdrawal  of  the  anaes- 
thetic and  the  use  of  prompt  measures  for  relief.  Failure  of  the  pulse  is, 
of  course,  of  still  more  serious  import,  but  it  is  often  so  sudden  as  not  to 
be  noticed  immediately.  It  is  always  accompanied  or  immediately  pre- 
ceded by  a  peculiar  change  in  the  facial  color  or  expression,  and  the 
anaesthetizer  should  therefore  not  merely  watch  the  pulse,  but  especially 
the  face.f 

In  discussing  the  treatment  of  the  accidents  of  anaesthesia  it  seems 
essential  first  to  point  out  certain  procedures  which  have  been  very  largely 

*  Consult  Zweifel  (Berl.  Klin.  Wochensch.,  1889),  D.  R.  Patterson  (London  Prac- 
titioner, xlii.),  and  Brandenberg  (Corr.  Bl.  f.  Schweizer  Aerzte,  1897,  xxvii. ;  Arch.f. 
Hygiene,  1891,  xiii.). 

t  For  methods  of  determining  the  percentage  of  chloroform  in  a  mixture  of  its  vapor 
with  air,  see  Brit.  Med.  Journ.,  1903,  vol.  i.  p.  1420. 

8 


practised  in  the  past  and  are  still  not  rarely  employed,  but  which  are 
either  of  no  value  or  harmful.  The  first  of  these  is  as  to  the  use  of  ether ; 
second,  as  to  the  administration  of  alcohol. 

Hypodermic  injections  of  ether,  although  frequently  employed,  are  so  absolutely 
absurd  that  one  wonders  at  the  fatuity  of  surgeons.  Ether  in  the  blood  acts  as 
ether,  whether  it  finds  entrance  through  the  lungs,  through  the  rectum,  or  through 
the  cellular  tissue  ;  and  the  man  who  would  inject  ether  hypodermically  into  a 
patient  who  is  dying  from  ether,  should,  to  be  logical,  also  saturate  a  sponge  with 
the  ether  and  crowd  it  upon  his  unfortunate  victim. 

Owing  to  the  closeness  of  the  relations  of  alcohol  to  ether  and  chloroform,  H. 
C.  Wood  many  years  ago  taught  that  the  administration  of  alcohol  during  anaesthesia 
was  a  doubtful  procedure  ;  subsequently,  R.  Dubois15  determined  that  in  the  alco- 
holized animal  much  less  chloroform  is  required  to  kill  than  in  the  normal  animal. 
Then  H.  C.  Wood36  experimentally  proved  that  alcohol  injected  into  the  vein  of  a 
dog  whose  heart  is  depressed  by  chloroform,  if  in  sufficient  dose  to  exert  any  per- 
ceptible influence,  always  increases  the  cardiac  weakness,  or,  if  in  considerable 
dose,  immediately  paralyzes  the  viscus.  Without  doubt  patients  have  been  killed 
by  alcohol  given  to  relieve  cardiac  failure  during  anaesthesia.  Experiments  similar 
to  those  with  alcohol  just  spoken  of  were  made  by  H.  C.  Wood :  with  ammonia, 
which  was  found  usually  to  have  a  distinct,  although  very  fugacious,  influence  upon 
the  chloroformed  heart ;  with  digitalis,  which  was  found  to  have  a  very  powerful 
stimulant  influence  upon  the  heart  and  blood-pressure  ;  with  amyl  nitrite,  which 
failed  to  produce  any  pronounced  influence  for  good  ;  with  caffeine,  which  seemed 
to  have  little  or  no  power  ;  and  with  strychnine,  which  had  some  slight  influence  upon 
the  blood-pressure,  but  an  enormous  one  upon  the  respiration  of  the  chloroformed 
animal.  Thus,  a  respiration  which  had  practically  ceased  for  ten  seconds,  sud- 
denly, under  the  influence  of  an  injection  of  strychnine,  became  very  quick  and  full. 
Cocaine  was  not  tried,  but  studies  made  with  it  since  upon  chloralized  dogs  indicate 
that  it  has  distinct  value,  especially  when  given  with  the  strychnine.  At  the  time 
of  the  experiments  just  spoken  of  adrenalin  had  not  been  discovered,  but  as  the 
most  powerful  known  stimulant  to  the  circulation  it  must  be  of  great  possible  value 
in  the  treatment  of  the  cardiac  accidents  of  anaesthesia. 

Before  epitomizing  the  treatment  of  the  accidents  of  ansesthesia  it 
seems  proper  to  discuss  in  detail  certain  mechanical  measures  which  may 
be  practised  with  advantage, — namely,  Inversion  of  the  Body,  Cardiac 
Massage,  and  Artificial  Respiration. 

Inversion  of  the  Body. — In  the  first  edition  of  the  present  treatise  it  was  written  : 
"Whenever  there  is  any  failure  of  the  heart's  action,  as  is  nearly  always  the  case, 
the  body  should  be  laid  at  an  angle  of  forty  degrees,  with  the  head  downward,  so 
as  to  favor  the  passage  of  arterialized  blood  to  the  brain"  (E.  L.  Holmes 16).  Some 
years  after  this  the  method  was  asserted  in  France  to  have  just  then  originated  with 
Nelaton.  It  undoubtedly  has  value.  The  body  of  the  animal  whose  circulation 
has  been  paralyzed  by  chloroform  acts  in  a  measure  like  a  tube  filled  with  liquid. 
When  the  feet  are  raised  above  the  head  there  is  a  marked  increase  in  the  blood- 
pressure  in  the  carotid,  with  decrease  in  the  blood-pressure  in  the  femorals  ;  and 
when,  on  the  other  hand,  the  feet  are  dropped  below  the  head,  the  blood-pressure 
fails  in  the  carotid,  but  rises  in  the  femorals.  The  respiration  is  not  affected  by  the 
procedure,  but  a  heart  which  has  entirely  ceased  will  often  suddenly  resume  its 
work  when  the  feet  are  elevated.  Inversion  causes  the  blood  which  has  collected 
in  the  extremely  relaxed  abdominal  vessels  to  flow  into  and  distend  the  right  side 


ANAESTHETICS.  115 

of  the  heart,  and  this  distention  may  have  sufficient  influence  to  stimulate  into  action 
a  failing  organ. 

Cardiac  Massage. — In  1889  Prus33  succeeded  in  restoring  animals  to  life,  after 
cardiac  arrest  during  anaesthesia,  by  rhythmically  contracting  the  bared  heart  with 
his  fingers,  and  this  so-called  "cardiac  massage"  has  been  employed  to  a  consider- 
able extent  by  surgeons.  W.  W.  Keen  s*  collected  twenty-eight  recorded  cases  with 
four  successes  ;  since  this  paper  one  complete  recovery  has  been  reported  by  Sen- 
cert41.  Three  methods  have  been  used  :  (i)  By  compression  between  the  hands, 
one  being  applied  outside  the  chest  and  the  other  directly  upon  the  heart  after  an 
abdominal  section,  but  without  opening  the  diaphragm.  (2)  By  abdominal  section, 
and  after  opening  the  diaphragm  seizing  the  heart  within  the  pericardial  sac.  (3) 
By  resection  of  the  chest  wall,  incision  of  the  pericardium,  and  grasping  the  heart 
with  one  or  both  hands.  The  third  of  these  methods  involves  a  major  operation  in 
surgery,  adding  distinctly  to  the  surgical  dangers  of  the  patient.  Especially  when 
the  abdomen  has  already  been  opened  by  the  surgeon,  the  first,  and  even  the 
second  method  is  easily  practised  without  very  serious  surgical  results.  It  is  at 
present  doubtful  whether  cardiac  massage  will  ever  restore  cardiac  action  when  the 
intravenous  injection  of  adrenalin  and  the  practice  of  forced  artificial  respiration 
would  not  succeed,  but  to  the  use  of  these  methods  that  of  the  simpler  form  of 
cardiac  massage  (No.  i),  especially  in  abdominal  operations,  may  well  be  added. 

Artificial  Respiration. — The  one  measure  which  H.  C.  Wood  found  in  his  ex- 
periments upon  fatally  anaesthetized  animals  to  surpass,  in  practical  efficiency,  all 
others  combined  was  artificial  respiration,  by  means  of  which  animals  were  fre- 
quently resuscitated  after  all  cardiac  and  respiratory  movements  had  apparently 
ceased. 

It  is  evident  that  the  ordinary  methods  of  practising  artificial  respiration  in  man 
are  exceedingly  imperfect  and  feeble,  and  that  in  the  accidents  of  anaesthesia  so- 
called  forced  artificial  respiration  should  be  at  once  employed  (see  address  on 
Anesthesia).  The  principle  of  forced  artificial  respiration  consists  simply  of 
pumping  air  into  the  lungs  by  means  of  a  bellows.  Fell's  apparatus  is  efficient, 
but  unnecessarily  complicated  ;  a  simpler  one  is  described  in  the  foot-note.*  When 
no  apparatus  is  at  hand,  forced  insufflation  by  breathing  into  the  patient's  mouth 
may  be  tried.  A.  E.  Prince  n  reports  a  case  saved  in  this  way. 

In  using  this  apparatus,  the  mask  should  be  first  tried,  care  being  exercised  to  see 
that  the  tongue  is  well  drawn  forward  and  held  in  place  by  a  thread  through  it,  and 
that  the  epiglottis  is  kept  open.  If  the  lungs  do  not  fully  expand,  the  intubation- 
tube  may  be  used.  Whether  the  mask  or  the  intubation-tube  be  employed,  the 
lungs  should  be  thoroughly  but  slowly  expanded  by  each  stroke  of  the  bellows, 
and  a  respiratory  rate  of  about  sixteen  to  twenty  a  minute  be  steadily  maintained. 
It  is  essential  to  free  the  lungs  and  blood  of  chloroform  as  rapidly  as  possible,  by 
quickly  changing  the  residual  air  of  the  lungs  ;  but  of  course  due  care  must  be  ex- 
ercised that  no  force  sufficient  to  rupture  air-vesicles  be  employed.  When  the 

*  Apparatus  for  Artificial  Respiration. — Fell's  apparatus  consists  of  a  pair  of  foot 
bellows  by  which  air  is  forced  into  a  receiving  chamber,  which  is  connected  with  an 
apparatus  for  warming  the  air,  and  a  valve  which  can  be  opened  and  shut  by  a  movement 
of  the  finger.  This  valve,  in  turn,  leads  to  the  tracheal  tube.  When  the  valve  is  opened 
the  air  rushes  through  the  chamber  into  the  lungs  and  expands  them  ;  the  finger  is  lifted, 
the  valve  shuts,  the  lungs  contract,  and  so  the  respiration  goes  on. 

A  much  simpler,  cheaper,  and  probably  equally  efficient  apparatus  may  consist  simply 
of  a  pair  of  bellows  of  proper  size,  a  few  feet  of  india-rubber  tubing,  a  face-mask,  and 
two  sizes  of  intubation-tubes ;  there  should  also  be  set  in  the  tubing  a  double  tube,  with 
an  opening  similar  to  that  commonly  found  in  the  tracheal  canula  of  the  physiological 
laboratory,  so  that  the  operator  can  allow  the  escape  of  any  excess  of  air  thrown  by  the 
bellows.  Fell  (Journ.  Amer.  Assoc.,  1892,  xix.)  insists  on  the  superiority  of  his  appa- 
ratus, and  possibly  in  a  large  surgical  clinic  it  might  be  well  to  provide  his  rather  compli- 
cated mechanism. 


u6  GENERAL   REMEDIES. 

symptoms  are  protracted,  and  the  bodily  temperature  falls,  the  bodily  heat  must 
be  maintained  by  external  warmth,  and  the  temperature  of  the  room,  unless  the  air 
entering  the  lungs  be  artificially  heated,  should  not  be  less  than  80°  F. 

In  the  light  of  all  our  present  clinical  and  experimental  knowledge,  the 
following  rules  may  be  formulated  as  embodying  the  treatment  of  the 
accidents  of  anaesthesia  : 

First.  Unless  the  pulse  be  beating  actively,  partially  or  wholly  invert 
the  body  of  the  patient. 

Second.  Place  the  index  fingers  of  each  hand  upon  the  corresponding 
cornua  of  the  hyoid  bone,  whilst  the  middle  fingers  rest  upon  the  angle 
of  the  jaw,  and  then  press  forward  and  upward,  the  same  force  serving 
to  extend  the  head  upon  the  neck  ;  if  this  fail  to  open  the  glottis,  by 
means  of  a  tenaculum,  thrust  far  back  into  the  base  of  the  tongue,*  draw 
it  forward. 

Third.  Make  a  momentary  effort  to  stimulate  respiration  by  slapping 
the  chest,  by  douching  with  cold  water,  or  by  the  method,  suggested  by 
Hare,  of  pouring  a  little  ether  on  the  bared  abdomen,  so  as  to  get  the 
effect  of  cold.  Do  not  waste  time,  if  respiration  has  failed,  in  any  of  these 
attempts. 

Fourth.  Use  certain  drugs  as  follows  :  Ammonia  may  sometimes  be 
given  by  the  mouth,  but  ordinarily  is  of  no  value.  Strychnine  and 
cocaine,  administered  hypodermically  or  intravenously,  are  often  of  the 
greatest  service.  Digitalis  given  hypodermically  acts  too  slowly  to  be 
available  ;  probably  injected  intravenously  it  would  be  a  very  valuable 
remedy,  but  we  know  of  no  clinical  records  of  such  use.  Adrenalin, 
especially  in  cases  of  cardiac  failure,  administered  intravenously  in  hot 
(105°  F. )  normal  saline  solution,  f  may  be  of  the  utmost  service  ;  from 
twenty  to  thirty  minims  of  the  i  :  1000  adrenalin  solution  in  half  a  pint  of 
the  saline  solution  may  be  slowly  injected  in  cases  of  persistent  circulatory 
failure  ;  as  much  as  two  drachms  of  the  adrenalin  solution  in  two  pints  of 
the  normal  saline  may  be  given  in  the  course  of  one  and  a  half  hours. 
When  the  symptoms  are  not  very  alarming,  smaller  amounts  than  those 
spoken  of  above  are  preferable. 

Fifth.  Practise  artificial  respiration  immediately  and  very  actively 
throughout  (forced  respiration  if  the  apparatus  be  at  hand),  even  when 
the  heart  is  primarily  affected.  It  must  be  remembered  that  the  residual 
air  of  the  lung  may  retain  the  vapor  of  the  anaesthetic  and  continue  to 
yield  it  to  the  system  for  a  considerable  time  after  the  cessation  of  its 
administration. 

*  Benjamin  Howard  asserts  that  the  common  practice  of  drawing  out  the  tongue  has 
no  influence  in  raising  the  paralyzed  epiglottis,  which  he  affirms  can  be  accomplished 
only  by  extending  the  head  and  neck ;  but  in  the  elaborate  experiments  made  in  the 
University  laboratories  by  Hobart  A.  Hare  and  Edward  Martin  it  was  demonstrated 
that  the  method  of  Howard  is  inferior  to  that  given  in  the  text  (Medical  News,  1889). 

t  The  restorative  cardiac  action  of  hot  normal  salt  solution  intravenously  adminis- 
tered has  been  demonstrated  in  a  series  of  experiments  upon  animals  by  S.  Gomberg,20 
and  is  said  to  have  been  long  recognized  practically  in  Russia. 


ANAESTHETICS.  117 

LOCAL  ANESTHESIA. 

Of  the  drugs  which  are  employed  for  the  production  of  local  anaesthe- 
sia, cocaine  still  stands  pre-eminent,  but  its  common  use  for  other  purposes 
has  led  us  to  discuss  its  physiological  action  and  therapeutic  use  fully  in 
the  chapter  on  Delirifacients. 

EUCAINE. 

Under  the  name  of  eucaine  two  allied  chemical  substances  have  been  put  upon 
the  market,  each  depending,  according  to  Vinci,1  for  its  anaesthetic  properties  upon 
the  presence  of  a  benzoyl  molecule  in  its  constitution.  These  substances  have  been 
distinguished  in  commerce  by  the  names  of  Alpha-Eucaine  and  Beta-Eucaine. 
Alpha-Eucainr;  is  chemically  n-methyl-benzoyltetramethyl-y-oxypiperidincarboxy- 
licmethylester  ;  Beta-Eucaine  is  benzoylvinyldiacetonalkamine. 

At  one  time  alpha-eucaine  was  the  eucaine  of  the  market,  but  it  has  been  super- 
seded by  beta-eucaine  as  less  irritating  and  less  toxic.  Eucaine  of  the  drug  stores 
is  at  present  beta-eucaine.  Beta-eucaine  is  soluble  in  water  to  the  extent  of  about 
three  and  one-half  per  cent.  The  acetate  has  been  proposed  as  more  soluble. 

According  to  Vinci,2  alpha-eucaine  is  a  depressant  to  the  spinal  cord,  and  Ver 
Eecke  has  found  it  to  be  a  direct  muscle  paralyzant  which  acts  more  powerfully 
upon  the  heart-muscle  than  upon  the  voluntary  muscle,  so  that  death  from  cardiac 
diastolic  arrest  occurs  before  complete  general  paralysis.  Ver  Eecke  states  that  in 
mammals  the  arterial  pressure  is  markedly  affected  and  the  respiration  is  first 
stimulated  and  finally  paralyzed  centrically. 

The  statement  of  Ver  Eecke,3  that  the  drug  causes  increased  destruction  of 
nitrogenous  tissues,  is  scarcely  borne  out  by  the  tabulated  reports  of  his  experi- 
ments. Ver  Eecke  failed  to  find  the  poison  in  the  urine  after  its  administration, 
and  believes  that  it  undergoes  destruction  in  the  body.  According  to  Ver  Eecke, 
in  chronic  poisoning  with  alpha-eucaine  there  is  a  wide-spread  fatty  degeneration 
which  is  especially  marked  in  the  heart-muscle. 

Vinci  found  that  beta-eucaine  paralyzes  the  peripheral  motor  nerves  as  well  as 
the  sensory,  does  not  dilate  the  pupil,  paralyzes  the  vaso-motor  centres,  and  slows 
the  heart  even  after  the  vagus  has  been  paralyzed  with  atropine. 

THERAPEUTICS. — As  a  local  anaesthetic  eucaine  is  somewhat  less  powerful  than 
cocaine,  and  does  not  produce  primary  vaso-motor  constriction  nor  vaso-paralytic 
after-effects.  The  three  to  five  per  cent,  solution  will  rapidly  and  completely  anaes- 
thetize the  cornea  without  dilating  the  pupil  or  paralyzing  the  pupillary  reflexes.  The 
concentrations  and  dosage  of  the  solutions  generally  recommended  are  as  follows  -. 

The  strength  of  solution  may  vary  from  2  per  cent,  in  ophthalmology  to  10  per 
cent,  in  the  nose  and  throat. 

For  infiltration  anaesthesia  according  to  either  Schleich's  or  Braun's  method  i 
to  1000  up  to  0.3  Gm.  (5  grains)  ;  for  regional  analgesia  2  to  5  per  cent,  solution. 

The  influence  of  eucaine  upon  the  general  system  is  so  slight  that  fifteen  grains 
of  it  have  been  injected  hypodermically  (G.  W.  Spencer*)  without  the  production 
of  any  marked  symptoms.  It  may  prove  of  value  in  gastric  pain  or  vomiting.  The 
maximum  dose  is  said  to  be  three  grains. 

TROPACOCAINE— BENZOYL-TROPEIN. 

This  alkaloid  was  isolated  by  Giesel  from  the  narrow-leaved  coca-plant  of 
Java.  It  is  obtained  as  an  oily  liquid,  which  solidifies  in  radiating  crystals,  and  is 
soluble  in  chloroform,  ether,  or  benzin.  It  has  been  physiologically  studied  by 
Arthur  P.  Chadboume,  who  finds  that  locally  it  acts  in  a  manner  similar  to  cocaine, 
without,  however,  causing  ischaemia  or  congestion  of  the  mucous  membrane  with 
which  it  is  brought  in  contact.  It  was  found  by  Chadbourne  to  be  only  half  as 
toxic  as  cocaine.  In  lower  mammals  it  produces  in  sufficient  dose  loss  of  coordi- 


u8  GENERAL  REMEDIES. 

nation,  followed  by  violent  convulsions,  disturbances  of  the  respiration,  coma,  and 
death  by  centric  asphyxia.  The  convulsions  are  of  cerebral  origin.  Upon  the  cir- 
culation the  drug  seems  to  have  only  a  comparatively  feeble  influence,  causing, 
however,  when  in  sufficient  amount,  a  steady  fall  in  the  arterial  pressure.  The  tem- 
perature usually  begins  to  rise  before  the  convulsion,  and  has  been  noted  as  high  as 
4°  C.  above  the  normal.  When  tropacocaine  is  put  in  the  eye,  anaesthesia  is  said 
to  come  on  and  disappear  more  quickly  than  with  cocaine,  sensation  being  sus- 
pended in  less  than  half  a  minute  after  the  application  of  a  three  per  cent,  solution  : 
mydriasis  is  usually  absent,  never  very  pronounced. 

It  is  claimed  for  tropacocaine  that  it  is  especially  superior  to  cocaine  for  the  pro- 
duction of  spinal  anaesthesia,  being  very  much  less  apt  to  produce  fever  and  other 
disagreeable  symptoms  (K.  Schwarz5  and  F.  Neugebauer6).  According  to  Neu- 
gebauer,  0.05  to  0.06  gramme  of  the  alkaloid  may  be  injected. 

AN^ESTHESIN,  the  ethyl-ester  of  P-amido-benzoicacid,  a  white,  inodorous  pow- 
der, sparingly  soluble  in  cold  water,  whose  hydrochloride  makes  a  one  per  cent, 
solution,  which  is,  however,  so  irritant  that  when  used  hypodermically  it  produces  a 
burning  sensation,  and  should  therefore  be  diluted  before  injection.  In  the  experi- 
ments of  Binz,  colossal  doses  of  aneesthesin  given  to  rabbits  were  found  to  produce 
only  a  transient  methaemoglobinaemia ;  no  renal  irritation  or  methaemoglobinuria 
were  noted,  and  it  is  asserted  that  practically  ansesthesin  is  not  poisonous,  but  that 
it  is  a  very  active  local  anaesthetic. 

Anaesthesin  has  been  found  very  useful  in  painful  hemorrhoids,  three  to  seven 
grains  in  suppositories  ;  in  vesical  tenesmus,  especially  of  women,  in  soluble  bougies 
of  five  grains  ;  in  pruritus  vulvcz,  in  various  eczemas  with  great  irritation,  especially 
about  the  genitals,  a  ten  per  cent,  ointment  may  be  used. 

In  irritation  of  the  throat  and  palate,  lozenges  containing  from  three-tenths  to 
six-tenths  of  a  grain  are  stated  to  be  effective.  Internally,  anaesthesin  has  been  used 
in  gastrodynia  and  in  vomiting,  in  dose  of  from  five  to  seven  grains  (0.3-0.5  Gm.). 

Subcutin  is  white  crystalline  powder,  soluble  in  one  per  cent,  of  cold  water,  a 
compound  of  anaesthesin  and  paraphenol-sulphuric  acid,  introduced  by  Ritsert.7  It 
is  asserted  that  it  is  germicidal,  non-toxic,  and,  in  one  per  cent,  solution,  especially 
useful  for  the  production  of  infiltration-anaesthesia. 

ORTHOFORM  is  a  white  bulky  powder  very  slightly  soluble  in  water.  It  will 
not  produce  loss  of  sensation  through  the  skin  nor  mucous  membrane  but  is  an  effi- 
cient anaesthetic  when  applied  to  raw  surfaces.  As  it  also  possesses  some  antisep- 
tic power  it  is  used  chiefly  as  a  dusting  powder  to  burns  or  other  painful  wounds. 
In  gastric  ulcer  it  will  at  times  greatly  relieve  the  pain,  for  which  purpose  five  to 
ten  grains  (0.3-0.6  Gm.)  may  be  given  at  a  dose.  It  is  of  great  service  in  alleviat- 
ing pain  in  tuberculous  laryngitis. 

STOVAINE. — This  benzoyl  derivative  was  brought  forward  by  Tourneau  as  being 
less  toxic  than  cocaine.  It  has  been  used  in  spinal  analgesia  by  Tuffier18  who 
asserts  that  it  is  not  followed  by  unpleasant  after  symptoms.  He  injected  one-half 
c.c.  (7  minims)  of  a  10  per  cent,  solution.  It  should  not  be  used  in  connection 
with  adrenalin. 

ALYPIN. — The  benzoyl-tetramethyl-diamino-ethyl-dimethyl  carbinol,  suggested 
by  Impens,19  is  a  crystalline  soluble  powder  not  decomposed  by  boiling  nor  precipi- 
tated by  moderate  quantities  of  sodium  bicarbonate.  It  seems  to  be  much  less 
toxic  than  cocaine  and  equally  active  as  an  anaesthetic,  and  differs  from  that  alka- 
loid in  not  dilating  the  pupil  nor  affecting  accommodation.  It  produces  vascular 
dilatation  instead  of  contraction.  About  the  eye  a  2  to  4  per  cent,  solution  may  be 
employed  but  in  the  nose  and  throat  Seifert  *°  recommends  a  10  per  cent,  strength. 


ANESTHETICS.  119 

NIRVANIN. — Di  -  ethyl -glycocyl-para-amido  •  ortho-oxy  -  benzole  acid-  methyl- 
ester-hydrochloride. — Introduced  into  practical  medicine  by  A.  Einhorn  and  R. 
Heinz.15  This  substance  is  readily  soluble  in  water  and  is  a  pronounced  local  anaes- 
thetic, but,  according  to  reports,  not  equal  in  activity  to  cocaine.  A.  Luxenburger,16 
as  the  result  of  experimental  research,  concludes  that  it  is  so  much  less  poisonous 
than  cocaine  that  a  two  per  cent,  solution  is  very  effective  and  may  be  freely  used 
for  the  production  of  infiltration-anaesthesia.  According  to  the  same  authority,  the 
maximum  amount  of  nirvanin  to  use  is  eight  grains  (0.55  Gm.). 

PRACTICAL  LOCAL  ANAESTHESIA. — If  it  were  possible  to  prevent  the 
absorption  of  one  of  the  active  local  anaesthetics  after  its  injection  into  a 
tissue  for  a  sufficient  length  of  time,  the  method  of  local  anaesthesia  would 
be  applicable  to  a  very  large  proportion  of  surgical  operations.  When, 
as  in  the  case  of  a  felon,  the  part  to  be  operated  on  can  be  tightly  sur- 
rounded by  a  constricting  bandage,  so  as  to  almost  entirely  shut  off  circu- 
lation, it  is  very  easy  to  inject  a  local  anaesthetic  and  afterwards  to  operate 
without  the  production  of  pain.  Rarely,  however,  is  the  surgical  task  so 
easy,  and  the  several  processes  discussed  below  have  been  invented  for 
the  purpose  of  overcoming  the  practical  difficulties. 

Infiltration- Anessthesia. — In  this  process,  as  devised  by  Schleich,  the 
original  attempt  was  to  increase  the  activity  of  cocaine  by  adding  to  its 
benumbing  power  the  influence  of  the  interference  with  the  circulation 
of  the  part,  and  of  pressure  upon  the  nerve-trunks  of  the  part,  produced 
by  the  injection  of  large  quantities  of  water  directly  into  the  tissue  to  be 
operated  on.  In  this  process,  as  originally  devised,  the  skin  having  been 
frozen  by  means  of  an  ethyl  spray,  the  point  of  a  large  hypodermic 
syringe  is  thrust  into  its  papillary  layer  and  a  small  mass  of  the  fluid  is 
injected,  not  under,  but  into,  the  skin.  The  needle  of  the  syringe  is  then 
pressed  in  a  little  deeper  and  a  new  injection  made,  the  process  being  con- 
tinued until  a  sufficient  depth  is  reached.  This  method  has  been  applied 
not  only  in  minor  but  also  in  major  surgery.  During  a  large  operation 
it  may  be  necessary  to  repeat  from  time  to  time  as  the  knife  of  the  sur- 
geon cuts  more  and  more  deeply  into  the  tissues. 

Three  solutions  were  used  by  Schleich.  No.  i,  of  medium  strength,  may  be 
made  by  dissolving  at  the  time  of  using  a  powder  composed  of  one  and  a  half 
grains  of  cocaine  hydrochlorate,  one-third  of  a  grain  of  morphine  hydrochlorate, 
and  three  grains  of  common  salt  in  twenty-seven  drachms  of  sterilized  water.  No. 
2,  the  weakest  solution,  contains  only  one-tenth  the  percentage  of  cocaine  in  No.  i ; 
whilst  No.  3,  the  strongest  solution,  contains  double  the  percentage.  No.  3  is  used 
only  when  there  is  an  active  inflammatory  lesion  of  moderate  extent,  as  in  case  of 
a  furuncle.  In  many  cases  it  is  essential  that  not  only  the  part  to  be  opened  but 
the  tissues  beneath  it  be  infiltrated.  Thus,  a  furuncle  or  abscess  may  be  completely 
encompassed  with  a  zone  of  artificial  oedema. 

A  most  important  modification  of  the  method  of  Schleich' s  infiltration- 
anaesthesia  has  been  brought  to  the  notice  of  the  profession  by  its  inventor, 
H.  Braun,8  who  found  that  if,  by  local  cooling,  the  vitality  and  circulation 
of  a  tissue  be  interfered  with,  absorption  of  the  injected  cocaine  will  be  so 


120 


GENERAL  REMEDIES. 


long  delayed  that  the  symptoms  of  poisoning  will  be  put  off  almost  indefi- 
nitely or  may  fail  to  develop  at  all.  Acting  upon  this  knowledge,  Braun 
obtained  from  the  conjoint  use  of  adrenalin  and  cocaine  such  satisfactory 
results  as  to  apparently  open  a  new  field  for  the  use  of  local  anaesthesia  : 
by  employing  a  one  to  five  per  cent,  solution  of  cocaine  to  which  had 
been  added  from  i  :  10,000  to  i  :  100,000  of  adrenalin,  and  beginning 
the  operation  from  one  to  one  and  a  half  hours  after  the  injection,  he  was 
enabled  to  do  trunkal  operations  without  causing  suffering. 

FIG.  6. 


Showing  mode  of  injecting  the  fluid  under  an  abscess  in  successive  whorls.    (Schleich.) 

FIG.  7. 


Showing  the  syringe-point  in  the  papillary  layer  of  the  skin. 


Braun' s  method  for  the  production  of  local  anaesthesia  has  been  fol- 
lowed by  so  much  of  success  by  various  surgeons  *  that  it  would  seem  to 
be  demonstrated  that  adrenalin,  by  its  powerful  constringing  influence 
upon  the  blood-vessels,  not  only  very  sensibly  increases  the  benumbing 
action  of  the  local  anaesthetic,  but  also,  by  lessening  the  rate  of  the  absorp- 
tion of  the  drug,  greatly  increases  the  duration  of  its  local  activity.  The 
further  suggestion  of  A.  E.  J.  Barker,9  that  the  conjoint  use  of  beta-eucaine 
and  adrenalin  affords  a  most  excellent  method  of  producing  infiltration- 
anaesthesia,  has  been  followed  out  in  Philadelphia  by  various  surgeons 
with  great  satisfaction.  The  plan  may  be  readily  carried  out  by  the  fol- 
lowing method  : 

Powders  containing  three  grains  (o.  2  Gm. )  of  beta-eucaine  and  twelve 
grains  (o.  8  Gm. )  of  pure  sodium  chloride  are  to  be  kept  on  hand  by  the 
surgeon.  At  the  time  of  operation,  one  such  powder  is  added  to  100  c.c. 
of  boiling  distilled  water,  which  is  allowed  to  cool,  and  i  c.c.  of  adre- 
nalin chloride  solution  (i  :  1000)  is  added,  so  that  100  c.c.  of  the  resulting 

*  See  Braun,  Cb.  C.,  1903;  Honigman,  Ibid.;  Gangitans,  B.  M.  /.,  1903,  ii. ;  Lef- 
mann,  M.  M.  W.,  1902;  Braun,  A.  K.  C.,  Bd.  Ixix. 


ANESTHETICS.  121 

liquid  contain  twelve  grains  of  beta-eucaine  and  0.015  grain  of  adrenalin 
chloride.  The  whole  100  c.c.  may  be  used  at  one  infiltration-anaesthesia, 
but,  according  to  Barker,  from  50  to  60  c.c.  usually  suffice,  even  in 
such  considerable  operations  as  for  the  cure  of  hernia,  castration,  etc. 
It  is  of  course  essential  that  an  aseptic  syringe  be  employed,  and  the 
needle  should  be  of  platinum  with  iridium  point,  so  that  it  can  be  dis- 
infected in  the  flame  of  an  alcohol  lamp  immediately  before  use. 

In  his  original  discussion  of  infiltration-anaesthesia,  Schleich  recog- 
nized that  it  was  possible  to  produce  a  transitory  anaesthesia  by  infiltra- 
tion with  pure  water,  and  it  has  been  shown  by  S.  G.  Gant17  that  in 
cases  of  superficial  abscesses  and  other  surgical  diseases,  and  in  situations 
in  which  injected  water  will  for  the  time  being,  as  it  were,  be  dammed 
up  in  the  tissues,  it  is  possible  to  do  painless  minor  operations  by  simply 
throwing  sterile  water  into  the  parts  in  such  amounts  as  to  produce  great 
distention.  The  technique  of  the  method  is  as  follows  :  A  fold  of  the 
skin  on  one  end  of  the  line  of  the  incision  is  compressed  between  the 
thumb  and  forefinger,  and  then  has  slowly  injected  into  it  a  few  drops  of 
water  so  as  to  produce  a  small,  localized,  blister-like  distention.  This  is 
repeated  until  the  whole  line  of  incision  has  been  gradually  injected  with 
water  into,  not  under,  the  skin.  The  needle  is  then  plunged  through 
this  distended  line,  and  subcutaneous  injections  are  rapidly  made  until  a 
firm,  whitish,  ridge-like  swelling  is  produced,  through  which  the  incision 
can  usually  be  made  without  pain. 

The  method  seems  to  be  especially  applicable  to  rectal  diseases.  In 
external  thrombotic  hemorrhoids  the  water  should  be  injected  between 
the  layers  of  the  skin  overlying  the  clot ;  in  cutaneous  hemorrhoids  both 
the  skin  and  the  tumor  should  be  distended  tightly  ;  in  external  hemor- 
rhoids each  tumor  must  be  distended  so  tightly  as  to  cause  it  to  turn 
white.  In  rectal  operations  the  skin  and  subcutaneous  structure  up  to 
the  anal  margin,  then  the  mucosa  and  submucosa,  the  external  and,  if 
necessary,  the  internal  sphincter  muscle,  must  be  distended  with  water 
slowly  injected.  In  deep  rectal  operations,  involving  extensive  cutting  or 
curetting,  water  anaesthesia  seems  not  to  suffice. 

Centric  Local  Anesthesia. — Corning,  A.  Bier,10  Seldowitsch,11  and 
Tuffier 12  introduced  into  the  practice  of  surgery  the  injection  of  cocaine 
into  the  spinal  canal  for  the  production  of  wide-spread  anaesthesia  below 
the  point  of  injection,  and  the  method  has  been  successfully  employed,  so 
far  as  the  absence  of  pain  is  concerned,  by  various  surgeons  in  a  large 
number  of  major  operations  in  the  lower  portions  of  the  body.  Experi- 
ence has,  however,  shown  that  this  method  is  attended  by  so  much  diffi- 
culty and  danger  that  it  has  almost  passed  out  of  vogue. 

In  performing  the  operation  the  hollow  needle  is  introduced  into  the  vertebral 
canal,  as  in  the  operation  of  lumbar  puncture,  and  from  one-sixth  to  one-third  of  a 
grain  of  cocaine  is  injected,  the  most  absolute  antiseptic  precautions  being  taken 
throughout.  Loss  of  sensation  in  the  lower  extremities  is  usually  complete  in  ten 
minutes  and  begins  to  go  off  in  about  an  hour.  Serious  nervous  disturbances  have 


122  GENERAL  REMEDIES. 

been  present  in  a  large  proportion  of  the  cases  and  fatal  results  have  been  frequent 
One  surgeon  reported  five  deaths  in  one  hundred  intraspinal  injections  ;  and,  ac- 
cording to  H.  Mohr-Bielefeld,13  all  available  statistics  taken  together  show  that  one 
death  is  to  be  expected  in  every  two  hundred  spinal  anaesthesias. 

Much  more  available  for  the  purposes  of  practical  surgery  than  is  cen- 
tric anaesthesia  is  the  process  which  may  be  known  as  Neural  Anesthesia, 
As  long  ago  as  1884  the  injection  of  cocaine  into  a  nerve-trunk  for  the 
purpose  of  producing  anaesthesia  in  the  region  supplied  by  the  nerve  was 
suggested,  not  very  clearly,  by  Hall  and  Halstead.11  In  the  production 
of  neural  anaesthesia  cocaine  has  been  almost  universally  employed  by 
surgeons,  but  whether  it  has  or  has  not  superiority  over  eucaine  has  not 
as  yet  been  determined.  The  selected  local  anaesthetic  is  to  be  injected 
immediately  in  contact  with  the  nerve,  if  it  be  a  small  one,  or  into  the 
nerve-trunk  itself  if  the  nerve  be  large.  So  injected,  cocaine  produces  a 
complete  break  in  the  conducting  power  of  the  nerve,  affecting,  it  is 
affirmed,  not  only  the  fibres  which  are  connected  with  the  pain  sense,  but 
all  afferent  fibres,  so  that,  when  the  incision  is  made  into  the  region  of  the 
peripheral  distribution  of  the  nerve,  not  only  is  there  no  pain,  but  no  sur-- 
gical  shock,  all  nervous  impulses  going  upward  from  the  lower  part 
operated  upon  being  shut  off  from  the  nerve-centres.  When  the  nerve  is 
small  and  easily  reached,  the  injection  of  a  two  per  cent,  solution  of 
cocaine  may  be  made  into  its  sheath  without  previous  incision  ;  but  when 
an  amputation  or  other  large  operation  is  to  be  performed,  it  is  essential 
to  expose  under  infiltration-anaesthesia  the  one  or  more  nerves  involved, 
and  inject  a  solution  of  cocaine,  which  should  not  be  stronger  than  one 
per  cent. ,  directly  into  the  centre  of  the  nerve.  When  neural  anaesthesia 
is  practised,  it  is  essential  that  the  most  absolute  antiseptic  precautions 
be  taken.  A  priori,  it  might  be  expected  that  the  process  would  involve 
the  danger  of  the  production  of  neuritis,  but  so  far  the  clinical  reports  do 
not  indicate  that  such  danger  exists. 


REFERENCES. 

ANAESTHETICS.  14   CARTWRIGHT   .  .  Lancet,  1876,  689. 

i.  NEUDORFAN  .  .  .  B.  M.  J.,  1896,  i.  J5   QTTLEY Lancet,  1883,  i.  95. 

NITROUS  OXIDE.  j6.  THOMSON  and  KEMP  .  N.  Y.  M.  R.,  1898,  ii. 

i.  HERMANN  .  .  .  .  A.  A.  and  P.,  1864.  17.  WOOD T.  G.,  Aug.  1890. 

a.  JOLYET  and  BLANCHE  .  A.  de  P.,  July,  1873.  18.  LE  BRETON   .  .  .  P.  M.  J.,  1902,  ix.  586. 

3.  COLTON The  Physiological  Action 

of    Nitrous    Oxide   Gas,  ETHER. 

Philadelphia,  1871.  i.  KRATSCHMER   .   .  W.  A.  W.,  1870,  Abt.  ii. 

4.  THOMSON    ....  P.  M.  T.,  Nov.  15, 1873.  2.  HARE U.  M.  M.,  i.  419. 

5.  WOOD Dental  Cosmos,  May,  1893.         3.  KNOLL W.  A.  W.,  Oct.  1876. 

6.  MACMUNN.  .  .   .  The  Spectroscope  in  Medi-         4-  KRONECKER  .   .   .  C.  B.  S.  A.,  1890. 

cine,  London,  1880.  5.  EULENBERG  .  .  .  H.  S.  Jb.,  1883,  117. 

7.  AMORY N.  Y.  M.  J.,  Aug.  1870.  6.  BERNARD    ....  Prog.  M.,  1876,  77. 

8.  GOLDSTEIN    .  .   .  A.  G.  P.,  xvii.  7-  WOOD U.  M.  M.,  July,  1898. 

9.  VAN  ARSDALE  .  .  A.  J.  M.  S.,  cii.  8.  FLOURENS  .  .  .   .  C.  R.  S.  B.,  1847,  xxiv.  161 

10.  HEWITT M.  C.  Tr.,  Ixxxii.  et  at. 

11.  KEMP B.  M.  J.,  1897,  ii.  9-  LONGET A.  G.  M.,  4  s.,  xiii.  374. 

12.  MACMUNN.   .  .  .  D.  J.  M.  S.,  1879,  210.  10.  WALLER B.  M.  J.,  Nov.  20,  1897. 

13.  BUXTON Trans.    Odontol.    Soc.    of  ii.  CONLY C.  R.  S.  B.,  Feb.  13,  1876. 

Great  Britain,  1887,  xix.  12.  LOCKE J.  Ex.  M.,  1896,  i. 


ANESTHETICS. 


123 


REFERENCES.—  Continued. 


13.  SANSOM Chloroform,  Phila.,  1866. 

14.  BOWDITCH  and  MINOT  .  B.  M.  S.  J.,  May,  1874. 

15.  WITTICH    .  .   .   .  S.  Jb.,  cxlii.  212. 

16.  SCHMIDT    .  .   .  .  V.  A.  P.  A.,  1864,  xxix.  19. 

17.  SERRES A.  G.  M.,  4  s.,  xiii.  433. 

18.  WRIGHT J.  P.,  1901,  xxvi.  30. 

CHLOROFORM. 

1.  BENEDICENTI   .  .  G.  A.  M.  T.,  1895,  378. 

2.  SIOLFATTI  ....  Rif.  M.,  1895,  i.  591. 

3.  ZKLLER Z.  P.  C.,  viii.  74. 

4.  SABARTH     ....  Das     Chloroform,    Wiirz- 

burg,  1866. 

5.  NOEL L.  M.  R.,  1877,  457. 

6.  SIMONIN Cb.  C.,  1877,  234. 

7.  WOOD U.  M.  M.,  July,  1898. 

8.  BERT    .  .   .  .   .   .  C.  R.  S.  B.,  1867,  Ixiv. 

9.  BERNSTEIN    .   .   .  S.  Jb.,  cxlii.  227. 

10.  ENGLISH  CHLOROFORM  COMMITTEE  .  Proc. 

Royal  Med.  Chir.  Soc., 
London,  xlviii.  326. 

11.  GASKELL  and  SHORE  .  B.  M.  J.,  1893,  i. 

12.  BOWDITCH  and  MINOT  .  B.  M.  S.  J.,  1874. 

13.  Ed.  M.  J.,  1842. 

14.  J.  A.  and  P.,  xiii.  226. 

15.  MACWILLIAM  .   .  B.  M.  J.,  1890,  ii. 

16.  BERT J.  del'A.  and  P.,  May,  1870. 

17.  BERT C.  R.  S.  B.,  July,  1885. 

18.  ST .-MARTIN  ...  La  Respiration,  Paris,  1893. 

19.  HARLEY P.  P.  S.  L.,  1865. 

20.  BOETTCHER  .  .   .  V.  A.  P.  A.,  xxxii.  126. 

21.  SCHMIDT  and  SCHWEIGER-SEIDEL  .  Bericht. 

d.  konigl.  sachs.  Gesell. 
d.  Wissensch.,  math.- 
phys.  Kl.,  1867,  190. 

22.  KAPPELER  .  .  .  .  A.  K.  C.,  1887,  xxxi. 

23.  BERNSTEIN    .   .  .  U.  N.  M.  T.,  1870. 

24.  LEYDEN Beitr.  z.  Path.  d.  Icterus, 

Berlin,  1866. 

25.  NOTHNAGEL  .   .  .  B.  K.  W.,  i866. 

26.  HUSEMANN    .   .   .  S.  Jb.,  cli.  84. 

27.  KAPPBLER  ....  Die    Anaesthetica,    Stutt- 

gart, 1880. 
Z.  P.  C.,  viii. 
V.  A.  P.  A.,  cxv. 
C.  M.  W.,  1888. 
Fort.  M.,  1891,  ix. 
V.  A.  P.  A.,  1892,  cxxx. 
B.  M.  J.,  1882,  i.  776. 
An.  d'H.,  Jan.  1874. 
E.G.  T.,  xciii.  433. 
N.  Y.  M.  R.,  July  11,1885. 
.  J.  A.   M.  A.,  1901,  xxxvi. 
1409. 

38.  BLAUEL B.  K.  C.,  1901,  xxxi.  271. 

39.  TUNNICLIFFE  and  ROSBNHEIM  .  P.  P.  S.  L., 

1903. 

40.  EMBLEY  .      .  .  .  B.  M.  J.,  1902. 

41.  KRUGER Z.  C.  P.  P.,  1902,  iii. 

42.  SHERRINCTON  and  SOWTON  .  B.  M.  J.  Supp., 

1903,  ii. 

ETHYL   CHLORIDE. 

1.  WOOD  and  CERNA  .  Tr.  P.  C.  M.  S.,  1892. 

2.  LEBET In.  Diss.,  Berne,  1901. 

3.  MALHERBE  and  ROUBINOVITCH  .  B.  M.,  June, 

1902. 

4-  WARE N.  Y.  M.  R.,  1901,  lix. 

5.  ALLEN A.  J.  M.  S.,  Dec.  1903. 


6.   GlFFORD 


.  B.  M.  J.  July  8,  1905. 


28.  SOKOLOVSKI  .  . 

.  Z. 

29.  STRASSMANN  . 

.  V. 

30.  STRASSMANN  . 

.C. 

31.  SALKOWSKI  .  . 

.F< 

32.  BERTELS.  .  .  . 

.  V. 

33- 

B. 

34.  DOLBEAU  .  .  . 

.  Ai 

35- 

B. 

36. 

N. 

37.  PAUGH  

•  J. 

ETHYL   BROMIDE. 

1.  Th.  M.,  1889,  iii. 

2.  T.  G.,  viii. 

3.  GILLES B.  K.  W.,  1892,  xxix. 

4.  THORNTON  and  MAXWELL  .  T.  G.,  1892. 

5.  ABONYI Wiener  Klinik.,  1891,  No.  i. 

6.  GLEICH W.  K.  W.,  1892,  v. 

7.  SUAREZ  DE  MENDOZA  .  B.  A.  M.,  1894. 

8.  REICH Th.  M.,  1893. 

9.  FLATTEN    .  .  .   .  Z.  Mb.,  1897,  No.  7. 

10.  WOOD P.  M.  T.,  1879-80,  x. 

11.  GINSBURG  ....  In.  Dis.,  St.  Petersburg. 

12.  COLE B.  M.,  1903,  i. 

PENTAL. 

1.  PHILIPP A.  K.  C.,  1892,  xlv. 

2.  CERNA Trans.  Texas  State  Med. 

Ass.,  1893. 

3.  GURLT     A.-K.  C.,  1893,  xlvi. 

METHYLENE  BICHLORIDE. 

1.  RICHARDSON     .  .  M.  T.  G.,  1867,  478. 

2.  B.  M.  J.,  1883,  ii.  104. 

PRACTICAL  ANAESTHESIA. 

1.  COATS Gl.  M.  J.,  xxxiv.  323. 

2.  GOULD M.  News,  Oct.  1892. 

3.  GARREE B.  K.  Ch.,  1894,  xi. 

4.  GURLT     .  .'.  .  .  A.  K.  C.,  Iv.  473. 

5.  EVANS N.  Y.  M.  R.,  1897,  i. 

6.  MACWILLIAM  .  .  B.  M.  J.,  1890,  ii. 

7.  LANCET  COMMISSION  .  Lancet,  1893,  i. 

8.  WOOD  and  CARTER  .  J.  Ex.  M.,  1892,  ii. 

9.  HOLSCHER     .  .   .  A.  K.  C.,  1898,  Ivii. 

10.  BECKER V.  A.  P.  A.,  1895,  cxl. 

11.  DUMERIL  and  DEMARQUAY  .  A.  G.  M.,  1848, 

2  s.  xvi. 

12.  BOUISSON    ....  Trait6    th6orique   et    pra- 

tique    de     la    Methode 
anesthdsique,  Paris,  1850. 

13.  SULZYNSKI     .  .  .In.  Dis.,  Dorpat,  1865. 

14.  SCHEINSON    ...  A.  Hk.,  1869. 

15.  DUBOIS Prog.  M.,  1883,  xi.  951. 

16.  HOLMES Chi.  M.  J.,  Sept.  1868. 

17.  PRINCE N.  Y.  M.  R.,  1892. 

18.  GOMBERG   .  .  .   .  D.  Z.  Ch.,  xxxix. 

19.  PATH P.  M.  C.  P.,  1887. 

20.  STRASSMANN    .  .  V.  A.  P.  A.,  cxv. 

21.  OSTERTAG  .   .  .  .  V.  A.  P.  A.,  cxviii. 

22.  KAST  and  MESTER  .  Z.  K.  M.,  1891,  xviii. 

23.  TEDESCHI  .  .  .  .  Cl.  M.,  1897,  iii. 

24.  BOTSCHAROFF  .  .  In.  Diss.,  Kiew,  1893. 

25.  FRAENKEL     .  .  .  V.  A.  P.  A.,  cxxvii.,cxxix. 

26.  BANDLER    .  .  .  .  S.  Jb.,  cclii. 

27.  AMBROSIUS    .  .  .  V.  A.  P.  A.,  Suppl.  1895. 

28.  SCHENCK    ...     Z.  Hk.,  1898. 

29.  EISENDRATH          Chicago  Med.  Rep.,  1896,  x. 

30.  DESGREZ  and  NICLOUX  .  C.  R.  S.  B.,  1898, 

274. 

31.  PRUS     W.  K.  W.,  1900. 

32.  KEEN T.  G.,  1904. 

33.  GUTHRIE     .   .   .   .  L.  L.,  1903,  ii. 

34.  WOOD Trans.  International  Med. 

Congress,  Berlin,  1881. 

35.  SCHMIDT    .  .  .  .  A.  A.  P.,  1897. 

36.  OFFERGELD   .  .   .  A.  K.  C.  1904,  Ixxv,  758. 

37.  CARMICHAKL  and  BEATTIE  .  Lancet,  Aug.  12, 

1905- 


124 


GENERAL  REMEDIES. 


REFERENCES.—  Continued. 

38.  SriLESand  MACDONALD  .  Scot.  Med.Surg.J.  8. 

Aug.  1904,  p.  97.  9. 

39.  MULI-EK A.  K.  C.  1905,  Ixxv,  896.  10. 

40.  BRACHETT  STONE  and  Low  .  B.  M.  S.  J.  cli,  n. 

p.  2  12. 

41.  SENCERT    .   .   .   .  C.  R.  S.  B.  1905,  Iviii,  1080.  13. 

14. 
LOCAL   ANAESTHESIA. 

1.  VINCI Th.  M.,  June,  1896.  15. 

2.  VINCI A.  I.  B.,  1899,  xxxi.  32.  16. 

3.  VER  EECKE  .   .   .  B.  A.  R.  B.,  1897,  x.  i. 

4.  SPENCER     .  .  .   .  U.  M.  M.,  1896.  17- 

5.  SCHWARZ    .  .   .   .  M.  M.  W.,  1902,  xlix.  18. 

6.  NEUGEBAUER    .  .  W.  K.  W.,  1901,  xiv.  19. 

7.  RITSERT S.  J.,  Bd.  cclxxix.  20. 


BRAUN A.  K.  C.,  1903,  Ixix. 

BARKER L.  L.,  July,  1903. 

BIER D.  Z.  Ch.,  li.  3. 

SELDOWITSCH  .  .  Ch.  C.,  1899,  xxvi.  mo. 
TUFFIER     ....  P.  M.  J.,  Dec.  1899. 

MOHR-BlELEFELD  .  M.  W.,   1902. 

HALL  and   HALSTEAD  .  N.  Y.  M.  J.,  Dec. 

1884. 
EINHORN  and  HEINZ    .   .  M.  M.  W.,  xlviii. 

LUXENBURGER       .  M.   M.  W.,   1899;    P.   M.  J., 

July,  1899. 

GANT N.  Y.  M.  J.,  Jan.  1904. 

TUFFIER    .  .   .   .  W.  K.  W.  1905,  377 

IMPENS D.  M.  W.  1905,  xxxi,  1154. 

SEIFERT     .   .   .   .  D.  M.  W.  xxxi,  1352. 


FAMILY   III.— SOMNIFACIENTS. 


IN  the  family  somnifacients  are  placed  in  this  treatise  those  drugs 
whose  chief  use  in  practical  medicine  is  for  the  production  of  sleep. 
Hyoscine  is  a  valuable  hypnotic,  but  as  it  is  found  in  plants  associated 
with  the  delirifacient  alkaloids,  and  is  physiologically  more  closely  allied 
to  them  than  to  the  opium  alkaloids,  it  will  be  considered  under  the  head  of 
Delirifacients. 

OPIUM.     U.S. 

The  inspissated  juice  of  the  unripe  capsules  of  the  Papaver  somni- 
ferum,  or  poppy.  It  is  obtained  by  incising  the  capsules  with  a  small, 
sharp  knife,  and  twenty-four  hours  afterwards  scraping  off  the  exuded 
juice  with  a  blunt  blade.  Opium  is  produced  in  various  parts  of  the 
world, — chiefly  in  Turkey,  Asia  Minor,  Persia,  and  India,  but  also  to  a 
very  slight  extent  in  England,  Germany,  and  the  United  States.  Our 
market  is  almost  exclusively  supplied  from  Asia  Minor,  with  the  variety 
known  as  Smyrna  or  Turkey  Opium.  This  occurs  in  masses  from  the 
size  of  the  fist  to  that  of  a  child's  head,  irregularly  globular,  more  or 
less  flattened,  covered  externally  with  the  capsules  of  a  species  of 
Rumex  or  dock,  hard  externally,  softer  and  of  a  reddish-brown  color 
within,  and  of  a  strong  narcotic  odor  and  taste. 

On  exposure  to  the  air,  opium  becomes  hard  and  brittle,  and  is 
readily  reduced  to  a  powder  of  a  yellowish-brown  color.  It  yields  its 
principles  to  water,  alcohol,  and  diluted  acids,  forming  dark  brown  solu- 
tions. It  is  a  very  complex  body,  containing  the  alkaloids  morphine, 
codeine,  narceine,  narcotine,  thebaine,  papaverine,  porphyroxine,  crypto- 
pine,  meconine,  opianine,  and  paramorphine,  besides  meconic,  thebolactic, 
and  sulphuric  acids,  extractive  matter,  gum,  glucose,  fixed  oils,  a  volatile 
odorous  principle,  and  other  substances  of  no  importance. 

Local  Action. — The  local  action  of  opium  and  its  chief  alkaloid  ap- 
pears to  be  purely  sedative. 

Elimination. — After  its  absorption  morphine  probably  passes  into  all 
the  secretions  ;  after  its  hypodermic  administration  it  has  been  detected 
in  the  gastric  juice  by  Orlt,1  and  in  the  saliva  by  Rosenthal,*  but  it 
largely  escapes  with  the  urine,  in  which  it  has  been  found  by  Hilger 
( quoted  by  Gscheidlen),  Bouchardat,3  Lefort,*  Kausmann,5  Eliasson,6  and 
Wormley.7  According  to  Faust,11  the  most  important  channel  of  elimina- 

125 


126  GENERAL   REMEDIES. 

tion  is  the  alimentary  tract ;  it  is  to  some  extent  excreted  by  the  salivary 
glands  as  well  as  the  mucous  membrane  of  the  stomach  and  bowels,  to 
be  probably  reabsorbed.  This  has  been  proved  not  only  by  experiments 
upon  animals  in  which  the  morphine  was  injected  subcutaneously,  but 
also  in  the  human  individual  (Rosenthal,8  P.  Binet,9  Hamburger10). 
Elimination  probably  goes  on  slowly,  as  Wormley  detected  the  alkaloid 
in  urine  passed  three  days  after  its  ingestion,  and  in  habitual  opium-eaters 
morphine  may  be  present  in  the  urine  seven  days  after  the  cessation  of  the 
habit.11  A.  Antheaume  and  A.  Mouneyrat 12  detected  morphine  in  the 
body  of  an  opium-eater  who  had  died  fourteen  days  after  the  last  dose. 
It  was  found  most  abundantly  in  the  liver,  next  in  the  brain,  next  in  the 
kidneys. 

Without  doubt  a  considerable  portion  of  morphine  escapes  from  the  body  un- 
changed, but,  according  to  Cloetta,59  from  fifty  to  seventy  per  cent,  is  destroyed  in 
the  body.  The  theory  advanced  by  E.  S.  Faust,13  that  the  immunity  produced  by 
the  habitual  use  is  due  to  increased  power  of  the  body  to  destroy  morphine,  has 
been  shown  by  Cloetta,  however,  to  be  untrue. 

PHYSIOLOGICAL  ACTION. — When  opium  is  taken  in  such  dose  as  to 
produce  its  mildest  physiological  effects,  it  exerts  a  quieting  influence, 
inducing  a  peculiar  dreamy  condition  of  bodily  comfort  and  happy  con- 
tent, during  which  images  and  ideas  float  before  the  mind,  and  by  their 
endless  and  effortless  repetition  shorten  the  time,  which  seems  to  lose 
itself  in  rest.  It  is  commonly  asserted  that  there  is  a  stage  of  the  action 
of  opium  in  which  the  activity  of  the  mental  faculties  is  exalted.  This 
may  be  so  in  some  persons,  and  especially  in  those  who  have  accustomed 
themselves  to  the  use  of  the  drug  as  a  stimulant ;  but  our  experience  is 
that  in  those  who  do  not  habitually  take  opium  true  mental  power  is, 
during  all  the  stages  of  the  action  of  the  drug,  diminished  rather  than  in- 
creased. The  state  induced  is  the  fabled  calm  of  the  lotus-eater  rather 
than  the  energetic  activity  of  production.  Even  in  those  who  are  accus- 
tomed to  the  use  of  opium  as  an  aid  to  work,  it  is  probable  that  the  imagi- 
nation rather  than  the  reasoning  faculty  is  excited  by  it.  After  a  length 
of  time,  varying  according  to  the  idiosyncrasies  of  the  patient  and  the  dose 
of  the  drug,  the  condition  which  has  been  noted  gradually  passes  into 
sleep, — either  light  and  dreaming,  or  natural,  or  heavy  and  deepening 
into  stupor,  according  to  the  amount  of  the  drug  ingested.  On  awaken- 
ing, the  patient  may  return  at  once  to  his  normal  condition,  but  very 
often  he  experiences  a  state  of  depression,  as  shown  by  languor,  a  little 
headache,  nausea,  or  even  vomiting,  which  may  last  for  some  hours. 

After  very  large  doses,  the  first  stage  of  the  action  of  opium  is  very 
short,  or  it  may  be  entirely  wanting,  sleep  coming  on  almost  at  once. 
Thus,  we  have  seen  deep  coma  produced  in  three  minutes  by  a  hypo- 
dermic injection  of  morphine.  The  symptoms  of  the  second  stage  of 
opium -poisoning  closely  resemble  those  of  congestion  of  the  brain  :  the 
pupils  are  strongly  contracted  ;  the  face  is  more  or  less  suffused,  often 


SOMNIFACIENTS.  127 

deeply  cyanosed  ;  the  pulse  full,  slow  and  strong  ;  the  skin  generally 
dry  and  warm  ;  the  respiration  slow  and  deep,  and,  it  may  be,  sterto- 
rous ;  unconsciousness  is  apparently  complete,  though  generally  the  sub- 
ject can  be  aroused  by  violent  shaking  or  by  shouting  in  his  ear,  but 
relapses  at  once  when  left  to  himself.  When  the  patient  is  aroused,  the 
respirations  become  more  rapid,  and  the  skin  often  regains  almost  at 
once  its  normal  color.  Death  very  rarely  occurs  during  this  second 
stage  of  opium-poisoning.  When  the  symptoms  do  not  gradually  amel' 
iorate,  the  third  stage,  that  of  prostration,  is  developed.  The  coma  is 
now  profound,  and  to  arouse  the  patient  may  be  impossible  ;  the  pupils 
are  absolutely  contracted  or,  as  death  approaches,  are  widely  dilated  ; 
the  respirations  are  distant,  slow,  feeble,  and  imperfect,  and  often  inter- 
rupted by  intervals  of  death-like  quiet ;  the  countenance  is  at  once  pallid 
and  cyanosed  ;  the  pulse  continually  grows  more  rapid  and  more  feeble  ; 
the  cold  and  moist  skin  finally  becomes  covered  with  a  clammy  sweat. 
Even  yet  the  patient  may  recover j  the  return  to  life  being  very  gradual  ; 
when  death  occurs,  it  is  by  failure  of  the  respiration,  but  amid  an  almost 
complete  extinguishment  of  the  vital  functions. 

Although  the  symptoms  which  have  been  narrated  are  those  usually 
produced  by  opium,  yet  in  certain  individuals  the  drug  provokes  quite 
different  phenomena.  Thus,  not  infrequently  there  is  an  excessive  de- 
pression following  the  opiate  sleep.  This  state  is  seen  most  frequently 
in  neuralgic  or  neuropathic  females.  The  symptoms  are  a  feeling  of 
weakness  and  prostration,  often  accompanied  by  chilliness,  dull  headache, 
and  giddiness,  but  especially  marked  by  intense  nausea  and  repeated  vomit- 
ing. Very  frequently  vomiting  does  not  take  place  so  long  as  absolute 
rest  in  the  horizontal  position  is  maintained  :  indeed,  an  almost  diagnostic 
sign  of  this  affection  may  be  found  in  the  fact  that  the  stomach  is  quiet  so 
long  as  the  patient  keeps  the  head  upon  the  pillow,  but  the  distress  occurs 
at  once  upon  rising  up.  In  some  cases  this  condition  of  depression  even 
replaces  the  normal  second  stage,  so  that  opium,  instead  of  inducing 
quiet  sleep,  will  provoke  alarming  depression  and  vomiting,  either  with 
or  without  drowsiness.  Thus,  cases  have  been  reported  in  which  one- 
fourth  of  a  grain,  or  a  somewhat  greater  quantity,  of  morphine,  hypo- 
dermically  injected,  has  been  followed  at  once  by  syncope,  with  strug- 
gling for  breath,  and  apparently  imminent  or  even  present  death.*  A 
rarer  idiosyncrasy  exists  in  those  persons  who  are  rendered  by  opium 
very  delirious,  it  may  be  even  wildly  so.  In  certain  cases  of  opium- 
poisoning,  partial  or  complete  convulsions  have  occurred  amidst  the  more 
usual  phenomena,  f  Severe  itching  of  the  skin  is  a  common  phenomenon 
when  the  action  of  opium  is  going  off,  and  there  are  persons  in  whom 
such  violent  erythema  is  produced  even  by  therapeutic  doses  as  to  forbid 

*  See  Report  of  the  Committee  on  the  Hypodermic  Method  of  Injection,  Medico-Chi- 
rurgical  Transactions,  i. ;  see  also  Medical  Times  and  Gazette,  1868,  cases  reported  by 
Braine  and  by  Roberts. 

t  Cases,  Brit.  Med.  Journ.,  1876,  ii.  496 ;  Pacific  Med.  and  Surg.  Journ.,  July,  1876. 


128  GENERAL   REMEDIES. 

the  use  of  the  drug  (case,  Wien.  Med.  Presse,  xxiv.  568)  ;  R.  V.  Jaksch14 
reports  temporary  blindness  as  produced  by  opium.  Glycosuria  has  been 
noticed  both  in  animals  and  man  ( Adler  ; l5  also  Luzzatto  l7). 

Opium  appears  to  act  so  differently  upon  the  lower  animals  than  upon 
man  that  it  seems  necessary  to  discuss  the  former  action  by  itself. 

As  long  ago  as  1826  Charvet 16  stated  that  opium  in  the  invertebrata  causes  pro- 
gressive loss  of  power  in  the  contractile  tissue,  ending  in  death  ;  in  fishes,  paralysis 
and  convulsions  ;  in  birds  and  mammals,  paralysis,  convulsions,  and  stupor. 

In  the  frog,  opium  and  morphine  act  similarly,  producing  primarily  a  condition 
of  violent  tetanus,  with  great  increase  of  the  reflex  activity,  ending,  if  the  dose  have 
been  large  enough,  in  a  progressive  paralysis  with  disturbed  respiration,  and  finally 
cessation  of  the  same.  W.  Baxt18  states  that  when  a  very  minute  dose  is  used  (15.25 
milligrammes)  after  a  period  of  heightened  excitability  there  is  stupor  with  in- 
creased reflex  excitability  as  it  passes  off.  As  was  first  shown  by  Kolliker,  and 
abundantly  demonstrated  since,  the  tetanus  is  not  prevented  by  section  of  the 
spinal  cord,  and,  with  the  heightened  reflex  activity,  is  therefore  due  to  spinal 
excitement.  It  is  probable,  however,  as  affirmed  by  Kolliker,19  by  Albers,2"  and  by 
Meihuizen,21  that  some  of  the  convulsions  are  epileptiform.  Albers  states  also  that 
convulsive  movements  occur  in  limbs  after  section  of  their  nerves,  a  fact  which 
seems  to  us  very  doubtful. 

S.  Weir  Mitchell72  has  shown  that  birds,  as  represented  by  pigeons,  chickens, 
and  ducks,  are  very  insusceptible  to  the  toxic  action  of  opium  and  its  chief  deriva- 
tive, morphine.  It  appears  to  be  impossible  to  kill  a  pigeon  by  opium  given  by  the 
mouth,  and  of  morphine  from  eight  to  fifteen  grains  are  required  to  produce  a  fatal 
result ;  but  when  given  hypodermically  from  two  to  three  grains  of  the  alkaloid 
suffice.  The  symptoms  induced  have  been  very  uniform  :  they  are  unsteadiness, 
labored  breathing,  increasing  signs  of  dyspnoea,  unaltered  pupils,  and,  finally,  gen- 
eral convulsions  and  death.  No  true  hypnotic  effect  has  been  observed,  but  a  curi- 
ous and  very  great  rise  of  temperature  just  before  death  was  noted  in  one  case.  As 
Flourens  affirms  that  a  single  grain  of  the  aqueous  extract  of  opium  will  throw  a 
sparrow  into  a  profound  stupor,  it  can  scarcely  be  considered  as  proved  that  the 
drug  acts  upon  all  birds  as  upon  those  experimented  with  by  Mitchell. 

According  to  M.  L.  Gurnard,2"  in  the  cat  morphine  produces  violent  hyper- 
excitability',  great  restlessness,  agitation,  hallucinations,  dilated  pupils,  accelerated 
heart  and  respiration,  from  which  the  animal  returns  to  its  normal  condition  unless 
the  dose  have  been  very  large,  when  tetanic  convulsions  develop. 

Upon  dogs*  morphine  acts  very  much  as  upon  man.t  In  very  many  cases,  if 
not  in  the  majority,  eight  to  ten  grains  of  the  alkaloid  injected  into  a  dog  of  mod- 
erate size  will  cause  deep  sleep,  amounting  to  coma,  so  that  the  animal  will  remain 
in  any  position  in  which  he  may  be  placed.  The  length  and  depth  of  this  sleep 
are,  of  course,  proportionate  to  the  dose  :  when  at  all  profound,  it  is  accompanied 
by  marked  insensibility  to  pinching  and  other  forms  of  external  irritation.  A  repe- 
tition of  irritation,  and  especially  a  sudden  loud  noise  or  shaking,  will,  however, 
arouse  the  animal,  precisely  as  in  man.  Indeed,  sometimes  the  dog,  even  when 
comatose,  seems  more  than  normally  sensitive  to  sudden  noise,  trembling  and 
starting  in  an  almost  convulsive  manner.  After  awaking,  the  dog  shows  unmis- 


*  According  to  JofTroy  and  Serveaux  (Archiv  d.  Med.  Exfter.  Anal.  Path.,  1898,  x.), 
the  fatal  dose  of  morphine  is  :  for  dogs,  intravenously  0.029  gramme  per  kilo,  hypodermi- 
cally 0.035  per  kilo ;  for  rabbits,  intravenously  0.15  per  kilo,  hypodermically  0.25  per  kilo. 

t  Harley,  The  Old  Vegetable  Neurotics,  107,  London,  1869 ;  Claude  Bernard,  Ar- 
chives Generates,  ii.  437,  6th  series,  1864  ;  J.  I.  Reese.  American  Journal  of  the  Medical 
Sciences,  Jan.  1871. 


SOMNIFACIENTS.  129 

takable  signs  of  nervous  and  psychical  depression.  In  walking,  the  hind  legs  are 
dragged,  as  though  semi-paralyzed  ;  the  eyes  are  haggard ;  the  naturally  brave 
animal  cowers  in  a  corner  or  seeks  to  hide  himself,  no  longer  recognizing  his  mas- 
ter, and  does  not  return  to  his  natural  condition  for  many  hours.  After  smaller 
doses  the  effects  are  proportionately  less  intense.  It  has  been  shown  by  Harley  that 
in  some  dogs,  precisely  as  in  some  people,  morphine  fails  to  exert  its  usual  hypnotic 
action,  but  produces  great  depression,  as  evinced  by  faintness,  prolonged  nausea, 
and  retching,  interrupted  only  by  intervals  of  dreamy  delirious  somnolency. 

In  the  horse  (Harley)  two  or  even  three  grains  of  morphine  hypodermically 
injected  produce  sometimes  a  slight  drowsiness,  sometimes  no  perceptible  effect. 
Doses  of  from  four  to  six  grains  cause  great  restlessness  and  accelerated  pulse. 
The  mouth  is  moist,  the  temperature  of  the  skin  and  its  secretion  increased  ;  the 
animal  paws  continually,  and  treads  about  in  his  stall  with  an  almost  rhythmical 
movement.  After  twelve  grains,  Harley  noticed  in  some  cases  very  great  excite- 
ment, as  shown  by  marked  increase  in  the  rapidity  of  the  heart's  action,  by  mus- 
cular rigidity  and  tremors,  and  by  the  animal's  walking  rapidly  to  and  fro,  slobber- 
ing and  sweating  profusely.  In  another  horse,  after  an  immediate  strong  erection 
of  the  penis  and  copious  emission  of  semen,  heavy  sleep  came  on,  interrupted  after 
the  third  hour  by  the  usual  symptoms  of  excitement.  Thirty-six  grains  of  mor- 
phine acetate  caused  in  a  powerful  hunter  deep  comatose  sleep,  commencing  in 
fifteen  minutes  and  lasting  for  three  hours,  when  it  was  replaced  by  intense  restless- 
ness and  severe  delirium,  continuing  for  seven  hours.  During  this  time  the  animal 
was  perfectly  blind.  Previously  to  these  studies,  Barbier  had  found  that  four 
drachms  of  the  aqueous  extract  of  opium  produced  violent  tremblings,  apparent 
insensibility  to  external  irritants,  convulsions  without  coma,  and  death.  One  hun- 
dred grains  of  morphine  acetate  killed  a  horse  by  convulsions  in  three  hours.  Ernst 
.  Hess M  has  shown  that  in  the  ruminants  morphine  produces  first  excitement  and 
then  narcosis. 

In  the  mouse,  according  to  the  experiments  of  Harley,  the  first  effect  of  an 
injection  of  from  one-twentieth  to  one-twelfth  of  a  grain  of  morphine  is  a  tonic 
cramp-like  contraction  of  the  muscles,  especially  of  the  trunk,  of  such  character 
that  periods  of  forced  rest  alternate  with  a  slow,  laborious  creep,  which  seems  to 
originate  not  in  the  limbs  but  in  the  trunk  itself.  There  is  in  this  state  no  tendency 
to  somnolency,  but,  on  the  contrary,  an  abnormal  sensitiveness  to  loud  sounds, 
which  cause  the  mouse  to  resume  for  a  moment  active  running  movements.  The 
breathing  is  irregular,  the  pulse  accelerated,  and  finally  stupor  develops  itself,  and 
coma  deepens  into  death  by  dyspnoea  ;  or,  otherwise,  recovery,  preceded  by  con- 
vulsive movements  of  the  hinder  part  of  the  body,  is  gradually  brought  about. 

In  reviewing  the  action  of  morphine  upon  the  lower  animals,  it 
becomes  very  evident  that  two  classes  of  phenomena  are  everywhere  dis- 
cernible,— i.e. ,  the  spinal  and  the  cerebral, — and  that  the  higher  in  the 
scale  of  life  any  given  animal  may  be  the  more  marked  are  the  brain- 
symptoms.  These  cerebral  phenomena  are  mostly  sleep  and  stupor  ; 
but,  as  is  well  known,  in  some  human  individuals  morphine  acts  as  a 
delirifacient ;  and  it  seems  very  probable  that  the  peculiar  restlessness 
of  the  horse  under  the  influence  of  the  alkaloid  is  due  to  delirium,  and 
not  to  spinal  excitement. 

When  looked  at  in  this  manner,  it  seems  to  us  that  morphine  does 
not  act  so  differently  as  has  been  generally  asserted  upon  the  lower  ani- 
mals and  upon  man.  The  immensely  higher  cerebral  organization  of  the 
latter,  with  the  immensely  greater  sensitiveness  which  it  involves,  makes 
the  man  correspondingly  more  susceptible  to  the  cerebral  action  of  the 


130  GENERAL   REMEDIES. 

drug  :  hence  not  only  is  he  affected  by  much  smaller  doses  of  the  alka- 
loid than  are  the  lower  animals,  but  as  the  spinal  symptoms  are  trium- 
phant in  the  frog  because  its  spinal  system  is  vastly  more  developed  than 
its  cerebral,  so  in  man  the  cerebral  symptoms  mask  the  spinal  because  in 
him  the  brain  is  more  developed  than  the  cord.  The  two  creatures — man 
and  the  frog — occupy  the  two  extremes  of  the  series  ;  between  them  is 
probably  to  be  found  every  gradation.* 

The  action  of  opium  upon  dogs  and  rabbits  is  sufficiently  close  to  that 
upon  man  to  enable  us  to  reason  from  experiments  upon  the  former  as  to 
the  influence  of  the  alkaloid  upon  the  circulation  and  respiration  in  the 
latter.  Indeed,  so  far  as  these  functions  are  concerned,  morphine  appears 
to  act  identically  in  both  instances. 

Action  on  the  Nervous  System. — The  cerebral  symptoms  produced  by 
opium  are  without  doubt  due  to  a  direct  influence  of  the  drug  upon  those 
cells  which  preside  over  intellectual  action  and  consciousness.  Opium  is 
frequently  spoken  of  as  a  cerebral  stimulant,  and  some  of  the  world' s  most 
famous  writings  have  undoubtedly  been  produced  under  its  influence.  It 
appears,  however,  to  be  especially  related  with  those  tissues  that  are 
connected  with  imagination,  so  that  it  is  the  imagination  rather  than  the 
reasoning  functions  which  is  affected  by  it.  In  this  respect  it  is  not  so 
true  an  intellectual  stimulant  as  is  caffeine.  It  is  undoubtedly  a  stimu- 
lant to  the  spinal  cord  ;  but,  as  has  already  been  shown,  the  cerebrum  in 
man  is  so  infinitely  more  susceptible  to  its  influence  than  is  the  spinal 
cord  that  this  spinal  effect  is  rarely  perceptible  in  man,  even  in  toxic 
dose. 

Nerves. — According  to  Gscheidlen,28  morphine  primarily  increases  and 
secondarily  depresses  the  excitability  of  the  motor  nerves  of  the  frog,  the 
period  of  heightened  functional  activity  not  being  demonstrable  after  enor- 
mous doses.  Albers20  affirms  that  depression  may  develop  into  com- 
plete paralysis  of  function,  though  Gscheidlen  has  never  been  able  to  verify 
this.  Gscheidlen  further  asserts  that  the  local  application  of  morphine 
intensifies  and  protracts  the  excitability  of  an  afferent  nerve  in  strychnine- 
poisoning.  No  phenomenon  of  human  poisoning  by  opium  can  be  attrib- 
uted to  its  action  on  nerve-trunks,  but  the  relief  of  pain  sometimes  obtained 
by  the  local  use  of  opium  would  indicate  that  in  concentrated  form  it 
depresses  the  sensory  fibres  even  of  human  nerves. 

Action  on  the  Circulation. — In  man  the  circulatory  phenomena  are  a 
slight  primary  evanescent  acceleration  of  the  pulse-rate  (see  Nothnagel  -5), 
succeeded  by  the  characteristic  slowing  and  increased  fulness  and  force 
of  the  pulse,  which  is  followed  by  a  return  to  the  normal  pulse,  or  a 
great  increase  of  rapidity  and  loss  of  strength,  during  the  third  stage. 
Gscheidlen  has  found  in  rabbits  and  dogs  after  the  injection  of  morphine, 
first  an  increase  in  the  pulse-rate,  then  a  decrease,  and  finally  return  to 

*  A  curious  corroboration  of  the  views  expressed  in  this  paragraph  is  found  in  the  fol- 
lowing sentence  taken  from  Althaus  (Diseases  of  the  Nervous  System,  New  York,  1878, 
135) :  "  In  infants,  however,  and  also  in  the  lower  races  of  mankind,  as  in  negroes  and 
Malays,  convulsions  are  observed  after  its  [opium]  ingestion." 


SOMNIFACIENTS.  131 

the  normal  pulse,  or  else  increased  rapidity.  Sphygmographic  studies 
of  the  effects  of  small  doses  of  morphine  have  been  made  with  various 
results  by  several  observers  :  undoubtedly  in  some  individuals  therapeutic 
amounts  of  the  alkaloid  depress  sensibly  the  circulation,  but,  in  agreement 
with  Riegel  and  Preisendorffer,26  it  can  scarcely  be  doubted  that  therapeu- 
tic doses  have  no  sensible  effect  upon  the  circulation  in  the  ordinary  man. 
It  has  been  found  by  M.  L.  Guinard27  that  in  the  dog  morphine  produces 
primarily  a  slight  rise  of  the  arterial  pressure,  followed  by  a  fall  during 
the  period  of  narcosis. 

The  slow,  full  pulse  of  the  second  stage  of  opium -poisoning  is  due  to 
an  action  of  the  drug  upon  the  inhibitory  cardiac  nerves,  as  may  also 
possibly  be  in  some  manner  the  increased  arterial  pressure  ;  for  Gscheid- 
len  has  experimentally  demonstrated  that  after  section  of  the  vagi  mor- 
phine is  powerless  to  lower  the  pulse,  and  also  that  division  of  the  nerves 
during  the  second  stage  of  morphine-poisoning  is  followed  by  an  extra- 
ordinary rise  in  the  pulse-rate.  That  the  peripheral  ends  of  the  vagi  are 
stimulated  was  proved  by  the  fact  that  cardiac  arrest  took  place  when  the 
distal  ends  of  the  cut  nerve  were  more  feebly  irritated  than  would  suffice 
to  affect  the  unpoisoned  animal ;  and  that  the  inhibitory  cerebral  centres 
are  stimulated  was  demonstrated  by  the  instantaneous  very  great  fall  of 
the  pulse-rate,  amounting  in  some  cases  to  one- half  in  less  than  half  a 
minute,  which  ensued  upon  the  injection  of  a  large  dose  of  the  alkaloid 
into  the  carotid, — i.e. ,  into  the  brain  and  the  inhibitory  centres.  The 
rapid  feeble  pulse  of  the  third  stage  of  opium-poisoning  Gscheidlen  found 
to  be  due,  at  least  in  a  measure,  to  paralysis  of  the  peripheral  vagi ;  for 
at  such  time  stimulation  of  the  peripheral  end  of  the  cut  nerve  was 
powerless  to  affect  the  heart. 

The  experiments  of  Gscheidlen  also  indicate  that  morphine  exerts 
first  a  slight  stimulating,  then  a  depressing  influence  upon  the  heart-muscle 
or  ganglia,  since,  after  isolation  of  the  viscus  by  section  of  the  cord,  sym- 
pathetic, and  pneumogastric,  life  being  sustained  by  artificial  respiration, 
a  large  dose  of  morphine  induced  a  momentary  increase  in  the  number 
of  the  cardiac  contractions,  followed  by  a  marked  decrease  and  finally 
extinguishment  of  the  same.  This  conclusion  is  confirmed  by  Ringer 
and  Sainsbury,25*  who  found  that  opium  first  increased  the  power  of  the  cut- 
out heart  of  the  frog,  then  depressed  it,  and  finally  caused  diastolic  arrest. 

The  question  of  the  action  of  morphine  upon  the  vaso-motor  system 
is  of  great  interest,  but  cannot  at  present  be  fully  answered.  Gscheidlen 
believes  that  it  first  stimulates  and  then  depresses  it,  and  asserts  that 
after  the  injection  of  a  large  dose  the  arterioles  in  the  mesentery  can 
be  seen  to  contract,  and  later  (third  stage)  to  dilate.  The  objections  to 
this  sort  of  evidence  are  sufficiently  stated  elsewhere  in  this  book  ;  and 
the  rise  of  the  arterial  pressure,  which  he  also  adduces  as  an  argument, 
may  be  accounted  for  without  calling  upon  the  aid  of  the  vaso-motor 
nerves.  While,  therefore,  it  is  probable  that  morphine  does  exert  the 
influence  he  asserts  for  it,  the  question  must  still  be  considered  as  sub 


I32  GENERAL   REMEDIES. 

judicc :  that  the  vaso-motor  system  is  not  paralyzed  even  in  extremis 
is  shown  by  Gscheidlen's  experiment,  in  which  electrical  stimulation  of 
the  cord  at  such  time  induced  immediate  rise  of  the  arterial  pressure. 
The  action  of  morphine  upon  the  brain  is  certainly  independent  of  any 
action  on  the  vessels.* 

Action  on  the  Respiration. — Death  occurs  from  opium,  in  the  great 
majority  of  cases,  by  failure  of  the  respiration  ;  and  that  such  failure  is 
due  to  a  direct  action  of  the  poison  upon  the  respiratory  centres  in  the 
medulla  is  proved  by  the  fact  that  morphine  affects  the  breathing  of  dogs 
and  rabbits  whose  pneumogastrics  have  been  cut  as  much  as  it  does  those 
whose  nerves  are  entire  (Gscheidlen). 

The  action  of  opium  or  morphine  upon  the  elimination  of  carbonic 
acid  has  been  studied  by  Boeck  and  Bauer  *°  and  by  Chittenden  and  Cum- 
mins.*1 Their  results  are  concordant  in  showing  that  the  effect  of  the 
alkaloid  upon  carbonic  acid  production  is  in  direct  relation  to  its  influence 
upon  the  muscular  system.  The  elimination  is  increased  when  convul- 
sions occur,  but  decreased  when  narcotic  quietude  is  produced.  Accord- 
ing to  Reichert,12  the  fall  of  temperature  produced  by  the  toxic  dose  of 
morphine  is  caused  by  a  lessening  of  heat  production,  which  is  due  to 
depression  of  thermogenic  centres  in  the  caudate  nucleus.  Luzzatto60 
found  that  under  the  influence  of  morphine  there  is  a  very  marked  increase 
in  the  destruction  of  nitrogenous  tissue. 

Action  on  the  Pupil. — Since  morphine  locally  applied  does  not  affect 
the  pupil,  it  follows  that  its  contracting  action  upon  the  latter  is  through 
the  nerve-centres.  It  is  probable,  but  has  not,  that  we  are  aware  of,  been 
experimentally  proved,  that  the  contraction  of  the  pupil  is,  at  least,  largely 
due  to  stimulation  of  the  oculo-motor  nerve-centres,  and  that  the-dilatation 
of  the  pupil  as  death  approaches  is  due  to  a  paralysis  of  the  same.  Indeed, 
it  cannot  well  be  otherwise  ;  for  if  the  primary  contraction  were  due  to 
paralysis  of  the  sympathetic,  the  secondary  wide  dilatation  would  be  im- 
possible ;  the  dilating  force — i.e. ,  the  sympathetic — having  been  with- 
drawn, the  pupil  would  not  widely  expand  even  if  the  contracting  force 
— i.e. ,  the  oculo-motor — were  paralyzed. 

In  birds  (S.  Weir  Mitchell)  the  pupil  is  not  affected,  probably  for  anatomical 
reasons  (see  Atropine}.  In  horses  it  is  widely  dilated  (Harley)  ;  and  in  dogs  it 
dilates  before  contracting  (Reese,  apparently  confirmed  by  Experiment  No.  8,  Har- 
ley), or  sometimes  remains  unchanged  (Harley).  At  present  these  anomalies  can- 
not be  explained. 

Secretions. — Opium  ordinarily  checks  all  the  secretions  of  the  body, 
although  this  influence  is  capable  of  being  modified  by  certain  drugs  so  as 
to  produce  a  sudorific  action.  By  it  the  urinary  secretion  is  habitually 
diminished,  owing,  as  has  been  shown  by  Thompson,33  to  a  direct  action 
upon  the  kidneys.  Retention,  which  after  a  full  dose  of  opium  is  not  rare, 
depends  upon  the  blunting  of  the  sensibility  of  the  bladder. 

*  Consult  Binz,  Arch.  f.  Exper.  Pathol.  und  Pharm.,  vi.  310;  Vulpian,  Lcqons  sur 
VAppar.  vaso-moteur,  ii.  156. 


SOMNIFACIENTS.  133 

Intestines. — Opium,  and  to  a  less  extent  morphine,*  has  a  very  pro- 
nounced influence  upon  the  digestive  tract,  in  many  persons  producing 
nausea,  in  all  lessening  the  appetite  and  the  activity  of  digestion  and 
causing  constipation.  The  disorder  of  digestion  and  the  constipation  are 
in  part,  at  least,  due  to  an  arrest  of  secretion,  probably  both  in  the  stom- 
ach and  in  the  intestines  ;  but  they  are  also  probably  to  some  extent 
due  to  the  checking  of  peristalsis,  an  effect  which  can  often  be  shown 
in  men,  and  which  Nothnagel34  and  Ott35  have  demonstrated  upon 
animals,  f  Both  Nothnagel  and  Ott  affirm  that  the  toxic  dose  of  morphine 
in  the  lower  animals  increases  peristaltic  movement,  which  affords  a  pos- 
sible explanation  of  the  diarrhoea  sometimes  seen  in  chronic  opium-eaters. 
The  checking  of  peristalsis  appears  to  be  due  to  stimulation  of  the 
inhibitory  nerve  apparatus  ;  the  increase  to  paralysis  of  the  same. 

SUMMARY.— Opium  is  a  cerebral  stimulant,  whose  action  soon 
passes  into  sedation  and  the  production  of  sleep,  and  has  the  power  of 
relieving  pain  in  some  -way  as  yet  not  thoroughly  known  ;  probably, 
however,  by  benumbing  the  perceptive  centres  in  the  brain.  It  acts 
upon  the  spinal  cord  of  many  of  the  lower  animals  as  a  stimulant,  but 
in  man  its  influence  is  not  perceptible.  It  both  slows  the  pulse  and  in- 
creases to  some  extent  the  force  of  the  circulation  by  an  action  upon 
the  inhibitory  nerve-centres,  probably  both  centric  and  peripheral,  and 
by  a  slight  stimulant  influence  upon  the  heart-muscle  or  its  intrinsic 
ganglia.  It  is  a  centric  respiratory  depressant ;  it  contracts  the  pupil 
by  a  centric  action  which  is  probably  that  of  stimulation  of  the  oculo- 
motor nerve-centres. 

THERAPEUTICS. — The  chief  indications  for  the  use  of  opium  are  con- 
sidered below,  seriatim.  Nearly  all  of  them  flow  evidently  from  the 
known  physiological  action  of  the  drug ;  others,  however,  although 
established  by  clinical  experience,  and  undeniable,  are  not  so  plain  in 
their  philosophy. 

1.  To  relieve  pain.     As  an  analgesic,  opium  is  without  a  rival  in  the 
materia  medica,  except  it  be  the  anaesthetics.      It  is  used  to  allay  pain 
arising  from  any  cause  whatever,  except  acute  inflammation  of  the  brain, 
and  is  preferred  to  the  anaesthetics  whenever  the  pain  has  any  permanency. 
In  painful  spasm  it  is  especially  useful,  as  it  seems  very  frequently  to 
quiet  the  motor  as  well  as  the  sensory  disturbance. 

2.  To  produce  sleep.   Sleeplessness  occurring  in  acute  disease,  and 
not  dependent  upon  cerebral  inflammation,  may  very  frequently  be  re- 
lieved by  opium.     While  it  is  often  necessary  to  use  the  drug  freely  in 
such  affections  as  delirium  tremens,  care  should  be  exercised  not  to  over- 
whelm the  nerve-centres  by  enormous  doses.      In  habitual  sleeplessness 

*  Vamossy  (Deutsche  Med.  Wochensch.,  1897,  xxiii.)  has  endeavored  to  determine 
experimentally  why  opium  causes  constipation  more  than  does  morphine.  He  finds, 
however,  that  neither  narcotine,  thebaine,  codeine,  kryptopine,  nor  laudanine  is  equal  in 
power  of  checking  peristalsis  to  morphine  ;  and  that  it  is  not  probable  that  any  of  them 
are  responsible  for  the  constipating  effects  of  the  crude  drug. 

t  The  theory  of  Hirsch,  that  morphine  causes  contraction  of  the  pylorus,  is  very  im- 
probable, since,  granting  the  correctness  of  his  experimental  results,  a  more  probable 
explanation  is  that  gastric  peristalsis  is  checked  by  the  alkaloid. 


134  GENERAL   REMEDIES. 

great  caution  must  be  used  in  the  employment  of  opium,  not  so  much 
on  account  of  the  disturbance  of  digestion  which  it  is  liable  to  cause,  as 
for  fear  of  producing  the  ' '  opium  habit. ' '  Chloral  is  perhaps  a  more 
generally  applicable  hypnotic  than  opium.  Be  this,  however,  as  it  may, 
we  have  found  the  combination  of  morphine  and  chloral  singularly  effi- 
cient. In  low  fevers,  adynamic  delirium  often  coexists  with  sleeplessness, 
and  is  then  best  met  by  opium. 

3.  To  allay  irritation.     In  various  forms  of  nervous  erethism,  opium 
is  most  valuable  ;  but  when  the  affection  is  at  all  chronic,  the  dangers 
of  the  opium  habit  should  not  be  lost  sight  of.     On  the  other  hand,  in 
acute  cases,  as  in  the  excitement  which  so  frequently  attends  hemoptysis, 
the  drug  should  be  used  freely.      In  many  cases  of  disease,  opium  is 
serviceable  by  sustaining  the  system  against  an  irritation  for  the  time 
being  irremediable,  by  blunting  the  sensibilities.      In  this  way  it  is  useful 
in  the  advanced  stages  of  small-pox,  and  in  various  surgical  affections,  in 
which  it  also  does  good  by  allaying  pain.      In  various  local  irritations 
opium  is  continually  employed,  as  in   colic  caused  by  undigested  food, 
and  in  bronchitis  to  quiet  cough. 

By  allaying  irritation  and  pain,  opium  affords  relief  in  most  cases  of 
inflammation  ;  but  in  certain  varieties  of  the  affection  it  seems  to  do  much 
more  than  this,  exerting,  in  some  way  at  present  difficult  to  explain,  a 
life-saving  influence.  In  peritonitis,  after  due  depletion,  or  in  cases  not 
requiring  depletion,  it  should  always  be  exhibited  in  large  doses  at  regu- 
lar intervals,  in  such  a  way  as  to  keep  the  patient  in  a  state  of  decided 
narcotism. 

In  severe  acute  vomiting,  opium  is  one  of  the  most  reliable  remedies. 
It  is  best  used  in  the  form  of  suppositories.  Although,  by  checking 
secretion  and  peristalsis,  opium  usually  causes  constipation,  yet  when 
obstruction  of  the  bowels  is  produced  by  spasm  due  to  an  irritation  or 
inflammation,  by  relieving  the  latter  the  drug  will  sometimes  act  as  a 
most  efficient  laxative. 

4.  To  check  excessive  secretion.    For  this  purpose  opium  is  very  largely 
employed  in  diarrhoeas,  and  is  very  efficient  either  alone  or  in  combi- 
nation with  various  remedies.      In  enteritis  and  in  dysentery,  although  no 
less  frequently  used  than  in  diarrhoea,  it  is  of  service  as  an  antiphlogistic 
and  analgesic  rather  than  by  checking  secretion.     In  diabetes  insipidus, 
the  combination  of  it  and  gallic  acid  has  been  much  used,  and  is  often 
effective. 

In  true  saccharine  diabetes,  opium  is  of  very  great  value  in  many 
cases,  often  ameliorating  the  symptoms,  and,  in  conjunction  with  re- 
stricted diet,  sometimes  even  effecting  a  cure.  Of  course,  however,  like 
all  other  known  remedies  in  this  disease,  it  most  frequently  acts  simply 
as  a  palliative.  It  must  be  given  in  large  ascending  doses, — the  patient  for 
the  time  being  indeed  made  an  opium-eater, — a  procedure  justified  only 
by  the  fatal  nature  of  the  malady. 

5.  To  support  the  system.     Opium  appears  in  low  fevers,  and  in  vari- 


SOMNIFACIENTS.  135 

ous  protracted  adynamic  illnesses,  to  afford  actual  support  to  the  system 
in  some  way  not  as  yet  made  out.  This  is  especially  the  case  when, 
from  any  reason,  sufficient  food  to  keep  up  life  cannot  be  taken  or 
retained.  Opium  is  a  valuable  remedy  for  the  purpose  of  protracting 
and  rendering  more  comfortable  life  in  the  aged.  When  the  bodily 
powers  are  failing,  and  various  functional  disorders  are  from  time  to 
time  occurring,  it  is  often  possible  to  check,  by  the  use  of  opium,  attacks 
which,  if  allowed  to  obtain  headway,  would  extinguish  the  flickering 
life.  Further,  in  many  cases  of  feeble  very  old  and  suffering  people  the 
habitual  use  of  opium  under  careful  restriction  of  the  physician  is  not  only 
justifiable,  but  necessary  if  life  is  to  be  maintained  as  long  as  possible. 
In  such  persons  the  danger  of  forming  an  opium  habit  which  shall  do 
injury  is  reduced  to  a  minimum. 

6.  As  a  sudorific.  In  1873  A.  Loomis36  stated  that  in  acute  urtzmia 
large  hypodermic  injections  of  morphine  would  control  the  convulsions, 
at  the  same  time  producing  a  profuse  diuresis,  which  has  been  confirmed 
by  Fiset."  The  method  of  treatment  has  been  largely  followed,  in  some 
instances  with  very  happy  effect,  but  in  other  cases  has  apparently  pro- 
duced death.  Whenever  the  kidneys  are  seriously  diseased  the  free 
administration  of  opiates  is  attended  by  much  danger,  because  the  chief 
channel  through  which  the  opium  alkaloids  escape  from  the  system  is 
choked  up.  As  a  general  sudorific  opium  is  used  almost  exclusively  in 
the  form  of  Dover's  powder.  (See  Dover's  powder  in  Diaphoretics.) 

TOXICOLOGY. — The  positive  medico-legal  diagnosis  of  opium-poison- 
ing from  the  symptoms  alone  is  not  possible,  even  in  the  most  character- 
istic cases,  because  the  phenomena  produced  by  cerebral  congestion, 
apoplexy,  and  uraemia  may  be  identical  with  those  of  opium-poisoning. 
Inequality  of  the  pupils,  which  has  been  considered  proof  that  a  case  is 
not  narcotism,  has  been  reported  by  Taylor88  as  present  in  poisoning.  In 
atypical  cases  without  a  history,  even  the  working  diagnosis  may  be  very 
difficult.  The  spinal  symptoms  may  entirely  overshadow  the  cerebral 
phenomena  ;  trismus,  tetanic  convulsions,  tonic  rigidity  of  the  muscles, 
spastic  gait,  marked  heightened  reflexes,  and  ankle  clonus  have  been 
reported  as  produced  by  the  drug  in  the  adult.*  In  children  it  is  com- 
mon for  the  nerve-centres  to  be  at  once  overpowered  by  the  poison,  so 
that  the  second  stage  may  be  very  much  shortened  or  entirely  aborted, 
and  collapse  with  unconsciousness  develop  almost  at  once.f 

Treatment  of  Opium- Poison. — Tannic  acid  is  feebly  antidotal  to  mor- 
phine, but  it  has  been  entirely  displaced  by  potassium  permanganate, 
which  rapidly  destroys  the  alkaloid  by  oxidation.  The  allegation  that 
potassium  permanganate  is  capable  of  following  morphine  into  the  blood 
and  there  destroying  it  is,  a  priori,  improbable,  and  it  has  been  experi- 
mentally shown  that  the  hypodermic  injection  of  potassium  permanganate 

*  For  cases,  see  Philadelphia  Med.  Journ.,  1903,  xiii.  497,  539,  613. 
t  For  discussion  of  effect  on  nursling  and  foetus  when  morphine  is  given  to  the  mother, 
see  Amer.  Journ.  Obstet.,  1877. 


136  GENERAL   REMEDIES. 

in  morphine-poisoning  is  futile.  *  Nevertheless,  during  the  whole  nar- 
cosis, there  should  be  repeated  administrations  of  potassium  permanganate 
by  the  mouth  for  the  purpose  of  destroying  morphine  excreted  into  the 
stomach.  Besides  the  administration  of  the  antidote,  the  indications  in 
opium-poisoning  are  to  evacuate  the  stomach,  to  maintain  respiration,  and 
to  keep  up  the  circulation  when  failing.  The  first  of  these  indications 
may  be  met  in  two  different  ways  :  by  an  emetic,  and  by  the  stomach- 
pump  or  tube  used  as  a  siphon.  There  is  often  in  narcotic  poisoning 
great  difficulty  in  getting  an  emetic  to  act,  owing  to  the  obtunding  of  the 
sensibility  of  the  nervous  system  by  the  poison.  For  this  and  other  reasons, 
so  palpable  as  not  to  need  mentioning,  only  a  prompt  stimulant  emetic 
should  be  used.  Antimony,  on  account  of  its  depressing  influence,  should 
always  be  avoided.  Mustard  flour  is  almost  always  to  be  had  at  once, 
and  is  very  efficient.  A  heaped  tablespoonful  stirred  up  in  a  tumblerful 
of  warm  water  should  be  exhibited  as  soon  as  possible,  and,  if  it  fail  to 
act  in  fifteen  minutes,  should  be  repeated  ;  if  this  fail,  a  powder  of  thirty 
grains  each  of  zinc  sulphate  and  ipecacuanha  may  be  given,  to  be  repeated 
at  intervals  of  twenty  minutes.  Large  draughts  of  warm  water  should  be 
administered  in  the  intervals,  and  also  between  the  acts  of  vomiting,  so  as 
thoroughly  to  wash  out  the  stomach.  The  stomach-pump  f  is  of  no  value 
when  the  solid  drug  has  been  ingested,  but,  if  at  hand,  is  preferable  to 
emetics  when  a  fluid  preparation  has  been  taken,  because  of  the  prompt- 
ness and  thoroughness  of  its  results. 

To  maintain  respiration  is  the  ultimate  object  of  all  the  measures 
which  are  commonly  undertaken  for  the  purpose  of  arousing  the  system 
in  opium- poisoning.  Unconsciousness  in  itself  is  of  no  moment,  but  as 
it  deepens  the  sensibility  of  the  respiratory  centres  grows  less,  and  con- 
sequently the  involuntary  breathing  is  less  rapidly  or  less  perfectly  per- 
formed. More  than  this,  when  at  all  awake,  a  patient  suffering  from 
opium-poisoning  can  be  made  to  supplement  the  almost  suspended  auto- 
matic breathing  by  voluntary  respiration,  and  every  effort  to  induce  him 
to  do  this  should  be  used.  It  is  often  surprising  how  an  apparently  un- 
conscious man  can  be  made  to  breathe  by  a  command  shouted  in  his  ear. 

*  See  Leedom  Sharp  ( Therap.  Gaz.,  1895) ;  also  E.  Q.  Thornton  and  Charles  A. 
Holder  (Therap.  Gaz.,  1897). 

f  The  siphon  stomach-pump  may  be  readily  extemporized.  It  consists  simply  of  an 
india-rubber  tube  three  and  a  half  to  four  and  a  half  feet  in  length,  of  proper  calibre, 
which  is  passed  into  the  stomach.  The  external  end  being  elevated,  water  is  poured  into 
it  until  the  stomach  is  full ;  then,  without  the  tube  being  allowed  to  empty  itself,  the 
external  end  is  dropped,  when,  of  course,  the  flow  of  water  is  reversed. 

The  value  of  strychnine  as  a  respiratory  stimulant  in  various  forms  of  narcosis  was 
first  demonstrated  in  the  laboratory  by  H.  C.  Wood,  and  subsequently  cases  were 
reported  by  Clara  Dercum  ( U.  M.  M.,  1870)  and  others. 

In  regard  to  the  value  of  atropine,  E.  F.  Bashford  (A.  I.  P.,  1901,  viii.)  confirms  its 
usefulness  in  opium-poisoning  ;  whilst  in  a  very  elaborate  paper  E.  T.  Reichert  (T.  M., 
1901)  reaches  the  conclusion  that  very  frequently  the  overdosing  of  cases  of  morphine- 
poisoning  with  atropine  has  contributed  to  the  fatal  result,  and  that  it  is  only  of  use  as  a 
respiratory  and  stimulating  agent  before  the  third  stage  of  the  poisoning  is  reached  ;  and 
further,  that,  on  account  of  its  in  many  ways  synergizing  with  morphine,  it  is  dangerous 
when  given  in  overdose.  In  these  conclusions  Reichert  seems  to  us  correct. 


SOMNIFACIENTS.  137 

To  keep  a  patient  awake,  walking,  flagellations  with  small,  fine  twigs, 
shaking,  shouting,  and  various  other  methods  which  may  suggest  them- 
selves, should  be  practised.  Care  should  always  be  exercised  not  to 
carry  these  useful  measures  unnecessarily  far,  and  perhaps  add  physical 
exhaustion  to  the  natural  prostration  of  the  third  stage.  The  strong 
faradic  current  offers  a  means  of  causing  pain,  and  therefore  of  rousing 
the  patient,  without  leaving  bruises  or  other  after-effects. 

The  cold  douche  is  also  an  excellent  method  of  rousing  the  patient 
and  at  the  same  time  of  especially  stimulating  respiration.  The  simplest 
method  of  application  is  to  support  the  head  and  shoulders  of  a  patient 
stripped  to  the  waist  over  a  common  wash-tub,  and  to  dash  the  water  over 
the  chest  and  head.  The  effect  is  much  greater  if  ice-cold  water  and 
water  a  little  hotter  than  the  hand  will  bear  (115°  F. )  be  used  in  quick 
succession.  Very  strong  coffee  has  been  used  from  time  immemorial,  and 
may  be  substituted  by  the  alkaloid  caffeine.  The  alkaloids  which  are  to 
be  relied  upon,  however,  are  strychnine,  cocaine,  and  atropine,  and  of 
these  the  most  valuable  is  probably  strychnine,  next  cocaine.  The  alka- 
loids should  be  given  hypodermically,  in  moderate  doses  at  short  intervals, 
until  some  effect  is  manifested  upon  the  respiration.  The  pupil  is  not 
a  safe  guide  as  to  the  administration  of  atropine,  which  alkaloid  should, 
indeed,  never  be  given  in  very  large  doses.  In  all  cases  it  is  better  to  use 
two  or  more  of  these  alkaloids  than  larger  doses  of  a  single  one.  When  in 
advanced  stages  the  circulation  fails,  digitalis  and  strychnine  are  the  chief 
remedies,  but  alcohol  may  be  used  carefully,  the  danger  being  that  any 
excess  of  it  may  aid  in  depressing  the  heart.  In  severe  cases  it  is  wise  to 
give  digitalis  hypodermically  before  the  end  of  the  second  long  stage, 
so  as  to  get  its  stimulating  influence  upon  the  heart  in  the  coming  de- 
pression. 

As  the  result  of  numerous  experiments,  E.  T.  Reichert89  reaches  the 
conclusion  that  cocaine  is  almost  completely  antagonistic  to  morphine, 
combating  the  influence  of  the  morphine  not  only  upon  respiration  and 
circulation,  but  also  upon  the  general  metabolism,  and  synergizing  with 
the  morphine  only  in  its  action  upon  the  spinal  cord.  He  finds  that,  on 
the  whole,  it  acts  more  powerfully  upon  morphinized  than  upon  normal 
dogs.  For  cases  in  which  cocaine  was  used  in  opium-poisoning,  see  Amer. 
Med.  Journ. ,  1901. 

In  bad  cases  of  opium-poisoning  the  use  of  artificial  respiration  should 
not  be  postponed.  In  some  cases  the  Sylvester  method  may  suffice,  but, 
as  was  first  shown  by  Fell,40  forced  respiration  (see  page  115)  should  be 
resorted  to  whenever  respiration  fails.  Fell"  has  reported  recovery 
obtained  in  this  way  after  the  ingestion  of  thirty-three  grains  of  morphine. 
So  long  as  any  movement  of  the  heart  continues,  the  forced  respiration 
should  be  steadily  maintained.  Inhalations  of  oxygen  apparently  saved 
life  in  a  case  reported  by  Playfair.42  In  some  cases  the  lungs  become 
filled  with  bronchial  mucus  ;  under  such  circumstances  good  may  be 
achieved  by  placing  the  patient  in  an  inverted  position.  It  is  often 


i38  GENERAL   REMEDIES. 

essential  to  keep  up  the  temperature  of  the  body  by  artificial  means. 
Lauder  Brunton  and  Cash  have  found  that  the  fall  of  temperature  in  the 
poisoned  mammal  is  not  prevented  by  placing  the  animal  in  a  temperature 
a  little  below  that  of  the  body,  and  the  ordinary  methods  used  in  the  sick- 
room to  heat  the  cooling  human  body  are  of  very  little  service.  The 
hot  bath  or  a  water  bed,  two-thirds  filled  with  water  of  the  temperature 
of  150°  F.,  may  be  employed.  The  subcutaneous  or  intravenous  injec- 
tion of  normal  saline  solution  has  proven  of  value  in  desperate  cases  ;  the 
solution  probably  aids  in  the  elimination  of  the  poison  and  the  main- 
tenance of  the  circulation. 

Opium-poisoning  usually  has  no  sequelae,  but  amaurosis 43  and  glyco- 
suria 44  have  been  reported. 

In  regard  to  the  amount  of  opium  which  will  cause  death,  the  smallest 
fatal  dose  in  the  adult  on  record  is  one-sixth  of  a  grain  of  morphine.* 
According  to  A.  Calkins,45  four  grains  f  of  crude  opium  placed  in  the  ear 
have  caused  death  ;  also  four  grains  by  the  mouth  in  more  than  one  case. 
According  to  the  authority  just  quoted,  out  of  twenty-nine  reported  cases 
in  which  a  fluidounce  of  laudanum  was  taken,  nine  died.  The  maximum 
doses  from  which  recovery  has  occurred  without  emesis  are  fifty-five 
grains  of  the  solid  opium  and  six  ounces  of  laudanum.  The  death  of  an 
adult  female  has  been  attributed,  with  doubtful  accuracy,  to  thirty  grains 
of  Dover's  powder,  given  in  divided  doses.46  Recovery  is  asserted  after 
eighteen  grains  of  morphine  without  vomiting  (William  C.  Chaffee) ,  thirty 
grains  with  vomiting  (Playfair42),  and  even  thirty-three  grains  (Fell41). 

For  full  details  as  to  the  results  of  the  habitual  use  of  opium  or 
its  alkaloid,  the  reader  is  referred  to  the  treatise  of  Albrecht  Erlen- 
meyer  (Die  Morphiumsuchi} .  No  confidence  can  be  placed  in  the  state- 
ments of  the  opium-eater,  and  it  is  essential  for  cure  that  such  person 
be  in  a  hospital  or  be  confined  to  an  apartment  under  the  care  of  an 
absolutely  reliable  nurse,  so  that  the  orders  of  the  physician  can  be 
strictly  enforced.  The  basis  of  the  treatment  must  consist  in  the  with- 
drawal of  the  narcotic,  and  there  are  three  distinct  ways  in  which  this  can 
be  effected.  First,  the  opium  may  be  suddenly  taken  away  ;  secondly, 
it  may  be  taken  away  rapidly,  but  not  suddenly  ;  thirdly,  it  may  be  with- 
drawn very  gradually.  The  first  of  these  methods  is  undoubtedly  in  most 
cases  efficient,  but  is  often  attended  by  grave  danger  of  collapse,  and 
has  no  distinct  advantages  over  the  plan  of  rapid  withdrawal.  The  time 
required  for  the  very  gradual  withdrawal  of  the  remedy  is  too  great  for 
practical  purposes,  and  the  sufferings  of  the  patient  are  too  long  drawn 
out.  Unless  the  daily  dose  has  been  extraordinary  or  the  patient  is 
in  a  very  feeble  condition,  it  is  safe  to  withdraw  the  narcotic  entirely 

*  A  number  of  cases  are  now  on  record  in  which  death  has  been  produced  in  the  adult 
by  the  hypodermic  use  of  from  one-sixth  to  one-half  grain  of  morphine.  Consult  Oiicago 
Med.  Examiner,  May,  1878;  Quart.  Journ.  Psychology .  Med.,  1868,  ii.  739;  also  Bost. 
Med.  and  Surg.  Journ.,  1885,  i. 

f  Taken  from  the  Journal  de  Chimie,  1831.    Assuredly  there  is  a  mistake  in  this  case- 


SOMNIFACIENTS.  139 

in  from  seven  to  twelve  days.  A  convenient  plan  is  to  direct  that  a  solu- 
tion of  morphine  or  opium  be  prepared,  and  whenever  a  dose  is  taken 
out  an  equivalent  amount  of  water  be  added.  The  chief  symptoms  that 
follow  the  rapid  withdrawal  are  excessive  malaise,  insomnia,  complete 
loss  of  appetite,  vomiting,  diarrhoea,  and  great  feebleness.  We  have 
never  yet  seen  a  case  in  which  these  symptoms  were  so  uncontrollable  as 
really  to  cause  alarm  for  the  safety  of  the  patient.  Much  may  be  done 
by  proper  feeding.  The  food  should  consist  of  highly  nutritious,  stimu- 
lating, and  easily  digested  articles,  and  in  severe  cases  should  be  liquid, 
such  as  milk,  rich  soups,  etc.  When  the  circulation  fails,  alcohol  may  be 
used,  and  much  relief  may  be  afforded  by  massage,  and  often  by  simple 
rubbing  of  the  patient.  General  electrical  stimulation  and  faradization  of 
the  muscles  is  often  useful,  not  only  by  its  effect  upon  the  circulation,  but 
also  by  distracting  the  attention  of  the  patient  from  his  sufferings.  The 
use  of  the  alkaloid  cocaine  as  a  stimulant  has  been  recommended.  Good 
results  may  be  obtained  from  the  free  internal  administration  of  the  fluid 
extract  of  coca,  but  the  use  of  hypodermic  injections  of  cocaine  seems 
hardly  justifiable,  as  the  danger  of  setting  up  the  cocaine  habit  is  too 
great.  If  gastro- intestinal  irritation  exists,  bismuth  may  be  administered 
freely.  The  diarrhoea  is  usually  controllable  by  mild  vegetable  astringents, 
especially  if  combined  with  sulphuric  acid.  If  the  bodily  temperature  falls 
at  all,  it  must  be  maintained  by  external  warmth.  Potassium  bromide, 
ammonium  valerianate,  Hoffmann's  anodyne,  and  other  similar  feeble 
nerve-sedatives  may  be  employed  and  give  some  comfort.  Moral  sup- 
port and  stimulation  are  essential,  and  massage  or  other  device  which 
aids  in  passing  the  time  of  suffering  is  most  beneficial. 

Opium- Smoking. — The  various  nations  of  the  Orient  use  opium  as  an 
intoxicant  by  smoking  in  one  of  two  ways.  In  Turkey  and  neighboring 
countries  it  is  placed  upon  tobacco,  in  a  small  pipe.  In  the  East  it  is 
usually  made  into  a  thick,  almost  plastic,  liquid,  a  large  drop  or  ball  of  which 
is  held  over  the  flame  of  a  small  oil  lamp,  and  the  resulting  fumes  inhaled 
through  pipes  of  various  forms.  For  an  elaborate  study  of  the  chemistry 
of  the  opiums  used  in  various  countries,  see  Apotheker  Zeitung,  1903. 

Moissan  has  found  in  the  smoke  of  opium  morphine,  pyrrol,  pyridine 
and  various  homologues,  acetone,  and  various  hydropyridine  bases,  all 
of  which  are  physiologically  active.  This  analysis  has  been  confirmed  by 
Hartwich  and  Simon,  who  believe  that  the  activity  of  the  opium  smoke 
depends  not  so  much  upon  the  morphine  as  upon  the  other  products  of 
the  destructive  distillation. 

ADMINISTRATION. — When  it  is  desired  to  produce  very  decided  nar- 
cotism by  the  use  of  repeated  doses  of  opium,  the  drug  should  always  be 
given  in  liquid  preparation,  since  opium  pills  sometimes  become  very 
hard  and  undergo  solution  so  slowly  that  their  accumulation  in  the  ali- 
mentary canal  is  possible.  On  the  other  hand,  in  diarrhoeas,  or  in  sick- 
ness of  the  stomach,  old  opium  pills  are  thought  by  some  to  act  better 
than  do  more  soluble  forms  of  the  drug. 

Many  persons  cannot  take  opium  on  account  of  the  very  great  sec- 


140  GENERAL   REMEDIES. 

ondary  nausea  and  depression  which  it  produces.  It  has  been  supposed 
that  these  disagreeable  after-effects  are  due  to  the  narcotine  in  opium  ; 
but  this  can  hardly  be,  seeing  that  they  often  follow  the  use  of  the  pure 
alkaloid,  morphine.  The  deodorized  tincture  of  opium  agrees  with  some 
individuals  better  than  any  other  preparation  of  the  drug  ;  and,  as  first 
pointed  out  by  Da  Costa,  by  giving  a  drachm  of  potassium  bromide  with 
twenty-five  drops  of  it,  the  after-effects  of  the  narcotic  are  often  en- 
tirely avoided.  In  many  neuralgic  women  the  knowledge  of  this  fact 
is  an  inestimable  boon  ;  in  others  the  unpleasant  symptoms  are  not  averted 
by  the  bromide. 

Children  always  bear  opium  very  badly,  *  and  to  them  only  the  weaker 
liquid  preparations  should  be  given.  Dover's  powder  should  especially 
be  avoided.  It  is  probable  that  in  its  manufacture  on  the  large  scale  the 
ingredients  are  sometimes  not  thoroughly  mixed  :  at  least  we  have  seen 
cases  in  which  the  symptoms  caused  by  it  were  seemingly  so  out  of  pro- 
portion to  the  dose  as  to  suggest  that  more  than  the  official  amount  of 
opium  was  present. 

In  acute  vomiting  from  any  cause,  in  dysentery,  in  strangury  and 
other  irritations  of  the  urino-genital  organs,  great  advantage  is  often  to 
be  gained  from  the  use  of  opium  by  the  rectum.  Suppositories  made  out 
of  the  extract  (gr.  ss  to  i),  or  enemata  of  laudanum  (gtt.  xxx  to  xl), 
may  be  used  in  these  cases.  The  latter  should  be  made  by  adding  the 
narcotic  to  a  tablespoonful  of  starch-water. 

The  dose  of  opium  for  an  adult  is  from  one  to  two  grains  ;  for  a  child 
a  year  old,  one-twenty-fourth  of  a  grain.  The  U.  S.  Pharmacopoeia 
directs  that  opium  in  its  normal  moist  condition  should  contain  not  less 
than  nine  per  cent,  of  morphine,  and  that  dried  powdered  opium  (Orii 
PULVIS,  U.  S. ),  out  of  which  the  preparations  are  made,  should  contain 
from  twelve  to  twelve  and  a  half  per  cent,  of  the  alkaloid. 

The  solid  preparations  are — the  deodorized  opium  (  OPIUM  DEODO- 
RATUM,  U.  S. ),  containing  from  twelve  to  twelve  and  a  half  per  cent,  of 
morphine  made  by  depriving  powdered  opium  of  all  substances  soluble  in 
benzin,  dose,  one  to  two  grains  (0.06-0.12  Gm. )  ;  pills  of  opium  (PiL- 
UL^E  OPII,  U.  S.),  containing  one  grain  each  of  powdered  opium  (0.065 
Gm. )  ;  extract  (EXTRACTUM  OPII,  U.  S.),  containing  twenty  per  cent. 
of  morphine,  three-quarters  of  a  grain  (0.05  Gm. )  are  about  equal  to 
one  grain  (0.065  Gm.)  of  powdered  or  deodorized  opium,  and  on  ac- 
count of  its  being  the  most  fixed  in  its  strength  of  any  of  the  solid 
preparations  of  opium,  as  well  as  of  its  being  free  from  the  noxious  con- 
stituents of  opium,  and  of  its  solubility  favoring  prompt  absorption,  it  is 
the  most  useful  and  reliable  of  all  the  solid  preparations  of  the  drug  ; 
Dover's  powder  ( PULVIS  IPECACUANHA  ET  OPII,  U.S.),  one  part  of 
opium,  one  part  of  ipecacuanha,  eight  parts  of  sugar  of  milk. 

*  In  a  babe  a  day  old,  one  minim  of  laudanum  (E.  Smith,  Lancet,  1854),  and  in  one 
aged  nine  months,  a  few  drops  of  paregoric  (Wood,  Host.  Med.  and  Surg.  Journ.,  1858), 
are  said  to  have  proved  fatal. 


SOMNIFACIENTS.  141 

Paregoric  (TiNCTURA  OPII  CAMPHORATA,  U.  S. )  has  in  a  fluid- 
ounce  i.  85  grains  of  opium,  besides  benzoic  acid,  oil  of  anise,  and  camphor  ; 
in  consequence  of  the  last  ingredient,  it  is  more  constipating  than  are  the 
other  preparations  of  opium,  and  hence  is  preferred  in  diarrhoea-mixtures. 
It  is  also  much  used  in  cough-mixtures.  Dose,  fei  to  f^i  (3.75-30 
C.c. ).  The  other  liquid  preparations  all  now  represent  ten  per  cent,  of 
powdered  opium  by  weight,  and  may  be  given  in  doses  of  ten  to  fifteen 
minims  (0.6-0.9  C.c.).  The  deodorized  tincture  (TINCTURA  OPII  DE- 
ODORATI,  U.  S. )  contains  no  narcotine,  and  none  of  the  odorous  principle 
of  opium.  It  therefore  is  less  apt  to  cause  nausea  than  are  the  other 
preparations.  Its  drop  almost  equals  the  minim  in  size.  The  other 
preparations  are — TINCTURA  OPII,  U.  S.,  or  Laudanum  (one  hundred 
and  twenty  drops  to  the  fluidrachm)  ;  TINCTURA  IPECACUANHA  ET  OPII, 
U.  S.,  VINUM  OPII,  U.  S. ,  or  Sydenham's  Laudanum  (formerly  ^i  to  £51)  ; 
ACETUM  OPII,  U.  S. ,  or  Black  Drop. 

MORPHINA.     U.  S. 

This  alkaloid  occurs  in  minute,  colorless,  shining  crystals,  according 
to  Guy  melting  at  330°  F.  and  subliming  at  340°  F.  ;  insoluble  in  cold 
and  nearly  so  in  boiling  water  ;  only  slightly  soluble  in  cold  alcohol  and 
ether  ;  freely  soluble  in  boiling  alcohol  and  in  the  fixed  and  volatile  oils. 

The  Morphine  Acetate  (MORPHINE  ACETAS),  Sulphate  (MORPHINE 
SULPHAS),  and  Hydrochlorate  (MURIATE  OF  MORPHINE,  MORPHINE 
HYDROCHLORAS)  are  all  official.  The  first  is  a  white  powder  ;  the  last 
two  occur  snow-white  in  feathery  crystals.  They  are  soluble  in  water,  of 
a  bitter  taste,  and  physiologically  and  therapeutically  equivalent. 

THERAPEUTICS. — The  salts  of  morphine  differ  in  their  therapeutic 
value  from  opium  chiefly  in  that  they  act  with  less  power  as  sudorifics 
and  in  checking  secretion  in  the  bowels,  and  consequently  are  less  con- 
stipating. The  smallness  of  their  dose  and  their  perfect  solubility  fit 
them  for  hypodermic  use.  Almost  the  only  purpose  for  which  they  are 
used  in  this  way  is  to  relieve  pain.  The  advantages  of  the  method  are 
the  quickness  of  the  results  and  the  increased  power  of  relieving  suffering 
which  the  remedy  seems  to  acquire.  In  cases  of  severe  pain  hypoder- 
mics are  invaluable  ;  but  it  must  be  borne  in  mind  that  sometimes  they 
cause  most  unpleasant  symptoms.  We  have  seen  very  alarming  results 
from  the  injection  of  one-sixth  of  a  grain,  which  dose  is  said  to  have 
caused  death.  In  females,  unless  very  robust,  the  maximum  dose  should 
be  one-eighth  of  a  grain  (0.008  Gm. )  ;  in  men,  one-sixth  to  one-quarter 
(0.01-0.016  Gm.).  The  dose  of  a  salt  of  morphine  corresponding  to  a 
grain  of  opium  is  one-quarter  of  a  grain. 

CODEINA.     U.  S. 

Codeine  Sulphate  (  Codeina  Sulphas,  U.  S. )  and  Phosphate  (  Codeince 
Phosphas,  U.  S. )  have  the  advantage  over  the  alkaloid  of  greater  solu- 
bility, the  latter  dissolving  in  two  and  a  quarter  parts  of  water. 

According  to  the  statements  of  various  observers,  codeine  produces 
in  the  lower  animals  symptoms  very  similar  to  those  caused  by  morphine, 


I42  GENERAL  REMEDIES. 

— namely,  in  the  frog,  heightened  reflexes,  tetanic  cramp  with  convul- 
sions, also  coma  ;  in  the  pigeon,  restlessness,  disturbances  of  respiration, 
violent  convulsions  ;  in  the  dog,  disturbances  of  respiration,  languor,  con- 
vulsive twitchings,  also  sleep.  For  detailed  discussion  of  the  observations 
of  various  investigators,  see  tenth  edition  of  this  work. 

In  man  codeine  is  a  very  uncertain  and  feeble  hypnotic,  whose  action, 
especially  after  large  doses,  is  sometimes  attended  by  marked  restless- 
ness. The  statements  of  various  clinicians  as  to  its  effects  and  practi- 
cal value  vary  very  greatly,  the  variance  probably  depending  largely 
upon  the  quality  of  the  codeine  used,  in  many  cases  the  drug  exhibited 
having  in  all  probability  been  contaminated  with  morphine.  In  S.  Weir 
Mitchell's  "experiments  upon  himself  five  grains  produced  no  symptoms 
except  slight  increase  in  the  pulse-rate,  nausea,  some  giddiness,  and  a 
sense  of  heaviness  about  the  head  ;  results  which  are  in  accord  with  the 
earlier  experiments  of  Harley.  Contrariwise,  A.  S.  Myrtle18  records 
a  case  of  severe  poisoning  caused  by  four  grains  of  codeine.  There  was 
first  vascular  excitement  and  exhilaration,  then  depression  with  great 
anxiety,  nausea  and  vomiting,  pale,  cool,  clammy  skin,  slight  contraction 
of  pupil,  and  sleeplessness,  with  slight  delirium.  Two  cases  of  serious 
poisoning  by  eight  grains  have  been  reported.* 

In  our  experience  codeine  has  proved  to  be  a  practically  useless  rem- 
edy except  in  doses  of  half  a  grain  for  the  purpose  of  controlling  bron- 
chial irritation  in  phthisis  and  other  diseases.  The  dose  of  the  alkaloid 
may  be  set  down  as  from  half  a  grain  to  two  grains  (0.03-0.13  Gm. ), 
but  in  the  administration  of  the  larger  amount  the  practitioner  should  be 
sure  he  has  a  preparation  that  does  not  contain  morphine. 

In  former  editions  of  this  treatise  the  non-official  opium  alkaloids  narceine, 
narcotine,  thebaine,  papaverine,  laudanine,  porphyroxine,  anarcotine,  and  crypto- 
pine  were  discussed  at  length,  but,  as  they  have  failed  entirely  to  come  into  use  as 
therapeutic  agents,  their  consideration  is  here  omitted :  a  full  summary  of  our 
knowledge  of  their  physiological  action  may  be  found  in  the  tenth  edition  of  this 
work. 

MORPHINE  DERIVATIVES. 

Various  derivatives  of  the  alkaloid  morphine  are  physiologically  active, 
but  only  two  of  them  are  at  present  used,  PERONINE  (morphine  benzyl- 
ester  hydrochloride),  an  account  of  which  may  be  found  in  previous  editions 
of  this  book,  having  fallen  into  complete  desuetude. 

DIONINE  (mono-ethyl-ester  of  morphine  hydrochloride}  is  a  white  crys- 
talline powder,  soluble  in  seven  parts  of  water.  Although  no  careful 
physiological  research  has  been  made  upon  it,  it  appears  to  share  to  a 
slight  extent  the  analgesic  and  hypnotic  powers  of  morphine,  and  not 
ordinarily  to  produce  nausea,  constipation,  or  other  disagreeable  after- 
effects. It  is  affirmed  to  be  more  active  than  morphine  in  the  sup- 

*  See  Brit.  Med.  Journ.,  1888,  ii.,  and  New  York  Med.  Record,  1893,  xliv. 


SOMNIFACIENTS.  143 

pression  of  cough,  and  to  be  also  actively  antihydrotic,  so  that  it  is  of 
especial  value  in  advanced  pulmonary  tuberculosis.  It  has  also  been  com- 
mended in  asthma  and  as  an  anaphrodisiac  ;  also  in  dysmenorrhcea.  The 
dose  is  from  one-quarter  to  one-half  a  grain  in  powder,  pill,  or  solution. 
The  general  professional  verdict  seems  to  be  that,  on  the  whole,  it  resem- 
bles heroine  in  its  therapeutic  value,  but  is  less  powerful. 

Local  Effect. — As  first  noted  by  Wolffberg,  one  drop  of  a  two  per  cent, 
solution  of  dionine  placed  upon  the  conjunctiva  immediately  produces 
smarting  and  burning  pain,  free  lachrymation,  marked  injection  of  the  con- 
junctival  blood-vessels,  chemosis  of  the  conjunctiva,  and  occasionally  swell- 
ing of  the  lid.  This  ' '  dionine  reaction  ' '  varies  very  much  ;  sometimes  it 
almost  fails  to  appear.  Under  these  circumstances  a  stronger  solution,  for 
example,  five  to  ten  per  cent.,  will  usually  avail,  or,  according  to  Darier, 
an  even  more  active  effect  may  be  produced  if  a  morsel  of  powdered 
dionin  is  used,  or  if  the  solution  is  injected  beneath  the  conjunctiva.  The 
irritative  effects  of  the  drug  are  at  times  exceedingly  violent,  and  Darier 
believes  that  the  edema  of  the  conjunctiva,  and,  moreover,  one  that  spreads 
to  the  lids  and  tissues  of  the  face,  is  more  pronounced  in  the  subjects  of 
vascular  disease,  nephritis  and  scrofula.  The  dionine  reaction  takes  place 
in  the  normal  as  well  as  in  the  diseased  eye.  Usually  it  subsides  materi- 
ally within  an  hour.  It  may  continue  for  a  number  of  hours,  although 
the  pain  and  smarting  almost  always  disappear  in  a  very  short  space  of 
time,  to  be  followed  by  a  period  of  analgesia  lasting  for  several  hours. 

The  phenomena  of  dionine  reaction  have  been  aptly  described  by 
Wolffberg  by  the  term  "lymphatic  inundation,"  and  Darier,  who  is 
particularly  enthusiastic  in  his  recommendation  of  the  value  of  this  medi- 
cament, thinks  that  lymphatic  inundation  washes  out  not  only  the  sur- 
face of  the  eyeball  but  also  the  subconjunctival  and  intracorneal  lymph- 
spaces,  and  perhaps  even  the  intraocular  spaces.  There  is,  according  to 
this  author,  not  only  an  afflux  of  liquid  but  also  of  lymphocytes,  whose 
duty  he  believes  is  concerned  with  the  defence  of  the  parts,  so  that  there 
is  a  more  active  production  of  antitoxins  and  phagocytes.  Whether  the 
drug  really  has  an  action  upon  the  diseased  processes  of  the  eye  them- 
selves and  aids  its  resolvent  power  by  a  subtraction  of  pathologic  fluid, 
or  whether  its  influence  should  be  regarded  as  that  of  a  counter-irritant, 
or  whether  it  depends  upon  its  power  of  increasing  lymphatosis,  has  not 
been  decided,  and  at  present  it  is  probably  not  possible  to  say  that  it  does 
more  than  stimulate  the  lymphatic  and  vascular  circulation  of  the  eye. 
So  far  as  I  am  aware,  the  only  untoward  recorded  result  from  its  action  is 
one  case  of  macular  hemorrhage  in  practice.  Violence  of  reaction  without 
ultimate  bad  results  is  not  an  uncommon  phenomenon. 

Its  indications  in  ophthalmic  therapeutics  are  numerous,  and  in  general 
terms  it  may  be  stated  that  it  has  a  favorable  influence  in  alleviating  pain- 
ful inflammations  of  the  anterior  portion  of  the  eye,  and  in  relieving  the  dis- 
tress incident  to  increased  intraocular  tension,  that  is,  glaucoma.  There  is 
much  evidence  to  show  that  it  facilitates  the  absorption  of  atropine,  eserine, 


I44  GENERAL  REMEDIES. 

pilocarpine,  etc.  It  is  useful  in  iritis,  irido-cyclitis,  simple  and  infected 
corneal  ulcers,  herpes  of  the  cornea,  superficial  and parenchymatous  kera- 
titis,  and  in  the  various  types  of  glaucoma.  There  is  some  evidence  that 
it  is  of  value  in  deeper  inflammatory  processes,  for  example,  in  uveitis, 
and  it  certainly  relieves  post-operative  inflammation  and  infection.  It 
would  seem,  according  to  an  observation  of  Dr.  Callan,  which  I  think  I 
can  confirm  from  personal  experience,  that  it  facilitates  the  regeneration 
of  corneal  tissue.  It  may  be  suitably  combined  with  cocaine,  atropine,  ese- 
rin  or  pilocarpine  where  these  drugs  are  also  indicated  ;  but  I  believe  that 
a  better  result  is  reached  if  the  dionine  is  used  separately,  and  the  atropin, 
cocaine,  etc.,  is  instilled  immediately  afterwards.  In  a  very  brief  time, 
usually  after  the  third  or  fourth  day  of  its  use,  the  eye  establishes  a  species 
of  immunity,  and  the  dionine  reaction  almost  fails  to  appear.  Therefore 
it  should  be  used  for  two  or  three  days,  and  then  omitted  for  three  days, 
when  again  the  reaction  is  likely  to  appear,  or,  if  it  does  not  appear,  the 
strength  of  the  solution  may  be  increased. 

It  is  the  practice  of  some  surgeons,  following  Darier's  recommenda- 
tion, to  use  a  five  per  cent,  solution.  If,  however,  this  occasions  too 
much  reaction,  in  my  own  experience  a  one  per  cent,  solution  acts  favor- 
ably, and  I  have  almost  abandoned  the  employment  of  the  stronger  prep- 
arations, except  when  a  very  decided  reaction  is  desirable,  or  when  im- 
munity has  been  secured.  Instead  of  employing  dionine  in  solution,  it  may 
be  used  in  powder,  for  example,  a  twelfth  of  a  grain,  or  the  powder  may 
be  dusted  directly  upon  an  ulcerated  surface.  With  this  method  of  em- 
ployment, recommended  by  Darier,  I  have  had  little  experience.  I  have 
also  not  prescribed  it  as  a  salve,  although  this  method  of  employment  has 
been  advised  and  commended  by  others.  Darier  has  used  it  subconjunc- 
tivally,  combining  it  with  a  physiological  salt  solution  under  these  circum- 
stances, by  injection.  The  reaction  is  very  violent ;  but,  for  example,  in 
detachment  of  the  retina,  is  said  to  be  of  service. 

The  asserted  power  of  dionin  of  clearing  up  corneal  scars  I  believe  to 
be  doubtful,  but  it  certainly  is  effective  and  very  useful  in  certain  inter- 
stitial deposits,  such  as  those  of  interstitial  keratitis,  both  in  the  early  and 
in  the  late  stages  of  the  disease.  The  solutions  should  be  freshly  pre- 
pared to  be  of  service.* 

HEROINE  (diacetic  ester  of  morphine},  which  occurs  as  a  colorless, 
odorless,  bitterish  crystalline  powder,  is  nearly  insoluble  in  water,  but 
forms  a  hydrochlorate  which  is  freely  soluble  both  in  water  and  in  alcohol. 
According  to  Dreser,49  confirmed  by  Strube,50  it  produces  in  the  lower 
animals  stupor  with  convulsions,  but  has  very  little  influence  upon  the 
circulation.  Ott51  has  found  that  in  the  frog  it  lessens  reflex  activity,  and 
in  sufficient  doses  causes  complete  paralysis  which  is  independent  of  any 
effect  upon  the  motor  nerve  or  muscle. 

*  This  account  of  the  local  effect  and  of  the  ophthalmic  use  of  dionin  was  written  by 
Professor  George  E.  de  Schweinitz. 


SOMNIFACIENTS.  145 

All  observers  are  in  accord  that  it  has  very  little  action  on  the  circu- 
lation. According  to  Ott,  in  doses  of  from  one-twentieth  to  one-tenth  of 
a  grain  it  produces  in  the  rabbit  slight  elevation  of  the  pressure  without 
much  change  in  the  pulse-rate.  The  dominant  action  of  heroine  is  upon 
the  respiratory  centre.  Both  Impens 52  and  Marshall 5S  state  that  in  small 
doses  it  slows  the  rate  but  slightly  increases  the  depth  of  the  respiration, 
while  in  large  amounts  it  lessens  both  the  frequency  and  the  depth.  Accord- 
ing to  Impens,  heroine  does  not  diminish  the  irritability  of  the  respira- 
tory centre  towards  carbonic  acid,  as  do  both  morphine  and  codeine  ;  this 
statement  is,  however,  in  direct  conflict  with  Dreser. 

From  the  experiments  of  Impens  and  Mayor  there  can  be  little  room 
for  doubt  that,  at  least  as  regards  the  lower  animals,  it  requires  less  heroine 
to  kill  than  it  does  morphine.  It  is  probable  that  this  statement  holds 
true  also  for  the  human  being.  As  has  been  pointed  out,  however,  by 
Impens  and  by  Morel-Lavallee,54  heroine  is  a  less  dangerous  drug  than 
morphine,  because  the  efficient  dose  is  disproportionately  smaller  than  the 
fatal  dose  in  comparison  to  morphine.  In  other  words,  although  it  re- 
quires about  half  the  quantity  of  heroine  that  it  does  of  morphine  to  kill, 
it  requires  only  about  one-fourth  of  the  quantity  to  exercise  its  maximum 
sedative  effect  upon  the  respiratory  centre. 

Toxic  symptoms  following  the  use  of  heroine  are  uncommon.  Two  and  a  half 
grains  are  said  to  have  produced  in  an  asthmatic  adult  syncope,  myosis,  blindness, 
and  subnormal  temperature,  lasting  for  many  hours,55  and  Dover  reports  great 
prostration,  dilated  pupils,  with  mental  aberration,  produced  by  three  grains. 
Thompson M  reports  death  in  a  case  of  severe  mitral  disease,  which  he  attributed 
to  heroine.  In  a  few  instances  nausea  and  vomiting  have  followed  the  use  of  heroine, 
perhaps  due,  as  claimed  by  Robinson,  to  some  chemical  change  in  the  drug.  In  a 
number  of  cases  heroine  has  caused  constipation. 

As  an  hypnotic  or  analgesic  heroine  is  certainly  very  much  inferior  to 
morphine,  but  it  has  the  advantage  that  in  chronic  cases  it  does  not  pro- 
duce the  agreeable  sensations  which  render  the  latter  drug  so  dangerous. 
In  arresting  cough  it  has  seemed,  in  our  experience  at  least,  equal  to  mor- 
phine in  activity,  and  has  the  great  advantage  of  not  checking  secretion 
either  in  the  lungs  themselves  or  in  the  alimentary  canal.  According  to 
Strauss,57  it  has  distinct  anaphrodisiac  properties,  making  it  useful  in  vari- 
ous forms  of  sexual  excitement,  such  as  nymphomania  and  masturbation. 
It  has  been  recently  asserted,  especially  by  E.  Elischer,58  that  it  is  so 
active  as  a  local  analgesic  that  one-quarter  of  a  grain  introduced  into 
the  vagina  will  relieve  the  suffering  even  of  uterine  cancer.  Rosenberg 
commends  a  two  and  a  half  grains  to  the  fluidounce  solution  as  a  local 
anaesthetic  in  diseases  of  the  throat,  and  especially  in  laryngeal  tuberculosis. 
When  there  is  excessive  cough,  as  in  asthma,  bronchitis,  whooping-cough, 
heroine  is  a  very  valuable  drug  ;  \\\ phthisis  it  has  the  further  virtue  of  reduc- 
ing the  tendency  to  sweating.  Dose,  from  one  tenth  to  one-third  of  a  grain 
(0.007-0.023  Gm.).  The  hydrochlorate  may  be  used  hypodermically. 


146  GENERAL  REMEDIES. 

CHLORALUM  HYDRATUM.  U.  S.— CHLORAL  HYDRATE.  U.  S. 

Chloral,  which  is  itself  not  used  in  medicine,  is  an  oily  liquid  giving  off, 
at  the  ordinary  temperature,  pungent  fumes  ;  it  is  made  by  the  action  of 
chlorine  on  alcohol  ;  by  union  with  water  it  is  converted  into  a  hydrate. 

Chloral  Hydrate  is  a  volatile,  crystalline  solid,  of  a  hot,  burning  taste, 
insoluble  in  cold  chloroform,  but  very  soluble  in  water,  ether,  and  alcohol. 
It  usually  occurs  as  transparent,  colorless  tablets,  but  sometimes  in  acic- 
ular  or  even  in  rhomboidal  crystals. 

If  an  alkali  be  added  to  a  solution  of  chloral  hydrate,  it  breaks  up 
into  formic  acid  and  chloroform,  which  latter,  when  water  has  been  the 
solvent,  at  once  separates  in  the  form  of  oily  drops. 

Local  Action. — Chloral  is  distinctly  germicidal  and  antiseptic,  and 
was  at  one  time  used  to  some  extent  for  preserving  cadavers,  keeping 
urinals  pure,  and  allied  purposes.  As  shown  by  Keen,1  a  solution  of 
twenty  to  forty  grains  to  the  ounce  will  preserve  animal  tissues  almost  in- 
definitely without  interfering  with  their  microscopic  structure.  It  is  also 
somewhat  irritant  in  its  action,  and  after  a  time  sedative  to  the  sensory 
nerves,  and,  it  may  be,  to  all  tissues. 

Absorption  and  Elimination.  — Chloral  is  absorbed  with  great  rapidity, 
its  action  being  often  manifested  within  five  minutes  after  its  ingestion. 
It  circulates  through  the  body  as  chloral  ;  its  exact  fate  in  the  system 
has  not  been  determined,  but  it  probably  escapes  from  the  body  in  part 
unchanged  and  in  part  in  the  form  of  compounds.  It  was  recognized 
in  the  urine  by  A.  Tomascewicz2  by  means  of  the  delicate  isocyan- 
phenol  reaction  *  of  Hoffmann.  Feltz  and  Ritter 3  believed  that  they  had 
found  sugar  in  the  urine  of  chloralized  animals,  but  Von  Mering  and  Mus- 
culus  and  F.  Echard  *  have  shown  that  the  substance  which  reduces  the 
copper  solution  will  not  undergo  fermentation,  and  Von  Mering  and  Mus- 
culus  have  separated  it,  as  urochloralic  acid,  in  colorless,  shining  needles, 
often  arranged  in  star-like  groups,  soluble  in  water  and  in  alcohol,  insol- 
uble in  ether.  The  existence  of  this  acid  has  been  confirmed  and  its 
chemical  properties  studied  by  A.  Borntraeger5  and  by  E.  Kiilz,6  who 
found  it  to  be  physiologically  inert. 

PHYSIOLOGICAL  ACTION. — General  Action. — When  chloral  is  given 
to  man  or  other  mammals  in  moderate  doses,  the  most  prominent  result 
in  the  great  majority  of  instances  is  a  quiet  sleep,  as  closely  allied  as  pos- 
sible to  natural  sleep.  The  subject  can  readily  be  aroused  from  the 
lighter  degrees  of  this,  waking  to  full  consciousness,  but  soon  dropping  off 
again  when  left  quiet.  The  pulse  is  in  this  degree  of  action  not  affected, 
or  is  rendered  a  little  slower  ;  the  pupil  is  contracted,  but  becomes  nor- 
mal so  soon  as  the  subject  is  awakened  ;  the  respiration  is  deep,  full,  and 
regular.  When  larger  amounts  are  given,  the  sleep  is  much  deeper,  and 
may  pass  into  profound  coma  ;  the  respirations  fall  in  number  ;  the  pulse 

*  Many  chemists  have  failed  to  find  chloral  for  want  of  a  delicate  test.  F.  Ogston 
(Edinb.  Med.  and  Surg.  Journ.,  xxiv.  292)  affirms  that  ammonium  sulphide  affords  a 
means  of  recognizing  minute  amounts  of  the  drug. 


SOMNIFACIENTS.  147 

is  weakened  and  rendered  slower,  but  may  become  rapid  and  irregular  if 
the  dose  has  been  toxic  ;  the  temperature  is  reduced  ;  the  muscular  sys- 
tem is  relaxed,  and  both  sensibility  and  reflex  action  are  diminished.  If 
a  fatal  dose  has  been  taken,  all  these  symptoms  are  intensified  :  with 
coma,  intense  muscular  relaxation,  weak,  thready  pulse,  and  a  pupil 
contracted  at  first,  but  afterwards  dilated,  the  victim  gradually  sinks  into 
death,  paralyzed  and  anaesthetic.  The  immediate  cause  of  death  is  usu- 
ally a  centric  paralytic  arrest  of  respiration  ;  but  in  many  cases  there 
appears  to  be  a  simultaneous  arrest  of  the  cardiac  action,  and  it  is  prob- 
able that  fatal  syncope  may  at  times  occur.  At  the  post-mortem  exami- 
nation, congestion  of  the  meninges  and  substance  of  the  brain  and  cord, 
and  of  the  lungs,  is  commonly  found.  The  blood  is  thought  by  Richard- 
son '  to  coagulate  less  firmly  than  when  normal. 

The  most  constant  and  prominent  of  all  the  symptoms  produced  by 
moderate  doses  of  chloral  is  sleep  :  this  is  without  doubt  due  to  a  direct 
action  of  the  drug  upon  the  cerebrum.  In  most  cases,  as  already  stated, 
it  is  quiet,  but  sometimes  it  is  restless,  and  in  man  has  occasionally  even 
been  wildly  delirious,  although  it  is  somewhat  uncertain  whether  the 
latter  condition  may  not  have  been  due  to  impurities  in  the  drug.  It 
seems  to  be  well  established  that  in  the  milder  degrees  of  this  sleep  there 
is  no  anaesthesia.  We  have  seen  the  hyperaesthesia  *  spoken  of  by  De- 
marquay8  after  small  doses  of  chloral,  and  there  can  be  no  doubt  that  it  is 
an  occasional,  if  not  a  constant,  phenomenon.  Rajewsky9  states  that 
there  is  in  frogs  a  corresponding  period  of  over-excitability  of  the  reflex 
centres,  and  that  in  rabbits  he  has  noticed  a  glowing  heat  borne  without 
much  complaint,  when  pinching  would  produce  violent  outcries.  In  very 
large  doses  chloral  produces  anaesthesia  ;  but,  unless  the  amount  em- 
ployed be  so  great  as  to  be  toxic,  this  anaesthesia  is  in  most  cases  very 
trifling. 

Motor  System. — The  paralysis  and  loss  of  reflex  excitability  induced 
by  chloral  are  not  muscular  in  their  origin,  for  Labbee  has  found  that 
after  death  the  muscles  respond  perfectly  to  galvanism.  Both  Labb£e 
and  Rajewsky  have  found  that  the  motor  nerves  are  in  no  wise  affected 
by  large  or  even  fatal  doses  of  chloral,  which  must  therefore  act  upon  the 
spinal  cord  to  produce  the  paralytic  phenomena.  The  experiments  of 
Rajewsky  have  afforded  positive  confirmation  of  the  conclusion  arrived  at 
by  this  process  of  exclusion  ;  for  he  found  that  in  the  latter  stages  of 
chloral-poisoning  direct  irritation  of  the  spinal  cord  gave  rise  to  much  less 
severe  spasms  than  in  the  unpoisoned  animal.  Before  this  paralytic  stage 
is  reached,  as  already  stated,  Rajewsky  affirms  that  in  the  frog  there  is  a 
period  of  increased  reflex  activity,  and  that  at  this  time  stimulation  of  the 
spinal  ganglia  shows  that  they  are  more  susceptible  than  normal.  The 


*  Bouchut  (New  York  Med.  Gazette,  Dec.  1870),  Dieulafoy  and  Krishaber  (Amer. 
Journ.  Med.  Sci.,  Jan.  1870),  Giovanni  and  Ranzoli  (Schmidt's  Jahrbucher,  cli.),  and 
Rajewsky  (Ibid.)  confirm  this,  while  Liebreich  and  Labb£e  deny  it ;  Hammarsten,  who 
has  noticed  such  hyperaesthesia,  is  inclined  to  think  it  apparent  rather  than  real. 


I48  GENERAL   REMEDIES. 

observer  last  named  states  that  these  phenomena  occur  just  as  freely  after 
destruction  of  Setschenow's  centre  in  the  frog  as  before,  and  are  there- 
fore independent  of  it. 

Circulation. — According  to  Demarquay,  when  chloral  has  been  ad- 
ministered to  animals  there  is  evident  enlargement  and  engorgement  of 
all  their  blood-vessels  ;  and  Rajewsky  states  that  he  has  found  sinking  of 
the  blood-pressure  in  rabbits  caused  by  small  as  well  as  large  doses  of  the 
drug.  On  the  other  side,  Labbe"e10  asserts  that  the  rabbit's  ear  grows 
pale  after  the  injection  of  a  very  feeble  dose.  In  man,  Bouchut  has  ob- 
tained sphygmographic  traces  which  he  thinks  indicate  a  primary 
increased  arterial  tension.  Nancias,  of  Venice,  has  found  the  tension 
normal,  but  Anstie  and  Andrews u  confirm  the  results  of  Bouchut  when 
small  doses  are  employed.  Preisendorfer,12  in  a  series  of  sphygmographic 
studies,  thought  that  there  might  be  a  brief  primary  rise  of  arterial  press- 
ure in  man,  as  in  animals,  but  under  the  full  action  of  chloral  the  arterial 
pressure  steadily  sinks.  We  do  not  think  that  much  confidence  is  to 
be  attached  to  the  clinical  observations  of  Bouchut  and  of  Anstie  and 
Andrews,  since  the  sphygmograph  seems  to  be  an  entirely  unreliable 
instrument  when  used  for  the  comparative  study  of  arterial  pressure  ;  and 
in  confirmation  of  the  statements  of  Rajewsky,  David  Cerna  has  found  in 
our  own  laboratory  that  it  is  not  possible  in  curarized  animals  to  elevate 
arterial  pressure  with  any  dose  of  chloral,  so  that  if  any  rise  of  pressure 
(as  seems  improbable)  is  ever  produced  in  the  normal  man  or  animal  by 
chloral,  such  rise  must  be  indirect  and,  probably,  due  to  respiratory  dis- 
turbance. Very  large  doses,  according  to  both  Andrews  and  Da  Costa," 
decidedly  lessen  arterial  pressure.  The  characteristic  influence  of  thera- 
peutic, and  still  more  of  toxic,  doses  is  to  produce  a  fall  in  the  blood- 
pressure,  usually  accompanied  by  a  lessening  in  the  frequency  of  the 
heart's  action,  which  Cerna  believes  to  be  largely  due  to  an  influence  upon 
the  cardio-inhibitory  centres  ;  although  Rajewsky  affirms  that  the  slowing 
of  the  pulse  in  the  frog  and  in  the  rabbit  is  produced  after  section  of  the 
inhibitory  nerves,  and  is  therefore  independent  of  them.  The  fall  of 
blood -pressure  is  probably  owing  in  part  to  the  vaso-motor  paralysis,  but 
perhaps  in  largest  part  to  depression  of  the  heart.  The  vaso-motor  palsy 
is  probably  chiefly  caused  by  an  action  upon  the  dominant  centre,  but 
Robert u  has  shown  that  there  is  also,  after  a  very  large  dose  of  the 
chloral,  palsy  of  the  coats  of  the  vessels.  When  toxic  doses  have  been 
employed,  the  heart,  after  numerous  pauses,  is  finally  arrested  in  diastole. 
Analogy  indicates  very  strongly  that  this  arrest  is  due  to  a  direct  influence 
upon  the  heart-muscle  or  ganglia,  and  the  researches  of  Sidney  Ringer 
and  H.  Sainsbury 15  and  of  David  Cerna 1S  seem  to  demonstrate  (the  con- 
trary results  obtained  by  Labb6e  notwithstanding)  that  when  chloral  is 
brought  in  direct  contact  with  the  isolated  heart  of  the  frog  there  is  an 
immediate  and  persistent  loss  of  power,  ending  finally  in  diastolic  arrest. 

In  poisoning  in  man,  the  pulse  has  towards  the  last  been  very  feeble, 
generally  rapid  and  irregular,  and  even  in  some  cases  in  which  recovery 


SOMNIFACIENTS.  149 

has  occurred  it  has  been  altogether  absent  for  a  time.  The  experiments 
of  Ringer  and  Sainsbury  are  so  concordant  with  this  that  it  appears  to  be 
established  that  chloral  is  a  direct  depressant  to  the  heart,  which  is  capable  of 
suddenly  and  unexpectedly  destroying  life,  precisely  as  does  chloroform. 

Respiration. — In  full  doses,  chloral  lessens  the  number  of  respirations 
per  minute,  causing  them  to  become  slow  and  full  ;  when  toxic  doses  are 
taken  this  action  becomes  more  and  more  marked,  the  rhythm  is  much 
affected,  and  the  respiration  grows  markedly  irregular,  and  sometimes  very 
rapid  and  shallow,  until  it  ceases.  As  these  phenomena  occur  equally 
after  section  of  the  vagi  (Rajewsky),  the  influence  of  chloral  must  be 
exerted  upon  the  respiratory  centre  at  the  base  of  the  brain. 

Tissue  Change. — Charles  Richet"  has  found  that  toxic  doses  of 
chloral  reduce  very  greatly  the  elimination  of  carbonic  acid,  at  the  same 
time  that  they  lower  the  bodily  temperature.  So  far  as  large  doses  are 
concerned,  A.  Gritzka18  is  in  accord  with  this,  although  he  asserts  that 
small  doses  increase  carbonic  acid  elimination.  It  is  plain  that  the  pro- 
found muscular  quiet  produced  by  chloral  must  lead  to  lessened  oxida- 
tion. Julius  Peiser19  affirms  that  chloral  increases  the  degeneration  of 
albuminous  tissues. 

Abdominal  Action. — Clinically  chloral  has  no  perceptible  action  upon 
the  gastro-intestinal  mucous  membrane,  save  as  a  local  irritant ;  but,  ac- 
cording to  the  experiments,  of  Wertheimer "°  and  Lepage 21  and  of  Charles 
Dubois,  it  increases  in  the  animals  both  pancreatic  and  biliary  secretion, 
chiefly,  but  not  altogether,  as  the  result  of  its  local  influence  in  the  duo- 
denum and  jejunum. 

Temperature. — A  most  remarkable  action  of  chloral  is  upon  the  tem- 
perature :  in  this  point  all  observers  are  in  accord  with  Richardson,  of 
London,  who  has  seen  the  temperature  fall  6°  F.  in  a  rabbit  which 
recovered.  Bouchut  has  noticed  a  fall  of  2°  (C.  ?)  in  an  infant,  and 
Da  Costa  and  other  observers  have  noticed  slighter  reductions  of  tem- 
perature in  man  after  therapeutic  doses.  In  a  case  reported  by  Levin- 
stein,22 after  six  drachms  of  chloral  the  temperature  rose  to  39.5°  C. 
(102.1*  F. ),  and  subsequently  fell  to  32.9°  C.  (91.22°  F. ).  Ham- 
marsten  has  found  that  the  fall  of  temperature  is  very  rapid,  6°  C.  in  an 
hour,  and  that  it  occurs  in  animals  well  wrapped  up  and  laid  in  a  warm 
place. 

SUMMARY. — Upon  the  cerebrum  chloral  acts  as  a  powerful  hyp- 
notic ;  in  full  doses  it  acts  as  a  depressant  upon  the  centres  at  the  base 
of  the  brain  and  upon  the  spinal  cord :  it  causes  slowing  and  weak- 
ness of  the  heart's  action,  and  probably  vaso-motor  paralysis,  also 
centric  slowing  of  the  respiration,  -with  loss  of  reflex  activity,  muscular 
weakness,  and  some  anaesthesia,  all  of  spinal  origin ;  in  fatal  doses  it 
usually  produces  a  gradual  death  by  paralyzing  the  respiratory  centres 
in  the  medulla,  although  in  rare  cases  it  kills  suddenly  by  directly  par- 
alyzing the  heart,  which  always  stops  in  diastole.  Its  action  in  very 
small  doses  is  uncertain,  but  there  is  some  evidence  to  indicate  that 
it  irritates  or  stimulates  the  spinal  and  the  cardiac  centres.  On  the 


150  GENERAL  REMEDIES. 

vagi  and  on  the  motor  nerve-trunks  it  has  no  marked  influence.  It 
does  not  undergo  the  chloroformic  decomposition  by  the  alkali  of  the 
blood  or  in  the  system,  and  is  eliminated  as  uro-chloralic  acid. 

Action  as  Chloral. — Liebreich23  was  led  to  the  discovery  of  the  value 
of  chloral  as  a  practical  medicine  by  the  knowledge  of  the  fact  that  it  is 
converted  when  in  solution  by  alkalies  into  chloroform  and  formic  acid, 
and  the  expectation  that  chloroform  would  be  generated  by  the  alkalinity 
of  the  blood.  This  theory,  which  at  one  time  held,  has  been  so  com- 
pletely disproved  as  almost  to  have  been  lost  sight  of.  A  discussion  of 
it  may  be  found  in  full  in  the  tenth  edition  of  this  treatise.  Suffice  it  for 
the  present  to  say  that  it  is  proved  that  chloral  circulates  in  the  blood  as 
chloral,  that  no  conversion  of  it  takes  place  in  the  body  into  chloroform, 
and  that  the  symptoms  which  it  produces  are  distinct  from  those  caused 
by  chloroform  ;  chloral  producing  a  much  longer  and  more  intense 
sleep  than  does  the  proportionate  dose  of  chloroform,  but  having  a  very 
much  feebler  anaesthetic  influence  ;  and  further,  that  in  the  ' '  salt  frog, ' ' 
with  a  circulating  fluid  completely  neutral,  chloral  acts  precisely  as  in 
the  normal  frog  (Rajewsky). 

THERAPEUTICS. — The  results  of  the  clinical  use  of  chloral  are  in 
strict  accord  with  its  known  physiological  action.  The  indication  which 
it  most  usefully  meets  is  to  induce  sleep.  The  more  purely  nervous  the 
wakefulness  the  more  successful  the  remedy.  When  from  functional 
over- excitement  of  the  brain  due  to  excessive  mental  strain,  or  from  anxiety 
or  other  kindred  cause,  the  patient  cannot  sleep,  chloral  is,  probably,  the 
most  certain  of  the  hypnotics.  On  the  other  hand,  when  severe  pain 
causes  wakefulness,  chloral  is  of  very  little  value, — at  least  in  doses 
which  we  think  safe.  Sometimes  even  in  these  cases  sleep  will  come,  but 
it  will  very  often  be  a  restless,  troubled  sleep,  with  moaning  or  other 
indications  of  suffering  ;  and  it  may  be  that  the  patient  on  awaking  will 
complain  that  he  has  suffered  more  while  sleeping  than  when  awake. 

In  the  sleeplessness  occurring  at  times  during  convalescence  from  acute 
disease,  chloral  is  very  efficacious.  In  the  early  stages  of  fevers  it  is 
sometimes  of  advantage  ;  Russell M  recommends  it  especially  in  the 
-wild  delirium  of  typhus  in  its  earlier  stages.  In  advanced  fever-cases, 
when  the  symptoms  are  gravely  adynamic,  we  believe  that  the  use  of 
chloral  would  be  very  perilous.  In  delirium  tremens  it  often  induces 
sleep  readily,  but  not  rarely  it  fails,  even  in  large  dose.  In  the  sleepless- 
ness of  acute  puerperal  or  non-puerperal  -mania  there  is  abundant  testi- 
mony to  the  value  of  chloral.  It  must  not  be  forgotten  that  chloral  is  a 
dangerous  remedy  when  there  is  cardiac  weakness  ;  and  when  in  any  of 
the  diseases  just  spoken  of  there  is  reason  to  suspect  a  fatty  or  even  a 
feeble  heart,  great  care  must  be  exercised  in  the  administration  of  chloral. 
Under  such  circumstances  the  dose  of  fifteen  grains  should  not  be  ex- 
ceeded, and  should  not  be  repeated  more  than  once  unless  after  an  in- 
terval of  several  hours. 

The  second  indication  to  meet  which  chloral  may  be  employed  is  to 


SOMNIFACIENTS.  151 

relax  spasm.  For  this  purpose  it  has  been  used  with  advantage  in  puer- 
peral and  ur&mic  convulsions.  It  must  be  remembered  that  in  many  of 
these  cases,  although  next  to  chloroform  the  best  palliative,  it  is  only  a 
palliative,  and  must  be  used  merely  to  quiet  the  nervous  disturbance  until 
other  remedies  can  have  time  to  act.  In  tetanus  it  has  been  affirmed  that 
chloral  is  the  remedy.  Joseph  R.  Beck*5  has  collected,  of  the  traumatic 
form  of  the  disease,  thirty-six  cases,  with  twenty-one  recoveries,  in  which 
chloral  constituted  the  whole  or  the  major  part  of  the  treatment. 
References  *  are  given  below  to  fifty-six  cases  in  addition  ;  so  that  the 
figures  stand  forty-eight  recoveries  and  forty-four  deaths.  These  results 
do  not  seem  to  warrant  the  high  estimate  which  has  been  set  upon  the 
value  of  chloral  in  tetanus.  Very  extraordinary  results  have  been  ob- 
tained by  Macnamara26  in  tetanus  by  using  chloral  simply  at  bedtime 
(forty  grains),  with  an  occasional  dose  (thirty  grains)  in  the  morning 
when  there  is  high  temperature  ;  and  administering  brandy,  milk,  and 
eggs  very  freely  during  the  day.  Chloral  is  undoubtedly  a  valuable 
remedy  in  tetanus  and  in  strychnine-poisoning  ;  there  is,  however,  no 
reason  for  relying  upon  its  exclusive  use.f 

In  trismus  nascentium,  as  originally  recommended  by  Widenhofer," 
it  is  undoubtedly  very  valuable.  Widenhofer  gave  it  to  the  young  babe  in 
one-  and  two-grain  doses  by  the  mouth,  or,  when  the  spasms  prevented,  in 
double  the  quantity  by  the  rectum.  In  chorea  it  is  not  directly  curative, 
but  is  of  great  importance  when  it  is  essential  to  temporarily  check  the 
violence  of  the  movements.  As  a  nocturnal  quietant  and  hypnotic,  it  is 
of  the  highest  value  in  cases  of  acute  chorea  in  which  speedy  death  is 
threatened  from  the  incessant  and  violent  movements  ;  also  in  cases  com- 
plicated with  fractures,  where  a  temporary  lull  is  of  importance.  In 
puerperal  convulsions  its  use  in  large  doses  has  met  with  a  great  deal  of 
favor.  A  half-drachm  may  be  exhibited  at  once,  and  half  the  quantity 
every  hour  or  two  pro  re  nata. 

*  RECOVERY. — Fergusson  (Edin.  Med.  Journ.,  July,  1871)  ;  Watson  {Lancet,  1870) ; 
Bartlett ;  May  ;  Ballantyne ;  Gushing  (Pacific  Med.  and  Surg.  Journ.)  ;  Lovegrove  (Brit. 
Med.  Journ.,  1872,  493) ;  Herndon  (Atlanta  Med.  and  Surg.  Journ.,  1873,  69)  ;  Mac- 
namara (Indian  Med.  Gaz.,  April,  1871)  ;  Richelot  (Bulletin  Therap.,  Ixxxvi.) ;  Lucian 
Papillaud  (Gaz.  Medicale,  1875,  176)  ;  Bourdy  (Bull.  Therap.,  Ixxxvi.)  ;  Cane  (Lancet, 
1876.  i.  564) ;  Cauvy  (Bull.  Therap.,  xciii.  186) ;  Durand  (Centralbl.f.  Chirurgie,  1876, 
778) ;  Laurens  (Le  Progres  Med.,  1876,  180)  ;  Pugliese  (Journ.  de  Therap.,  1875,  244)  : 
each  one  case  ;  Cargile  (Lancet,  1877,  ii.  158),  three  cases ;  Boon  (London  Pract.,  xx.  161), 
two  cases  ;  Roberts  (Amer.  Journ.  Med.  Sci.,  Ixxiv.  420),  three  cases ;  Garnett  (Cincinnati 
Lancet  and  Clinic,  1880,  316),  two  cases. 

FATAL. — Porta  (Schmidt's  Jahrbucher,  cli.  no),  two  cases ;  Macnamara  (Indian  Med. 
Gaz.,  April,  1871),  six  cases;  Baudon  (Bulletin  Therap.,  Ixxxvi.),  three  cases;  Blin 
(Ibid.),  three  cases  ;  Petit  (Centralbl.f.  Chir.,  1876,792),  three  cases;  Roberts  (Amer. 
Journ.  Med.  Sci.,  Ixxiv.  420),  three  cases ;  Cruveilhier  (intravenous)  (Bulletin  Therap., 
Ixxxvi.) ;  Labbee  (Ibid.) ;  Itard  (Schmidt's  Jahrb.,  cli.) ;  Lannelongue  (Bulletin  Therap., 
1874,  Ixxxvii.) ;  Verneuil  (Ibid.,  1874,  Ixxxvii. ) ;  Boon  (London  Practitioner,  xx.  161) ; 
Boucquier  (Centralbl.f.  Chir.,  1876,  717) ;  Bresson  (Le  Progres  Med.,  1876,  180)  ;  Pug- 
liese  (Journ  de  Therap.,  1875,  244) :  each  one  case. 

t  For  a  paper  discussing  the  relations  of  chloral  to  various  mostly  unimportant  alka- 
loids, see  Arch.f.  Exber.  Path,  und  Therap.,  ix.  440. 


152  GENERAL  REMEDIES. 

In  the  convulsions  of  children  it  has  been  employed  with  apparent 
good  ;  in  cramps,  in  singultus,  in  the  spasmodic  nocturnal  enuresis  of 
children,  in  laryngismus  stridulus  and  other  spasmodic  affections  of  the 
glottis,  in  nocturnal 'emissions ;  in  whooping-cough,  and  in  all  forms  of  severe 
spasmodic  disorder  when  it  is  desired  temporarily  to  suppress  the  motor 
disturbance,  chloral  remains  the  standard  remedy.  In  asthma  it  has 
sometimes  been  of  use,  but  more  often  it  has  failed.  Its  hypodermic 
use  in  the  algid  stage  of  cholera,  as  recommended  by  Dr.  Hall,28  appears 
to  us  of  very  doubtful  value. 

The  third  indication  for  which  chloral  has  been  used  is  to  relieve  pain. 
That  it  will  do  so  when  given  in  very  large  doses  there  can  be  no  doubt  ; 
but,  unless  the  dose  be  so  large  as  to  be  dangerous,  chloral  is  of  little 
value  as  an  analgesic.  Its  powers  in  this  direction  are  incomparably  less 
than  those  of  opium,  and  its  habitual  use  is  attended  by  grave  dangers. 

As  originally  suggested  by  Lyon  Playfair,29  chloral  may  be  given  in  the 
early  stages  of  labor  to  lessen  the  severity  of  the  pain  ;  it  is  stated  also  to 
be  of  service  as  a  relaxant  when  there  is  rigidity  of  the  os.  Fifteen  grains 
may  be  administered  and  repeated  in  half  an  hour  if  necessary. 

Locally  a  solution  of  chloral  (ten  per  cent,  to  saturation)  has  been 
used  with  asserted  very  good  effects  as  a  stimulant  and  antiseptic  in  foul 
ulcers,  buboes,  bedsores,  etc.,  especially  when  the  discharge  is  free, — as  a 
haemostatic  when  there  is  oozing  of  blood, — and  as  an  antiseptic  and  local 
anaesthetic  in  uterine  and  other  cancers.  Applied  to  the  skin,  it  is  a 
powerful  irritant,  and  has  been  proposed  as  a  vesicant,*  but  is  said  to 
cause  excessive  pain.30 

The  intravenous  injection  of  chloral,  as  suggested  by  Or6,si  for  the 
purposes  of  anaesthesia,  and  for  the  combating  of  tetanic  spasms,  is  en- 
tirely unjustifiable  and  is  at  present  rarely  practised,  death  having  in 
various  cases  resulted  from  the  unexpected  violence  of  its  action  or  from 
the  coagulation  of  the  blood  which  it  produced. 

TOXICOLOGY. — The  minimum  fatal  dose  of  chloral  is  hardly  estab- 
lished, but  thirty  grains  have  produced  death.  (See  Administration.}  In 
very  many  cases,  however,  recovery  has  occurred  after  the  taking  of  sev- 
eral drachms  ;  indeed,  Eshleman  has  reported  recovery  after  the  inges- 
tion  of  four  hundred  and  sixty  grains.  There  are  no  pathognomonic 
lesions  found  after  death  from  chloral,  but  a  dark,  bloated  countenance 
and  other  evidences  of  death  from  asphyxia  have  been  noted. 

The  treatment  of  chloral-poisoning  is  identical  with  that  of  opium- 
poisoning,  consisting  in  the  free  use  of  internal  and  external  stimulants, 
such  as  sinapisms,  dry  heat,  frictions,  flagellations,  etc.,  to  maintain  the 
circulation,  and  of  shaking,  walking,  application  of  the  dry  electric  brush, 
cold  douches,  etc.,  to  keep  up  the  respiration.  In  practising  these 

•According  to  Bonnet  (Union  Pharm.,  xlii.  490),  one  gramme  of  chloral  hydrate, 
rubbed  up  with  oil  of  sweet  almonds  or  vaseline  and  spread  on  a  diachylon  plaster  twelve 
by  fifteen  centimetres  and  placed  on  the  skin,  will  in  fifteen  minutes  cause  burning 
pain,  after  which  time  it  should  be  removed  and  the  part  covered  with  cotton  wool. 
During  the  sleep  which  usually  follows  the  absorption  of  the  chloral  a  blister  will  form. 


SOMNIFACIENTS.  153 

measures  it  must  be  remembered,  however,  that  the  patient  in  chloral- 
poisoning  is  much  more  apt  to  die  of  exhaustion,  and  especially  of  cardiac 
failure,  than  in  opium-poisoning,  and  that  therefore  those  methods  of 
arousing  the  nerve-centres  which  do  not,  like  walking,  require  the  expendi- 
ture of  effort  on  the  part  of  the  patient  are  to  be  preferred.  Artificial  respi- 
ration should  always  be  resorted  to  before  natural  respiration  altogether 
fails,  and  Clemens 32  has  found  that  animals  asphyxiated  by  chloral  may 
often  be  at  once  aroused  by  the  inhalation  of  oxygen.  Atropine  and 
strychnine  are  important  remedies.  B.  W.  Stone 33  reports  recovery 
from  four  hundred  and  twenty-five  grains  of  chloral  after  the  hypodermic 
use  of  one-fifth  of  a  grain  of  strychnine  in  divided  doses.  Digitalis  may 
be  given  to  sustain  the  heart.  I.  M.  Booth  M  reports  a  case  of  recovery 
after  about  one  hundred  and  ten  grains  of  chloral  under  the  use  of  tincture 
of  belladonna.  Lauder  Brunton  K  has  shown  that  if  the  bodily  temperature 
be  maintained  artificially  animals  survive  doses  of  chloral  usually  fatal,  and 
in  human  chloral-poisoning  the  bodily  warmth  should  be  maintained  by 
the  use  of  dry  external  heat,  hot  blankets,  hot  baths,  and  other  devices. 

While  some  affections  have  been  erroneously  attributed  to  chronic 
chloral-poisoning,  there  seems  to  be  no  doubt  that  its  long-continued 
use  often  does  produce  serious  symptoms.  The  cases  are  divisible  into 
two  or  three  groups,  which  are,  however,  really  artificial,  as  is  shown  by 
the  occurrence  of  cases  belonging  to  two  or  even  three  of  the  groups. 
In  the  first  group  the  respiration  is  chiefly  affected.  The  dyspnoea  may 
be  slight,  and  may  only  be  felt  at  times,  as  after  exertion  or  after  meals  ; 
but  it  may  be  constant  and  alarming.  Cases  of  this  character  are  re- 
ported by  Jastrowitz,  by  Schule,  and  by  Ludwig  Kirn.36  In  one  instance 
(N.  R.  Smith37),  death  from  bronchial  effusion  is  belreved  to  have  been 
caused  by  chloral.  Kirn88  affirms  that  in  some  cases  mental  disturbance 
with  hallucinations  occurs. 

In  the  second  group  of  cases,  eruptions  of  the  skin  are  the  chief 
manifestations  of  the  toxaemia.  In  the  mildest  of  these  there  is  no 
distinct  rash,  only  the  occasional  appearance  of  transient  red  blotches  on 
the  face  or  neck.  But  a  very  extraordinary  tendency  exists  towards  the 
production  of  a  rash  or  discoloration  at  the  slightest  cause,  so  that  drink- 
ing a  glass  of  wine  will  produce  an  intense,  even  livid,  erythematous  red- 
ness of  the  face.  In  other  instances  there  is  marked  erythema  (Schule 89), 
occurring  first  in  spots  upon  the  face,  but  extending  downward  to  the 
trunk,  becoming  more  and  more  general,  and  showing  a  marked  ten- 
dency to  follow  the  nerve-trunks.  This  erythema  is  seemingly  due  to 
vaso-motor  weakness,  and  consequently  is  allied  to  other  more  urgent 
symptoms  seen  in  chloral  toxaemia.  Sometimes  it  invades  the  mucous 
membranes,  which  become  red,  swollen,  and  cedematous  ;  and  if  the 
glands  are  involved,  as  in  a  case  reported  by  Chapman,10  the  result  may 
be  serious.  A  deeper  implication  of  the  vaso-motor  and  cardiac  nervous 
system  was  probably  the  cause  of  the  general  oedema,  profound  weak- 
ness, and  failure  of  heart-action  in  the  case  recorded  by  N.  R.  Smith 


154  GENERAL  REMEDIES. 

{he.  «"/.),  and  possibly  also  of  the  desquamation  of  the  cuticle  and  ulcer- 
ations  about  the  nails  noted  in  some  of  his  cases  by  the  same  physician. 

In  the  third  group  of  cases,  petechiae,  ecchymoses,  ulcerations,  and 
even  high  fever  and  other  pyaemic  symptoms,  are  asserted  to  have  been 
produced  by  the  continuous  use  of  chloral.  It  seems  to  us,  however, 
very  doubtful  whether  the  drug  really  was  the  cause  of  the  sypmtoms 
which  have  been  recorded  by  Crichton  Brown,  by  Monkton,  and  by 
Kirn. 

The  habitual  use  of  chloral  as  a  narcotic  has  been  indulged  in,  it  is 
asserted,  to  a  considerable  extent,  and  George  F.  Elliott41  reports  symp- 
toms like  those  of  delirium  tremens  as  following  the  withdrawal  of  the 
accustomed  draughts. 

ADMINISTRATION. — Although  the  continuous  use  of  chloral  may  lead 
to  a  very  serious  chronic  poisoning,  we  have  no  knowledge  that  the  chloral 
itself  accumulates  largely  in  the  system  ;  and  it  certainly  has  no  cumu- 
lative action  like  that  of  digitalis,  in  which  a  sudden  outbreak  of  symp- 
toms occurs  without  warning.  On  the  other  hand,  the  single  large 
dose  of  chloral  in  rare  cases  acts  with  unexpected  violence.  It  has  fre- 
quently been  given  in  doses  of  thirty  grains.  That  this  is  not  entirely 
safe,  however,  is  shown  by  the  case  of  Reynolds,"  in  which  forty-five 
grains  caused  most  alarming  symptoms  ;  by  that  of  Watson,43  in  which 
eighty  grains,  given  in  ten-grain  doses  spread  over  thirty-six  hours, 
nearly  proved  fatal  ;  and  especially  by  a  number  of  cases  recorded  by  H. 
W.  Fuller,44  in  some  of  which  very  alarming  symptoms  followed  the  ex- 
hibition of  thirty  grains,  and  in  one  death  in  a  healthy  young  woman  of 
thirty.  Schwaighofer,45  of  Vienna,  records  coma  and  death  in  a  drunkard 
following  the  ingestion  of  half  a  drachm.  W.  H.  Lathrop46  details  the  case 
of  a  man  previously  healthy,  but  suffering  from  delirium  tremens,  who 
took  sixty  grains  between  12  and  i  P.M.,  at  2.30  P.M.  twenty  grains  more, 
and  at  3  P.M.,  no  effect  being  manifest,  twenty  grains  more.  His  physi- 
cians then  left  him  sleepless  and  complaining  only  of  a  slight  paralysis  of- 
the  lower  extremities  ;  and  almost  in  a  moment  he  was  dead.  Other 
cases  might  be  quoted,47  but  the  above  are  sufficient  to  show  that  chloral 
may  kill  suddenly  and  unexpectedly. 

An  observation  of  Vulpian48  throws  much  light  upon  these  sudden 
deaths.  He  found  that  galvanization  of  a  divided  vagus  would  cause  in 
a  chloralized  animal  not  momentary,  but  permanent,  arrest  of  respiration, 
if  the  centric  end  was  selected,  or  permanent  diastole  of  the  heart  if  the 
distal  part  of  the  nerve  was  attacked.  It  is  very  probable  that  in  a  man 
under  the  influence  of  chloroform  or  of  chloral,  death  may  be  precipitated 
by  a  slight  peripheral  inhibitory  irritation.  We  think  the  practical  deduc- 
tion from  the  known  facts  is  that  twenty  grains  (1.3  Gm.)  is  the  highest 
safe  dose  of  chloral  ;  that  this  amount  should  not  be  repeated  oftener 
than  once  an  hour,  and,  when  sixty  grains  have  been  taken,  not  again 
for  some  hours,  unless  in  very  urgent  cases,  as  acute  tetanus  or  violent 
chorea  threatening  speedy  dissolution. 


SOMNIFACIENTS.  155 

SULPHONMETHANUM.     U.S. 

Sulphonal  (di(sthylsulfondimethylmethane)y  discovered  by  E.  Bau- 
mann  in  1866,  belongs  to  the  group  of  rather  numerous  physiologically 
active  compounds  known  as  the  disulphones,  of  which  three  ethyl  com- 
pounds— namely,  sulphonal,  which  contains  two  ethyl  radicals  ;  trional, 
which  contains  three  ethyl  radicals  ;  tetronal,  which  contains  four  ethyl 
radicals — have  been  used  as  hypnotics  in  practical  medicine. 

The  original  statement  of  Baumann  and  of  Kast,  that  the  hypnotic 
powers  of  these  drugs  is  in  direct  relation  to  the  number  of  ethyl  radicals 
in  their  chemical  make-up,  has  been  confirmed  by  Diehl. 

Sulphonal,  which  was  first  physiologically  investigated  by  A.  Kast,1 
occurs  in  thick,  colorless  prisms,  soluble  in  from  eighteen  to  twenty  parts 
of  boiling  water,  not  soluble  in  one  hundred  parts  of  cold  water,  slightly 
soluble  in  ether,  benzol,  and  chloroform  ;  tasteless,  odorless,  and  of  very 
persistent  constitution. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Elimination. — Sulphonal 
is  not  at  all  irritant,  and,  indeed,  locally  it  appears  to  be  inert.  Owing 
to  its  great  insolubility  it  is  absorbed  very  slowly  from  the  stomach,  the 
method  of  its  absorption  being  at  present  unknown.  When  taken  in 
large  amount  it  escapes  to  some  extent  from  the  kidney  unchanged,  but 
the  greater  portion  of  it  is  converted  into  an  organic  sulphur  compound, 
which,  according  to  the  researches  of  W.  J.  Smith  (confirmed  by  Bau- 
mann and  Salkowski2),  is  probably  athyl-sulphonic  acid. 

General  Action. — The  symptoms  which  are  produced  in  man  by 
even  large  therapeutic  doses  of  sulphonal  are  simply  quiet  sleep,  out  of 
which  the  patient  wakes  after  some  hours  in  his  normal  condition,  or  not 
rarely  with  a  certain  amount  of  giddiness  and  lack  of  mental  tone. 
Probably  on  account  of  the  difficulty  of  its  absorption,  with  the  conse- 
quent escape  of  it  from  the  alimentary  canal,  sulphonal  has  very  rarely 
produced  death  when  taken  in  a  single  dose. 

In  one  case  recovery  occurred  after  one  hundred  and  twenty  grains,  although 
there  were  complete  abolition  of  the  reflexes  and  loss  of  the  radial  pulse.3  E. 
Neisser  *  has  recorded  a  case  in  which  one  hundred  grammes  caused  a  profound 
sleep  lasting  ninety  hours,  a  fall  of  bodily  temperature  to  96°  F. ,  and  a  symmetrical 
minutely  papulous  eruption  upon  the  hands,  but  no  great  disturbance  of  the  heart 
or  breathing  or  of  the  reflexes  ;  after  recovery  there  was  a  marked  ataxia  of  speech 
and  movement  which  disappeared  in  a  week. 

That  the  single  dose  of  sulphonal  may  prove  fatal  is,  however,  es- 
tablished by  the  following  cases  : 

Petitt 5  states  that  he  has  seen  coma  ending  in  death  produced  in  a  woman  by 
two  grammes.  In  a  case  recorded  by  G.  Hoppe-Seyler  and  Ritter6  fifty  grammes 
produced  death  in  seventy  hours,  the  symptoms  having  been  coma,  cyanosis,  and 
high  fever.  The  expired  air  had  the  odor  of  mercaptan,  and  the  urine  contained 
unaltered  sulphonal.  Pronounced  fatty  necrosis  of  the  intestinal  and  renal  epithe- 
lium, fatty  degeneration  of  the  heart,  and  broncho-pneumonia  were  found  in  the 


156  GENERAL  REMEDIES. 

body.  The  broncho-pneumonia  was  believed  by  Hoppe-Seyler  to  be  the  result 
of  the  aspiration  of  the  contents  of  the  mouth  and  gullet,  due  to  the  insensibility  of 
the  epiglottis. 

In  the  frog,  the  dog,  and  the  rabbit  sulphonal  produces  sleep,  which, 
if  the  dose  be  sufficiently  large,  deepens  into  coma,  and  is  accompanied 
by  paresis,  tremors,  and  convulsions.  Knoblauch  affirms  that  not  infre- 
quently the  loss  of  power  in  the  hind  legs  precedes  sleep,  and  that  weak- 
ness and  ataxia  are  prominent  symptoms  after  large  doses.  The  convul- 
sions, which  are  said  to  be  epileptic,  are  produced  by  very  large  toxic 
doses  only. 

Our  knowledge  of  the  physiological  action  of  sulphonal  is  very  imper- 
fect. Its  dominant  influence  is  upon  the  cerebral  cortex.  According  to 
Kast,  the  blood-pressure  is  not  altered  by  doses  which  produce  sleep,  and 
the  rise  of  arterial  pressure  noticed  by  Shick  in  non-curarized  animals 
may  have  been  produced  by  failure  of  respiration.  It  probably  depresses 
the  motor  spinal  cord,  although  this  has  not  been  proved,  and  Shick 
states  that  in  some  of  his  experiments  the  reflex  activity  was  increased, 
and  that  the  decline  of  the  reflexes  is  in  fact  due  to  stimulation  of 
Setschenow's  centre.  According  to  Shick,  it  has  no  influence  upon  the 
motor  or  sensory  nerves,  nor  upon  the  muscles. 

Kast  found  that  there  is  neither  microscopic  nor  spectroscopic  blood 
changes  in  animals  acutely  poisoned  by  the  drug.  The  drift  of  the  pres- 
ent evidence  indicates  that  sulphonal  has  no  distinct  effect  upon  tissue 
change,  but  the  matter  is  sub  judice.  * 

THERAPEUTIC  USE. — Sulphonal  is  a  valuable  hypnotic,  having,  how- 
ever, little  or  no  analgesic  effects,  and  being  extremely  slow  in  its  action 
and  scarcely  as  certain  and  satisfactory  as  is  trional.  Sleep  usually 
develops  in  from  a  half  to  one  hour  after  the  dose,  in  most  cases  gradually, 
but  sometimes  with  abruptness.  It  is  usually  quiet,  and  not  followed 
by  any  disagreeable  after-effects,  although  sometimes  mental  confusion 
and  lassitude  remain  during  the  following  day  ;  these  after-results  being, 
in  our  experience,  especially  apt  to  occur  in  cases  in  which  there  is  a 
distinct  depression  of  the  brain-nutrition.  Where  the  sleeplessness  is 
due  to  pain,  sulphonal  is  usually  not  serviceable  ;  but  in  the  insomnia  of 
insanity  it  often  acts  well.  Later  experience,  however,  does  not  seem  to 
carry  out  the  original  assertion  of  Kast,  that  sulphonal  is  especially  useful 
in  cases  of  insomnia  from  cardiac  diseases.  In  such  affections  it  appears 
to  be  not  only  an  uncertain,  but  even  a  dangerous  drug,  inferior  to 
chloral,  f  At  present  this  disagreeable  action  of  the  drug  does  not  seem 

*The  most  important  papers  are  those  of  Gritzka  (Inaug.  Dis.,  Berlin,  1891),  W.  J. 
Smith  (London  Pract.,  1889  and  1892),  and  Martin  Hahn  (Virchow's  Archiv,  cxxv.). 
John  Gordon  ( British  Med.  Journ.,  1893,  i. )  has  found  that  in  weak  solution  sulphonal  and 
urethan  retard  slightly  the  action  of  pancreatin  solution  upon  starch,  strong  solutions  of  the 
drug  having  no  effect ;  that  chloralamid,  antifebrin,  and  antipyrin  are  without  such  power ; 
but  that  paraldehyde,  whether  in  weak  or  strong  solution,  has  a  very  profound  effect, 
f  See  Joachiam  (  Therap.  Monalsh.,  iii.) ;  also  Schmey  (Ibid.,  1888,  ii.). 


SOMNIFACIENTS.  157 

to  be  explainable  by  any  influence  exerted  upon  the  heart.     It  is  possible 
that  it  is  due  to  irritation  of  already  congested  kidneys. 

The  action  of  sulphonal  upon  the  reflexes  would  indicate  its  employ- 
ment in  spasmodic  diseases,  and  it  has  been  used  with  asserted  good 
results  in  epilepsy,  hiccough,  chorea,  and  nocturnal  cramps ;  according 
to  E.  Andrews,7  it  is  very  effective  against  the  spasm  of  fractures.  It 
has  also  been  commended  as  a  sexual  sedative  in  chordee  and  spermator- 
rhoea. In  our  own  practice,  sulphonal  given  an  hour  after  meals  has 
seemed  to  have  value  as  an  intestinal  antiseptic.  It  is  asserted  that  it 
is  a  very  useful  remedy  in  colliquative  night-sweats. 

TOXICOLOGY. — Occasionally  even  the  single  dose  of  sulphonal  pro- 
duces nausea  (even  severe  gastric  pain  :  Dauthville8),  languor,  headache, 
depression,  or  pronounced  mental  disturbance.  In  rare  cases  sulphonal 
causes  excitement. 

Although  prodromic  symptoms  probably  always  usher  in  chronic  sul- 
phonal-poisoning ,  they  are  so  slight  and  so  lacking  in  anything  charac- 
teristic that  in  a  large  majority  of  cases  the  condition  appears  to  develop 
abruptly,  and  usually,  notwithstanding  the  suspension  of  the  remedy,  con- 
tinues to  the  fatal  issue,  death  occurring  in  about  seventy-five  per  cent. 
of  the  cases.  The  first  manifestations  are  increasing  lassitude  and  weak- 
ness, nausea,  and  gastro-intestinal  disturbance  as  shown  by  diarrhoea  or 
constipation.  Ordinarily  the  first  symptom  noted  is  the  pink  coloration  of 
the  urine,  which  deepens  until  the  fluid  becomes  of  a  dark  red  color,  stain- 
ing the  linen  upon  which  it  falls.  Usually  this  coloration  of  the  urine  is 
soon  followed  by  obstinate  constipation,  violent  vomiting,  spasm  of  the 
abdominal  muscles,  and  tenderness  upon  pressure  in  the  region  of  the 
liver  and  stomach.  At  the  same  time  there  develop  irregularity  of  gait, 
ataxia,  suppression  of  perspiration,  paresis  of  the  upper  extremities  or  per- 
chance paresis  of  irregular  groups  of  muscles,  pronounced  weakness  of  the 
legs,  loss  of  the  patellar  and  other  reflexes,  parsesthesia,  muscular  spasms, 
and  finally  a  condition  of  profound  collapse,  with  albuminous,  hemor- 
rhagic,  or  suppressed  urine,  ending  in  death.  After  death,  wide-spread 
fatty  degeneration,  involving  in  some  cases  the  heart,  but  especially  affect- 
ing the  liver  and  kidney,  has  been  found. 

In  some  cases  the  renal  changes  have  been  confined  to  a  glomerular 
or  cortical  nephritis,*  with  or  without  hemorrhage  ;  in  other  instances  the 
destruction  of  the  kidney  has  been  more  complete.  Probably  the  most 
characteristic  symptom  is  the  appearance  of  haematoporphyrin  in  the 
urine  ;  its  recognition  is  best  made  with  the  spectroscope. 

It  has  been  shown  by  Salkowski  (confirmed  by  Kast9),  that  ethyl-sulphonic 
acid  is  not  poisonous,  and  haematoporphyrin  appears  also  to  be  free  from  toxic 
properties  ;  so  that  the  symptoms  of  chronic  poisoning  are  probably  due  to  an 

*  A.  E.  Taylor  and  Joseph  Sailer  ( Contributions  William  Pepper  Lab.,  Philadelphia, 
1900,  cxx.)  found  that  the  degenerated  cells  of  the  liver,  spleen,  lymphatics,  and  kidney 
were  loaded  with  green  pigment,  whilst  the  blood-serum  contained  haematoporphyrin. 


158  GENERAL  REMEDIES. 

accumulation  of  sulphonal  in  the  system,  and  are  of  largely  primary  and  not  of  sec- 
ondary character,  though  some  of  them  may  be  in  fact  uraemic.  The  explanation 
of  the  occurrence  of  haematoporphyrinuria  is  at  present  very  difficult ;  *  frequently 
it  does  not  come  on  until  several  days  after  the  ingestion  of  the  last  dose.  In  a  fatal 
case  of  acute  poisoning  reported  by  Hoppe-Seyler  and  Ritter  it  was  not  present. 
As  has  been  demonstrated  by  Garrod  and  Hopkins,10  the  urine  of  patients  taking 
sulphonal  does  not  ordinarily  contain  more  haematoporphyrin  than  is  often  seen  in 
health.  It  is  generally  thought  that  the  haematoporphyrin  is  a  decomposition  product 
of  haematin,  and  Stokvis  u  believes  that  the  haematoporphyrinuria  is  due  to  the  absorp- 
tion of  altered  blood  from  hemorrhages  which  have  been  produced  in  the  mucous 
membrane  of  the  stomach  and  intestines  by  sulphonal, — an  explanation  which  is 
rejected  by  Kast  and  Weiss,12  and  also  by  Garrod  and  Hopkins,  for  apparently 
sufficient  reasons.  The  observation  of  Garrod  and  Hopkins,  that  the  increase 
of  urinary  haematoporphyrin  is  not  accompanied  by  a  corresponding  increase  in  the 
excretion  of  iron,  and  the  fact  that  in  the  cases  recorded  by  Percy  Smith  there  was 
no  lessening  in  the  number  of  the  red  blood-corpuscles  nor  of  the  haemoglobin,  lend 
probability  to  the  assertion  of  Quincke  (confirmed  by  Herting13),  that  the  coloring- 
matter  of  the  urine  is  not  in  reality  haematoporphyrin,  differing  from  it  in  its  spectro- 
scopic  lines.  Franz  Miiller,  however,  found  in  a  case  of  sulphonal-poisoning  which 
recovered  that  the  haemoglobin  fell  during  the  period  of  red  urine  to  forty-five  per 
cent. ,  returning  afterwards  to  eighty-five  per  cent. ;  whilst  Hoppe-Seyler  believes  that 
the  anatomical  changes  in  sulphonal-poisoning  are  really  secondary  to  the  destruction 
of  the  red  blood-disks. 

The  exanthem  of  sulphonal-poisoning  may  be  bullatous,  but  is  usually 
a  minutely  papulous  eruption,  which  has  been  described  by  some  as 
resembling  that  of  measles,  by  others  as  like  that  of  scarlet  fever.  It  is 
not  rarely  symmetrical,  and  often  shows  a  disposition  to  follow  the  nerve- 
trunks,  so  that  it  is  probably  neurotic, — a  conclusion  which  is  strongly  con- 
firmed by  the  fact  that  unmistakable  multiple  neuritis  has  been  reported 
as  caused  by  the  continued  use  of  sulphonal  (W.  Erbsloh15). 

In  the  treatment  of  sulphonal-poisoning  the  first  attention  should  be 
given  to  seeing  that  the  bowels  are  well  opened,  which  usually  requires 
very  energetic  measures.  The  use  of  the  alkaline  carbonates,  as  sug- 
gested by  Miiller,14  probably  offers  the  best  hope  of  any  therapeutic 
measures,  f  Large  amounts  of  water,  which  may  carry  the  alkali,  should 
be  introduced  both  by  the  mouth  and  by  hypodermoclysis,  to  wash  the 
poison  out  of  the  system. 

ADMINISTRATION. — The  dose  of  sulphonal  is  from  ten  to  forty -five 
grains  (0.7-3  Gm. ).  It  is  absorbed  with  difficulty,  and  should  always 
be  administered  in  fine  powder  diffused  in  water  or  milk,  or  enclosed  in 
capsules.  We  have  seen  compressed  pills  of  sulphonal  pass  through  the 
body  unchanged,  and  have  no  doubt  that  the  reported  great  slowness  or 
even  failure  of  action  has  often  depended  on  improper  methods  of  admin- 
istration. It  should  be  an  invariable  rule  when  sulphonal  is  given 

*  In  an  elaborate  research  upon  rabbits,  Neubauer  (A.  E.  P.  P.,  1900,  Bd.  xliii.) 
attempted  unsuccessfully  to  determine  how  the  haematoporphyrin  is  produced  by  sul- 
phonal. In  agreement  with  Kast  and  Weiss,  he  was  unable  to  produce  haematoporphyrin. 
by  digesting  the  normal  organs  of  the  rabbit  with  sulphonal. 

f  Alkaline  waters,  however,  in  Pollitz's  case  (  Vierteljahr.f.  Gerichtl.  Med.,  1898,  v.} 
apparently  failed  to  do  any  good. 


SOMNIFACIENTS.  159 

continuously  every  two  weeks  to  suspend  its  employment  for  some  days, 
so  as  to  allow  the  system  to  clear  itself ;  and  the  urine  should  also  always 
be  carefully  watched  and  the  first  appearance  of  the  red  tint  be  the  signal 
for  immediate  withdrawal. 

SULPHONETHYLMETHANUM.     U.  S. 

Trional  {diethylsulphonmethylethylmethane)  occurs  in  commerce  as  a 
colorless,  shining,  bitter  crystalline  powder,  soluble  in  three  hundred  and 
twenty  parts  of  cold,  easily  soluble  in  hot  water  ;  also  in  alcohol  and 
ether.  Tetronal  (diethylsulphondiethylmethane),  although  affirmed  by 
Baumann  and  Kast  to  be  more  powerful  as  an  hypnotic  than  trional,  has 
failed  to  come  into  practical  use  as  an  hypnotic. 

Locally  trional  seems  to  be  inert.  It  is  absorbed  much  more  rapidly 
than  is  sulphonal  and  acts  much  more  promptly.  Concerning  its  elimi- 
nation we  have  no  information.  Given  to  man  in  doses  of  from  fifteen  to 
twenty  grains,  it  usually  causes  in  from  fifteen  minutes  to  an  hour  a  quiet, 
apparently  normal,  sleep. 

There  appears  to  be  no  recorded  case  of  fatal  acute  poisoning  by  trional. 
Sixty  grains  are  said  to  have  produced  haematoporphyrinuria  (Berger1), 
but  one  hundred  and  twenty  grains  have  been  recovered  from  without  very 
serious  symptoms  (Collatz 2).  One  hundred  and  twenty  grains  (Wightwick 
and  Rolleston s)  caused  dilated  pupils,  profound  muscular  relaxation,  loss  of 
reflexes,  and  pronounced  cardiac  depression,  without  haematoporphyrinuria. 
Although  trional  is  less  apt  than  is  sulphonal  to  cause  chronic  poisoning,  a 
number  of  cases  have  occurred.  The  symptoms  have  been  great  lassitude, 
giddiness,  headache,  tinnitus  aurium,  gastro-intestinal  pain,  vomiting,  ob- 
stinate constipation,  pronounced  tremors,  ataxia,  especially  shown  by  an 
uncertain  gait,  and  in  one  or  two  cases  even  a  pronounced  general  paresis, 
with  loss  of  control  over  the  sphincter  ;  also  lessened  secretion  of  the 
urine,  and  haematoporphyrinuria.  Strangury  has  been  noted,  whilst  even 
the  therapeutic  dose  may  cause  excessive  acidity  of  the  urine.  These 
symptoms  differ  from  those  produced  by  sulphonal  chiefly  in  that  the 
haematoporphyrinuria  is  less  pronounced,  and  in  that  the  premonitory 
symptoms  are  more  marked.  As  Hart  has  reported  double  wrist-  and 
foot-drop,  with  diminished  reflexes  and  loss  of  motor  power,  it  is  probable 
that  trional  may  produce  a  peripheral  neuritis. 

In  acute  trional-poisoning  the  stomach  should  be  evacuated  ;  very 
dilute  solution  of  sodium  carbonate  should  be  given  freely  by  the  mouth 
and  by  hypodermoclysis  ;  strychnine  and  cardiac  stimulants  used  hypo- 
dermically  pro  re  nata.  In  chronic  poisoning  the  most  important  part  of 
the  treatment  is  the  free  administration  in  every  possible  way  of  a  one  per 
cent,  solution  of  sodium  carbonate.* 

Beyond  the  fact  that  the  dominant  influence  of  trional  is  upon  the  cere- 

*  For  cases  of  poisoning,  see  Vogel  (Berl.  Klin.  Woch,  1899,  875) ;  also  Munch.  Med. 
Woch.,  xiii.  928;  Coleman,  Med.  News,  1900,  Ixxvii.  129;  jChurch,  American  Med.,  1901, 
ii.  729 ;  Hart,  American  Journ.  Med.  Set,  1901,  cxxi. 


160  GENERAL  REMEDIES. 

brum,  we  have  little  definite  knowledge  as  to  the  way  in  which  it  acts. 
According  to  Haenel,4  the  rate  of  the  mental  function  is  distinctly  les- 
sened by  it,  and  continues  slow  for  some  time  after  the  sleep  period.  If 
it  be  true,  as  asserted  by  Egasse,5  that  in  animals  trional  sleep  is  at- 
tended by  increase  in  the  activity  of  the  reflexes,  it  probably  stimulates 
the  spinal  cord.  Kronfeld,6  as  the  result  of  sphygmomanometrical 
studies,  affirms  that  the  blood-pressure  is  always  lowered  during  sleep 
caused  by  trional,  the  fall  being  due,  in  his  belief,  to  depression  of  the 
vaso-motor  centres. 

Trional  may  be  given  in  hot  water  or  hot  milk  or  in  capsules.  Dose, 
ten  to  thirty  grains  (0.66  to  2  Gm. ). 

PARALDEHYDUM. — PARALDEHYDE,  U.  S.,  which  was  first  brought  to 
the  notice  of  the  profession  by  Cervello,  is  a  colorless  liquid,  having  a 
boiling  point  of  123.5°  C. ,  and  an  extremely  disagreeable  odor  and  taste. 

Local  Action. — Paraldehyde  is  locally  irritant,  and  is  likely,  when 
taken  in  large  doses,  to  disturb  the  stomach,  or  at  least  to  give  rise  to 
disagreeable  eructations. 

Absorption  and  Elimination. — Absorption  of  paraldehyde  commences 
at  once,  and  its  action  is  usually  manifested  in  a  few  minutes.  Its  elimi- 
nation begins  promptly,  but  is  carried  on  slowly,  so  that  the  breath  fre- 
quently reeks  of  it  for  hours  after  the  patient  has  awakened.  Its  chief 
channel  of  escape  is  probably  through  the  respiratory  organs,  but  it  has 
been  found  in  the  urine  by  Gordon  and  Raimann,  and  Raimann  also 
believes  that  it  escapes  to  some  extent  with  the  perspiration.  It  appears 
not  to  be  destroyed  in  the  system. 

PHYSIOLOGICAL  ACTION. — According  to  the  physiological  studies  of 
Cervello,  PreVost,  and  Gordon,  the  injection  of  from  one-half  to  one  drachm 
of  paraldehyde  produces  in  the  rabbit  and  dog  loss  of  sensibility,  and  in  a 
very  short  time  deep  sleep  with  general  muscular  relaxation,  some  slow- 
ing of  the  breathing  and  of  the  rapidity  of  the  heart,  without,  however, 
distinct  lowering  of  the  blood-pressure.  After  very  large  doses  reflex 
excitability  is  abolished,  and  death  takes  place  through  respiratory  paral- 
ysis, the  cardiac  action  and  blood-pressure  long  resisting  the  action  of 
the  drug.  In  man  paraldehyde  produces  a  deep  sleep,  with,  if  the  dose 
have  been  large  enough,  loss  of  reflex  activity,  some  slowing  of  the  respi- 
ration and  pulse-rate,  and  slight  fall  in  the  temperature.  The  symptoms 
usually  pass  off  without  disagreeable  after-effects,  but  after  very  large 
doses  there  are  sometimes  malaise,  headache,  giddiness,  nausea,  or  even 
vomiting.  Usually  there  is  some  diuretic  action. 

Nervous  System. — Paraldehyde*  probably  produces  sleep  by  a  direct 
action  upon  the  cerebral  cells.  Bokai  and  Barcsi  *  have  found  that  there 
is  marked  relaxation  of  the  cerebral  blood-vessels,  but  this  is  probably  the 

*  Cappelli  and  Brugia  *  have  also  noted  lessening  in  the  size  of  the  brain,  under  the  in- 
fluence of  paraldehyde,  in  a  man  suffering  from  defect  of  the  skull. 


SOMNIFACIENTS.  161 

result,  not  the  cause,  of  the  arrest  of  brain  function.  The  characteristic 
effect  of  the  drug  upon  muscular  action  is  depression,  which  is  probably 
of  spinal  origin,  though  this  has  not  been  absolutely  proved.  Bokai  and 
Barcsi  affirm  that  after  small  doses  there  is  a  period  of  heightened  re- 
flexes. 

Circulation. — Upon  the  circulation  paraldehyde  has  very  little  influ- 
ence, nor  is  the  blood  itself  affected  except  by  the  very  largest  doses. 
According  to  Henoque,  intravenous  injections  of  paraldehyde  in  the 
animal  are  followed  by  disappearance  of  the  absorption-band  in  the  yellow- 
green  of  the  spectrum  oxyhaemoglobin. 

Nutrition. — According  to  Dockendorff,  the  elimination  of  nitrogen  and 
phosphorus  is  somewhat  lessened  by  paraldehyde,  and  in  cases  of  chronic 
poisoning  in  man  the  elimination  of  phosphates  has  been  found  to  be  very 
low.  Heemoglobinuria  has  been  noticed  in  the  horse,  but  not  in  other 
animals  poisoned  with  paraldehyde. 

TOXICOLOGY. — Very  large  doses  of  paraldehyde  have  been  taken  with- 
out fatal  results,  although  death  is  alleged  to  have  been  produced  by  four 
ounces  (Drage5).  In  one  case  reported  by  Raimann,*  nearly  eight  hun- 
dred grains  produced  simply  deep  sleep  lasting  nineteen  hours,  without 
evil  result.  Probst 5  reports  one  case  in  which  nine  hundred  grains  gave 
sleep  lasting  twenty-two  hours,  without  serious  symptoms  ;  and  another 
in  which  nearly  five  ounces  of  paraldehyde,  taken  within  thirty-six 
hours,  produced  profound  coma,  marked  lividity,  excessive  muscular 
relaxation  and  vomiting,  slight  fall  of  temperature,  without  pronounced 
depression  either  of  the  heart's  action  or  of  the  blood-pressure,  and  without 
complete  loss  of  the  reflexes.  The  urine  at  first  was  in  no  way  abnormal ; 
later  it  contained  acetone.  On  the  second  day  mental  aberration  appeared 
and  continued,  and  on  the  fifth  day  distinct  tremors  appeared  :  by  the 
seventh  day  the  case  was  convalescent.  Although  chronic  poisoning  has 
frequently  been  produced  by  paraldehyde,  we  know  of  no  recorded  fatal 
case.  Disturbances  of  the  digestion  are  common.  More  characteristic  is 
a  psychic  disturbance  somewhat  resembling  delirium  tremens  and  in 
many  cases  associated  with  tremors  and  muscular  weakness.  These 
symptoms  usually  subside  with  the  cessation  of  the  taking  of  the  drug. 
In  one  case6  thirty-five  grammes  were  taken  daily  for  a  year.  In  a  second 
case 7  five  grammes  were  taken  daily  for  thirteen  years,  without  the  pro- 
duction of  any  symptoms.  In  the  experiments  of  Bokai  and  Barcsi  it 
was  found  possible  to  produce  in  the  animal,  by  the  continued  use  of  paral- 
dehyde, fatty  degeneration  of  the  liver  and  of  the  heart-muscle,  but  no 
such  result  has  been  noted  in  man.  In  some  cases  nasal  ulcers,  skin 
eruptions,  and  various  vaso-motor  disturbances  are  said  to  have  been 
produced  by  the  long  administration  of  the  drug. 

Paraldehyde  is  a  very  useful  hypnotic  in  the  numerous  cases  of  mild 
insomnia,  such  as  is  seen  in  neurasthenia,  and  is  also  used  as  an  adjuvant 
to  other  remedies  in  delirium  tremens,  insanity,  and  the  more  serious 
forms  of  morbid  wakefulness  not  dependent  upon  pain. 

ii 


162  GENERAL  REMEDIES. 

ADMINISTRATION. — The  dose  of  paraldehyde  is  from  one-half  to  two 
drachms.  Its  unpleasant  taste  may  be  partially  hidden  by  the  use  of  the 
aromatic  oils. 

MINOR  HYPNOTICS. 

Chloretone,  Acetonchloroform,  or  Trichlor  Tertiary  Butyl  Alcohol,  is  a  white 
crystalline  compound  with  a  camphoraceous  odor  ;  very  soluble  in  strong  alcohol 
and  ether,  soluble  to  the  extent  of  about  one  per  cent,  in  cold,  more  soluble  in 
boiling,  water.* 

PHYSIOLOGICAL  ACTION. — In  proper  dose  chloretone  causes  in  the  lower  ani- 
mals a  profound  sleep,  with  complete  and  prolonged  anaesthesia,  without  marked 
effect  upon  the  respiration  or  blood-pressure.  This  condition  may  be  continued  as 
long  as  four  days,  and  the  animal  wake  unharmed  ;  but  if  the  dose  has  been  suffi- 
cient, after  several  days  of  sleep  death  occurs  from  asphyxia.  According  to  E.  M. 
Houghton  and  T.  B.  Aldrich,1  applied  locally  to  the  frog's  heart,  it  slows  the  rate 
and  produces  a  more  complete  systole,  and  has  no  action  upon  the  blood  itself. 
Locally  applied  it  is  a  sensory  nerve  paralyzant.  Houghton  and  Aldrich  having 
failed  to  detect  it,  acetone,  or  chloroform  in  any  of  the  excretions  of  the  poisoned 
animal,  believe  that  it  undergoes  decomposition  in  the  body. 

THERAPEUTICS. — Chloretone  has  been  used  to  a  considerable  extent  in  practical 
medicine,  but  appears  not  to  have  fulfilled  the  expectations  of  the  profession,  and  is 
not  employed  as  much  as  formerly.  Its  local  irritant  effect  greatly  interferes  with 
its  use  as  an  anaesthetic,  but  its  one  per  cent,  solution  is  distinctly  antiseptic  and 
sometimes  acts  well  upon  foul,  irritable  ulcers  and  wounds.  It  has  also  been  em- 
ployed in  doses  of  from  five  to  eight  grains  in  vomiting,  gastric  cancer,  and  other 
painful  local  conditions  of  the  stomach.  As  an  hypnotic  it  has  been  used  in  ordinary 
insomnia,  delirium  tremens,  and  various  forms  of  insanity,  but  is  uncertain  in  its 
action.  According  to  Wharton  Sinkler,2  it  is  useful  in  epilepsy,  and  especially  in 
petit  mal,  in  doses  of  from  three  to  five  grains,  three  times  a  day. 

We  know  of  no  deaths  reported  from  chloretone  ;  one  hundred  and  twenty  grains 
taken  during  twenty-four  hours  (W.  M.  Donald3)  caused  profound  sleep  lasting  for 
six  days,  without  any  untoward  symptoms  except  gastric  irritability.  The  pulse 
ranged  from  85  to  104,  and  the  bodily  temperature  fell  to  96°  F.  During  the  latter 
part  of  the  sleep  the  patient  could  be  aroused  for  brief  conversation,  t 

The  dose  of  chloretone  has  been  set  down  from  twelve  to  fifteen  grains  (0.8-1 
Gm.),  but  we  have  exhibited  thirty  grains  in  the  twelve  hours  without  the  produc- 
tion of  any  symptoms  whatever  ;  and  Wade,4  who  has  used  the  drug  largely,  gave 
the  average  dose  as  from  thirty-five  to  fifty  grains. 

Laboratory  Use.  —Chloretone  is  highly  commended  by  some  physiologists  for 
use  in  the  laboratory,  but  we  have  found  the  difficulty  of  administration,  growing 
out  of  its  insolubility,  to  interfere  seriously  with  its  practical  employment.  When 
recovery  from  the  anaesthetic  sleep  is  desired,  0.2  Gm.  per  kilo  body-weight  may 
be  given  ;  but  when,  as  in  class  demonstration,  it  is  intended  to  put  the  animal  to 
death,  much  larger  doses  may  be  administered  in  many  cases  without  interfering 
with  the  experiment. 

*  Chloretone  was  discovered  by  Willgerodt  in  1881,  and  suggested  as  a  substitute  for 
chloral  by  him  in  1884.  In  1891  John  J.  Abel  began  to  experiment  with  it,  and  in  1894 
demonstrated  its  usefulness  as  a  practical  hypnotic  and  anaesthetic  for  the  physiologist 
(see  Science,  January,  1895). 

Abel  states  that  Faust  has  found  that  urethan  and  chloretone  rubbed  together  make 
a  fluid.  The  physiological  properties  of  this  substance  do  not  seem  to  have  been  investi- 
gated. 

t  According  to  Impens  (A.  I.  P.  T.,  1901,  viii.  77),  chloretone  is  a  much  more  danger- 
ous hypnotic  than  chloral,  the  ratio  of  the  somnifacient  to  the  fatal  dose  being  only  as 
1:1.7. 


SOMNIFACIENTS.  163 

CARBAMAS.  U.  S.  Ethyl  Carbamate.  Urethane.  Carbamic  Ether. — 
This  ester  of  carbamic  acid  occurs  in  the  form  of  odorless  columnar  crystals  or 
scales,  of  a  cooling,  saline  taste,  soluble  in  less  than  one  part  of  water.  It  was 
originally  proposed  by  Schmiedeberg 12  as  an  hypnotic  which  acts  directly  upon  the 
cerebral  cortex,  depresses  the  motor  side  of  the  spinal  cord,  but  has  very  little 
influence  upon  the  circulation,  the  arterial  pressure  remaining  normal  even  during 
deep  narcosis.  Clinical  experience  has  shown  that  urethane  is  somewhat  uncertain 
in  its  action,  but  that  it  may  be  used,  sometimes  with  satisfactory  results,  as  an  hyp- 
notic and  also  as  an  anti-convulsant  in  puerperal  and  other  serious  eclampsia  as 
well  as  in  tetanus.  The  official  dose  of  it  is  fifteen  grains  (i  Gm.),  but  seventy- 
five  grains  have  been  taken  without  very  distinct  effects,  and  twice  the  official  dose 
may  be  given  without  danger. 

AMYLENE  HYDRATE,  a  clear,  colorless  liquid,  of  a  penetrating  odor,  soluble 
in  eight  parts  of  water,  was  brought  forward  in  1885  by  Von  Mering  and  Thier- 
felder,13  and  is  said  by  its  discoverers  to  act  very  much  like  chloral,  but  to  require 
double  the  dose.  Five  grammes  of  amylene  hydrate  inhaled  by  a  man  produced 
profound  narcosis,  paralysis  of  the  extremities,  dilated  pupil,  abolished  reflexes ; 
slow,  deep,  irregular  respiration  ;  failing  pulse,  with  depression  of  the  temperature. 
The  drug  appears  to  differ  from  most  other  hypnotics  in  being  a  poison  both  to  the 
voluntary  and  cardiac  muscles.  The  assigned  dose  is  from  thirty  to  forty  minims 
(2-2.5  C.c.). 

AMYLENE  CHLORAL.  Dormiol. — This  drug,  formed  by  the  union  of  chloral 
and  amylene  hydrate,  is  a  colorless,  oily  liquid  with  a  camphor-like  odor,  insoluble 
in  water.  There  is  much  recorded  clinical  evidence  as  to  its  value  in  insomnia 
which  is  not  dependent  upon  the  existence  of  pain.  It  has  been  largely  employed 
in  insane  asylums,  and  it  is  asserted  that  it  has  no  disagreeable  after-effects  ;  that 
it  is  not  depressant  to  the  heart,  and  may  be  used  in  cardiac  insomnia ;  and  that 
when  continuously  exhibited  it  does  not  produce  chronic  poisoning.  Its  action  is 
prompt,  but  somewhat  fugacious,  and  patients  rapidly  become  accustomed  to  its 
use.  Dose,  from  ten  grains  to  one  drachm  (1-4  Gm.)  in  capsules  or  dropped  in 
cold  water. 

METHYLAL,  brought  forward  by  Personali,  is  said  by  Motrokhin,  when  inhaled 
by  man  in  doses  of  two  ounces,  to  produce  sleep  with  loss  of  sensibility,  without 
any  effect  upon  the  heart.  Popoff,  however,  affirms  that  it  acts  directly  upon  the 
cardiac  muscle.  It  is  so  rapidly  absorbed  and  eliminated  that  it  should  probably 
be  considered  an  anaesthetic  rather  than  an  hypnotic,  and  it  is  said  that  it  very 
rapidly  loses  its  power  over  patients.  Dose,  from  one  to  two  drachms  (4-8  Gm.). 

HEDONAL  (Methyl-propyl-carbinol-urethane}. — This  occurs  in  colorless  crystals, 
sparingly  soluble  in  cold  water,  of  a  disagreeable  somewhat  menthol-like  taste, 
which  are  believed  to  split  up  in  the  system  into  carbon  dioxide,  ammonia,  and 
urea.  It  has  been  brought  forward  as  an  hypnotic,  which  in  severe  cases  of  insom- 
nia or  when  the  patient  is  kept  awake  by  pain,  is  of  little  service,  but  is  valuable  in 
mild  cases  on  account  of  having  no  disagreeable  after-effects.  No  cases  of  poisoning 
by  it  have  been  reported,  and  so  far  its  prolonged  use  has  not  been  followed  by 
disagreeable  symptoms.  It  is  not  known  to  have  any  influence  upon  the  circulation, 
and,  resembling  trional  in  its  action,  has  been  especially  commended  as  an  alterna- 
tive to  that  drug.  Probably  owing  to  the  formation  of  urea,  it  sometimes  acts  as  a 
diuretic,  and,  according  to  de  Moor,  this  action  is  much  increased  by  its  adminis- 
tration in  solution.  Dose,  from  fifteen  to  forty-five  grains  (1-3  Gm.),  preferably 
administered  in  capsules  half  an  hour  before  the  desired  effect. 

ISOPRAL  (  Trichlorisopropylalkohol). — This  substance,  which  has  been  proposed 
as  an  hypnotic,  occurs  in  microscopic  prisms,  melting  at  49°  C. ,  readily  soluble  in 


164  GENERAL  REMEDIES. 

water,  alcohol,  or  ether,  readily  subliming,  and  having  a  camphor-like  odor  and 
aromatic  taste.  According  to  Impens,1*  it  is  readily  absorbed  through  the  skin,  the 
subcutaneous  tissue,  and  the  digestive  tract,  its  effects  when  taken  internally  being 
manifested  in  from  three  to  five  minutes.  It  is  said  also  that  a  stream  of  air  directed 
over  warmed  isopral  will  produce  marked  narcosis  in  the  lower  animals  in  ten  or 
twelve  minutes.  It  is  eliminated  through  the  kidneys  chiefly  as  a  glycuronic  acid 
compound,  trichlorisopropylglycuronic  acid,  although  it  is  believed  also  to  escape 
to  some  extent  through  the  respiratory  tract.  According  to  Impens,  in  proportion 
to  its  narcotic  influence  it  is  only  half  as  poisonous  to  the  lower  animals  as  is  choral. 
The  dose  for  man  does  not  seem  to  have  been  determined.  In  the  dog  the  smallest 
dose  certain  to  produce  sleep  is  said  to  be  0.093  gramme  per  kilogramme,  0.6 
gramme  being  the  lethal  dose. 

YERONAL  (Di-ethyl-malonyl-nrea). — This  drug  occurs  in  odorless,  colorless, 
slightly  bitter  crystals,  soluble  in  one  hundred  and  forty-five  parts  of  water  at  68°  F. 

Originally  brought  forward  by  E.  Fischer  and  J.  von  Mering15  as  an  hypnotic, 
veronal  has  been  tested  by  various  clinicians  in  all  forms  of  insomnia,  with  reports 
which  are  very  favorable.  It  has  been  found  by  Mendel  and  Kron  and  by  Weber* 
to  be  especially  valuable  in  the  treatment  of  insomnia  with  motor  excitement  or 
active  hallucinations,  also  in  depressive  insanity  ;  contrary  to  the  statements  of  some 
clinicians,  Mendel  and  Kron  deny  its  value  as  an  antineuralgic.  Concerning  its 
general  physiological  action  we  have  little  knowledge,  but  C.  Trautmann 16  affirms 
as  the  result  of  experimental  studies  that  it  lessens  nitrogenous  elimination.  Various 
authorities  assert  that  it  leaves  no  after-effects ;  but  Jolly,  Rosenfeld,  and  Wiirth 
have  noticed  after  its  taking,  malaise,  headache  and  giddiness,  and  even  disturb- 
ances of  speech,  chiefly  when  it  has  been  given  in  very  large  doses. 

Originally  recommended  in  doses  of  half  a  gramme,  veronal  has  been  given  prac- 
tically up  to  one  and  a  half  grammes,  but  has  been  reported  by  various  observers 
as  efficient  in  much  less  amount ;  so  that  at  present  from  ten  to  fifteen  grains  (0.6-1 
Gm. )  may  be  considered  as  its  dose.f 

HYPNONE  or  ACETOPHENONE,  originally  suggested  by  Dujardin-Beaumetz, 
according  to  various  authorities,  acts  more  powerfully  as  a  paralyzant  than  as  an 
hypnotic,  and  has  been  condemned  by  a  large  number  of  clinicians.  The  maximum 
dose  given  by  Rey,  without,  however,  the  production  of  sleep,  was  sixty  drops,  or 
twenty-three  grains  (1.5  Gm. ). 

CHLORALFORMAMIDUM.  U.  S. — Under  the  names  of  chloralamid,  chloralform- 
amid,  a  compound  of  chloral  and  formamid  has  been  used  as  an  hypnotic  and 
has  been  made  official.  It  is  a  slightly  bitter  crystalline  substance,  soluble  in  twenty 
parts  of  water  and  one  and  a  half  parts  of  strong  alcohol.  It  is  decomposed  by  hot 
water,  but  its  solution  in  cold  water  is  moderately  permanent ;  it  is  rapidly  decom- 
posed by  alkalies.  In  the  lower  animals,  chloralamid  produces  lethargy,  narcosis, 
sleep,  and,  finally,  if  it  has  been  taken  in  sufficient  amount,  death  from  failure  of 
respiration.  According  to  Langgaard,5  in  the  rabbit  the  sleep  is  accompanied  by 
pronounced  decrease  in  the  amount  of  air  drawn  in  and  out  of  the  lungs  and  pro- 
nounced lessening  of  the  blood-pressure.  These  results,  however,  are  scarcely  in 
accordance  with  those  of  other  observers.  Otto  Halasz 8  found  the  blood-pressure 
very  slightly  affected.  Von  Mering  and  Zuntz  have  shown  that  the  fall  in  the  air 
movements  of  respiration  obtained  by  Langgaard  was  not  greater  than  that  which 
results  from  sleep,  and  also  obtained  deep  sleep  and  even  complete  anaesthesia  in 
the  rabbit  without  fall  of  the  arterial  pressure. 

*  For  references,  see  D.  W.  M.,  1903,  pp.  608,  726. 

f  See  S.  Jb.,  Bd.  cclxxviii.,  cclxxix,  for  abstracts  of  the  literature  to  date  ;  also  Ther. 
Caz.,  1903. 


SOMNIFACIENTS.  165 

In  a  series  of  experiments  made  by  David  Cerna  and  H.  C.  Wood  in  the  lab- 
oratory of  the  University,  it  was  found  that  the  influence  of  chloralamid  upon  the 
circulation  is  very  feeble,  only  the  largest  toxic  dose  lowering  the  arterial  pressure 
at  all.  In  the  dog  the  respirations  were  always  enormously  hurried  by  the  drug, 
although  no  experiments  were  made  to  determine  the  absolute  amount  of  air  moved. 
The  action  of  the  drug  upon  the  spinal  cord  was  also  very  feeble,  and  no  perceptible 
influence  was  shown  upon  the  nerves  and  muscles  ;  but  the  effect  upon  the  cerebral 
cortex  was  very  pronounced. 

THERAPEUTICS. — Chloralamid  is  a  rather  slowly  acting  and  uncertain  hypnotic, 
which  usually  does  not  cause  any  unpleasant  after-effects,  but  sometimes  produces 
confusion,  giddiness,  and  headache.  It  has  been  especially  recommended  by  Hage- 
mann  and  Hiifler7  for  the  relief  of  cardiac  asthma.  Our  knowledge  of  its  physio- 
logical action  seems  to  show  that  the  assertions  of  various  clinicians,  that  it  is  better 
borne  than  chloral  in  cases  where  there  is  cardiac  weakness,  have  a  foundation  in 
fact.  It  should  be  given  in  doses  of  from  thirty  to  fifty  grains  (1.9-3.2  Gm. ),  admin- 
istered in  watery  solutions  or  capsules  half  an  hour  before  the  expected  time  of  sleep. 

CHLORALOSE  occurs  in  small  crystals,  having  a  very  bitter  and  disagreeable 
but  not  acrid  taste.  It  is  freely  soluble  in  hot  water,  slightly  so  in  cold  water.  It 
was  first  brought  forward  as  a  remedial  agent  by  Hanriot  and  Richet,8  who  state 
that  five  grammes  of  it  will  produce  in  a  dog  of  ten  kilogrammes'  weight  symptoms  of 
intoxication  followed  by  a  most  profound  sleep  in  which  all  sensibility  is  lost,  although 
the  reflex  activities  are  greater  than  normal  ;  that  upon  the  circulation  it  has  but 
little  power,  the  arterial  pressure,  even  when  there  is  profound  unconsciousness, 
being  scarcely  affected  ;  that  during  the  unconsciousness  not  only  is  the  motor  side 
of  the  spinal  cord  more  active  than  normal,  but  the  cerebral  cortex  is  excessively 
excitable,  the  animals  experimented  upon  offering  a  strong  contrast  with  chloral- 
ized  dogs,  in  which  the  cerebral  cortex  is  almost  devoid  of  responding  power.  The 
statements  of  its  discoverers,  that,  taken  in  doses  of  five  grains,  it  would  produce 
in  man  a  profound  sleep  lasting  for  many  hours,  and  not  followed  by  unpleasant 
after-effects,  have  not  been  sustained.  Its  action  is  very  variable  ;  the  dose  of  ten 
grains  will  in  many  cases  produce  no  effect,  and  yet  in  other  cases  has  caused  com- 
plete unconsciousness  with  marked  cyanosis  and  slowing  of  the  pulse.  Its  thera- 
peutic influence  has  frequently  been  attended  by  very  unpleasant  symptoms,  such  as 
tremors,  partial  or  general  paralysis,  great  slowing  of  the  pulse  and  cardiac  depres- 
sion, involuntary  discharge  of  urine  during  sleep,  excessive  vomiting,  and  delirious 
intoxication.  In  our  experience,  although  occasionally  useful,  the  drug  has  not 
proved  generally  satisfactory.  Dose,  from  five  to  ten  grains  (0.3-0.65  Gm.).* 

BUTYL-CHLORAL  HYDRATE. — This  substance,  formed  by  the  action  of  chlorine 
gas  upon  aldehyde,  crystallizes  in  small,  glittering  tables,  is  soluble  with  difficulty  in 
water,  and  when  in  solution  breaks  up  in  the  presence  of  an  alkali  into  sodium 
chloride,  sodium  formate,  and  bichlorallylene.  Under  the  name  of  croton-chloral, 
it  was  introduced  into  practical  medicine  by  Oscar  Liebreich,9  because  he  found 
that,  whilst  acting  in  general  like  chloral,  it  depressed  less  powerfully  the  pulse  and 
respiration,  and  especially  affected  the  trigeminal  nerve,  lessening  its  sensibility 
before  the  appearance  of  narcosis,  a  drachm  of  it  producing  complete  anaesthesia  of 
the  head  and  eyeballs.  According  to  Liebreich,  toxic  doses  produce  deep  sleep, 
trigeminal  anaesthesia,  and  arrest  of  respiration,  the  circulation  being  maintained 
with  great  tenacity.  These  assertions  of  Liebreich  have  not,  however,  been  sus- 
tained. J.  von  Mering  found  that  the  cornea  remained  sensitive  until  respiration 
was  reduced  to  half  its  normal  rate ;  that  in  dogs,  cats,  and  rabbits  the  drug,  in 
small  or  in  large  dose,  lessened  the  blood-pressure,  and  when  brought  in  concen- 
trated form  in  contact  with  the  heart,  arrested  its  movements.  These  results  have 

*  See  Brit.  Med.  Journ.,  1893,  ii.  For  cases  of  unpleasant  action,  see  Schmidt's 
Jahrb.,  ccxlv. ;  also  Revue  Neurolog.,  1894,  ii. 


i66 


GENERAL  REMEDIES. 


been  confirmed  by  E.  Lahousse10  and  H.  Mindel  Schmidt,"  so  that  it  is  very  difficult 
to  perceive  wherein  the  action  of  croton-chloral  practically  differs  from  that  of  chloral. 
Croton-chloral  was  asserted  by  Liebreich  to  be  very  powerful  in  relieving  neu- 
ralgia, tic  douloureux,  and  other  painful  affections  of  the  trigeminus,  and  consider- 
able support  has  been  given  by  clinicians  to  his  statement.  On  the  whole,  however, 
the  drug  has  failed  to  sustain  itself,  and  is  at  present  but  little  used :  that  it  has 
any  greater  effect  than  chloral  is  very  doubtful.  It  is  usually  administered  in  doses 
of  from  five  to  twenty  grains  (0.32-1.3  Gm. ),  in  syrup.  The  safest  plan  is  to  give 
five  grains  every  half-hour  until  thirty  grains  have  been  taken  or  relief  afforded. 
Liebreich  uses  it  according  to  the  following  formula  :  butyl-chloral  hydrate,  five  to 
ten  parts  ;  glycerin,  twenty  parts  ;  distilled  water,  one  hundred  and  thirty  parts. 
Dose,  half  an  ounce,  followed  in  five  minutes  by  a  second,  and  ten  minutes  later  by 
a  third  unless  relief  is  afforded. 


REFERENCES. 


OPIUM. 

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also  U.  P.  M.  B.,  1903. 

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35.  OTT N.  Y.  M.  J..  1883. 

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39.  REICHERT  .  .  .   .  T.  G.,  Aug.,  1902. 


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OTT Medical  Bulletin,  1899,  xxi. 

410. 

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Ph.  Post,  1899,  743. 
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ELISCHER  ....  Hk.,  Feb.  1902. 
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CHLORAL. 

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FELTZ  and  RITTER  .  C.  R.  S.  B.,  Ixix.  966. 

ECHARD A.  E.  P.  P.,  xii.  276. 

BORNTRAEGER     .  In.  Dis.,  Marburg,  1879. 

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RICHARDSON     .  .  M.  T.  G.,  Sept.  4,  1870. 

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RAJEWSKY  .  .  .   .  S.  Jb.,  cli. 

LABBEE A.  G.  M.,  1870,  xvi.  338. 

ANSTIE  and  ANDREWS  .  Amer.  Journ.  Insan- 
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ANDREWS  and  DA  COSTA  .  A.  J.  M.  S.,  April, 
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KOBERT T.  G.,  1887. 

RINGER  and  SAINSBURY  .  B.  M.  J.,  March; 
1883. 

CERNA     U.  M.  M.,  Nov.  1891. 

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PEISER Thesis,  Halle,  1892. 

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WERTHEIMER  and  LEPAGE  .  E.  M.  N.,  1903. 


SOMNIFACIENTS. 


167 


REFERENCES. — Continued. 


13.  LEVINSTEIN  . 

23.  LlEBREICH      . 

24.  RUSSELL     .  . 

25.  BECK    .... 

26.  MACNAMARA 

27.  WIDENHOFER 

28.  HALL    .... 

29.  PLAYFAIR   .  . 


31- 


32.  CLEMENS 

33.  STONE  .  . 


34.  BOOTH  .  . 

35.  BRUNTON 

36.  KIRN    .  . 

37.  SMITH  .  . 

38.  KIRN    .  . 

39.  SCHULE   . 


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.  Gl.  M.  J.,  Feb.  1860. 

.St.  L.  M.  S.  J.,  June,  1872. 

.  Practitioner,  Nov.  1874. 

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.  L.  L.,  May  2,  1874. 

.  L.  L.,  1874,  i. 

N.  Y.  M.  J.,  xxxvii.  445. 
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Chirurgicale,  etc.,  Paris, 

1875- 

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179-. 

.  L.  L.,  1884,  i.  468. 
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.  B.  K.  W.,  xx.  721. 
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CHAPMAN   .  .  .  .  L.  L.,  1871. 

ELLIOTT L.  L.,  1873,  i.  754. 

REYNOLDS  ....  Practitioner,  March,  1870. 

WATSON M.  and  S.  Rep.,  Jan.  27, 

1871. 

FULLER L.  L.,  March,  1871. 

SCHWAIGHOFER  .  Irish  Hosp.  Gaz.,  1873. 
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and  Pharmacy,  1872,  254. 
B.  K.  W.,  1876. 

VULPIAN     .   .   .   .  C.  R.  S.  B.,  Ixxxvi.  1303. 
SULPHONAL. 

KAST B.  K.  W.,  1888. 

BAUMANN  and  SALKOWSKI  .  C.  M.  W.,  1892, 

XXX. 

B.  M.  J.,  1898,  ii. 

NEISSER S.  Jb.,  ccxxxi. 

PETITT M.  News,  1899,  Iv. 

HOPPE-SEYLER  and  RITTER  .  S.  Jb.,  ccxxvii' 

194. 

ANDREWS  .  .   .  .  J.  A.  M.  A.,  1892. 
DAUTHVILLE    .  .  Thesis,  Paris,  1889. 
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10.  GARROD  and  HOPKINS  .  J.  P.  and  B.,  1895-96. 

iii. 

11.  STOKVIS S.  Jb.,  ccxlviii. 

12.  KAST  and  WEISS  .  B.  K.  W.,  1896,  xxxiii. 

13.  HERTING    .  .   .  .  S.  Jb.,  1894,  ccxliv. 

14.  MULLER W.  K.  W.,  1894,  252. 

15.  ERBSLOH    .  .  .  .  D.  Z.  N.,  1903. 

TRIONAL. 

1.  BERGER M.  M.  W.,  1895. 

2.  COLLATZ     .  .   .  .  B.  K.  W.,  1893. 

3.  WIGHTWICK  and  ROLLESTON  .  L.  L.,  1903,  i. 

1096. 

4.  HAENKL Psycholog.  Arbeit.,  1897,  ii. 

5.  EGASSE B.  G.  T.,  1894,  ii. 

6.  KRONFELD    .  .  .  W.  M.  Bl.,  1898,  xxi. 

PARALDEHYDE. 

1.  BOKAI  and  BARCSI  .  P.  M.  C.  P.,  1885-86. 

2.  CAPPELLI  and  BRUGIA  .  A.  I.  M.  N.,  1886,  i. 

3.  DRAGE L.  L.,  Sept.  1900. 

4.  RAIMANN    ....  W.  K.  R.,  1899,  Nos.  19,  20, 

21,  22. 

5.  PROBST M.  P.  N.,  1903,  Bd.  xiv. 

6.  V.  A.  S.,  1887,  xiv. 
7-  Cb.  N.,  1900,  S.  139. 

MINOR  HYPNOTICS. 

1.  HOUGHTON  and  ALDRICH  .  J.  A.  M.  A.,  Sept. 

23,  1899. 

2.  SINKLE-R T.  M.,  July,  1901. 

3.  DONALD T.  G.,  Jan.  1900. 

4.  WADE J.  N.  M.  D.,  1900. 

5.  LANGGAARD  .  .   .  Th.  M.,  1889. 

6.  HALASZ W.  M.  W.,  1889. 

7.  HAGEMANN  and  HUFLER  .  M.  M.  W.,  iSi;. 

8.  HANRIOT  and  RICHET  .  C.  R.  S.  B.,  1893. 

9.  LIEBREICH    .  .   .  B.  M.  J.,  Dec.  1873;  Feb. 

1876. 

10.  LAHOUSSH  .  .   .   .A.  Pharm.,  1895,  i. 

11.  SCHMIDT    ....  Cb.  C.,  1877,  210. 

12.  SCHMIEDEBERG     .  A.  E.  P.  P.,  XX.  210. 

13.  VON  MERING  and  THIERFELDER  .  Z.  P.  C., 

1885,  1.  9. 

14.  IMPENS T.  M.,  Sept.  1903. 

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16.  TRAUTMANN     .  .  Ther.  Geg.,  1903. 


FAMILY   IV.— DELIRIFACIENTS. 


IN  the  present  group  are  considered  medicines  whose  preparations, 
when  taken  into  the  system,  cause  marked  dilatation  of  the  pupil  and  act 
upon  the  cerebral  nerve-cells  so  as  to  produce  delirium. 

BELLADONNA  FOLIA— BELLADONNA  LEAF.  U.  S. 
BELLADONNA  RADIX— BELLADONNA  ROOT.  U.  S. 

The  leaves  and  root  of  Atropa  Belladonna,  an  herbaceous  perennial, 
a  native  of  Europe,  but  cultivated  in  this  country,  and  attaining  a  height 
of  some  three  feet.  The  dried  leaves  are  oval,  entire,  on  a  short  foot- 
stalk ;  they  have  a  faint  narcotic  odor,  and  a  sweetish,  sub-acrid,  slightly 
nauseous  taste.  The  dried  cylindrical  branched  root  is  from  one  to 
several  inches  in  diameter,  much  longer,  fibrous,  externally  reddish 
brown,  internally  whitish,  almost  odorless,  with  a  very  feeble  sweetish 
taste. 

The  dominant  alkaloids  of  belladonna  are  hyoscyamine  and  atropine, 
belladonnine  and  other  alkaloids,  whose  isolation  from  it  has  been  alleged, 
being  either  present  in  exceedingly  minute  quantities  or  derivatives  from 
the  more  important  alkaloids.  There  is  even  much  reason  for  believing 
that  atropine  itself  is  a  secondary  product  derived  from  hyoscyamine, 
chiefly  during  the  process  of  manufacture.  The  toxic  effects  and  the 
therapeutic  uses  of  belladonna  are  those  of  atropine,  which  alkaloid  should 
always  be  preferred  to  the  cruder  preparations  of  the  drug  when  a  distinct 
physiological  effect  is  desired. 

ATROPINA.     U.  S. 

Atropine*  occurs  in  silky  prismatic  and  acicular,  often  aggregated, 
crystals,  of  a  bitter,  burning  taste,  without  odor,  practically  insoluble  in 
water,  and  therefore  always  used  in  the  form  of  the  sulphate.  It  is  most 
abundant  in  the  root,  and,  according  to  M.  Lefort,1  in  that  of  young  plants. 

PHYSIOLOGICAL  ACTION.  — Local  Action.  — Elimination. — Atropine  is 
not  irritant,  but  when  locally  applied  in  sufficient  concentration  is  probably 
paralyzant  to  most  of  the  higher  forms  of  protoplasm,  overpowering  the 
capillary  walls,  the  sensory  and  motor  nerves,  and  even  muscular  and 
glandular  cell-action.  A.  Zeller 2  has  found  that  a  one  per  cent,  solution 
of  atropine  brought  in  contact  with  the  blood,  outside  of  the  body,  checks 
the  movements  of  the  corpuscles. 

Atropine  is  absorbed  with  great  rapidity  from  the  primse  vise  and 
slowly  but  certainly  through  the  skin.  It  is  eliminated  in  great  part  or 
altogether  unchanged,  chemists  having  failed  to  find  in  any  secretion  the 

*  For  the  relations  of  atropine  to  other  mydriatic  alkaloids,  see  HYOSCINE,  page  187. 
168 


DELIRIFACIENTS.  169 

natural  decomposition  product,  ecgonin,  and  Wiechowski  having  re- 
covered, on  an  average,  thirty-three  per  cent,  of  the  injected  atropine  from 
the  urine.  It  has  been  found  in  all  the  tissues  of  the  poisoned  individual, 
and  S.  Fubini  and  O.  Bonanni 3  have  detected  it  in  the  milk,  but  it  chiefly 
escapes  by  the  kidneys  ;  hence  poisoning  may  often  be  diagnosed  by 
dropping  the  urine  of  the  patient  in  the  eye  of  a  cat  or  other  domestic  ani- 
mal, when  mydriasis  will  be  produced.* 

General  Action. — Usually  the  only  symptom  induced  in  man  by  the 
smallest  physiological  dose  of  atropine  (one-hundredth  to  one-sixtieth 
of  a  grain)  is  dryness  of  the  throat  and  mouth,  and  possibly  some  dis- 
order of  vision.  When  larger  amounts  are  given,  this  dryness  is  more 
intense,  and  is  associated  with  redness  of  the  fauces,  dilated  pupils,  dis- 
ordered vision,  and  possibly  diplopia.  The  pulse  is  sometimes  at  first 
rendered  less  frequent,  but  this  decrease  is  very  transient,  and  certainly 
in  many  cases  cannot  be  demonstrated  at  all.  After  a  toxic  dose  of  the 
alkaloid,  often  from  the  first,  certainly  always  in  a  short  time,  the  heart's 
beats  become  excessively  rapid,  the  pulse  rising  to  120,  or  even  160  ;  and 
in  a  little  while  a  peculiar  bright  red  flush  appears  on  the  face  and  neck, 
and  may  spread  over  the  whole  body.  This  erythema  resembles  the  rash 
of  scarlet  fever,  but  lacks  punctation,  and  is  usually  not  followed  by  des- 
quamation.  Early  in  atropine-poisoning  there  may  be  forcible  expulsion 
of  urine,  and  even  erections  of  the  penis  ;  later  there  is  urinary  retention. 
With  the  symptoms  above  enumerated,  intellection  may  remain  perfect ; 
but  there  is  generally  some  lightness  of  head,  giddiness,  and  confusion 
of  thought,  as  well  as  a  staggering  gait  and  restlessness.  Occasionally, 
even  medicinal  doses  cause  spectral  illusions.  Drowsiness  is  not  a 
usual  or  at  all  characteristic  symptom.  When  the  dose  has  been  suffi- 
cient there  develops  a  peculiar  talkative,  wakeful  delirium,  in  which 
the  patient  lives  in  a  world  of  his  own,  engrossed  by  spectres  and 
visions  which  throng  him,  and  completely  oblivious  to  the  surrounding 
realities.  Thus,  we  have  seen  a  lady  remain  for  a  long  time  stooping 
and  holding  fast  to  the  bed-post,  to  which  she  talked  in  the  most  voluble 
manner,  as  though  it  were  an  intelligent,  living  entity.  Sometimes  this 
delirium  is  wild,  and  the  patient  almost  uncontrollably  violent.  After 
a  time,  sleep  may  come  on,  and  on  waking  complete  consciousness 
may  be  regained,  or  the  symptoms  may  gradually  subside.  Lividity 
of  the  face  and  evident  imperfect  aeration  of  the  blood  are  not  seen 
in  atropine-poisoning,  except  in  the  stage  of  imminent  peril.  When 
an  enormous  dose  of  the  alkaloid  has  been  taken  a  fatal  stupor  with  mus- 
cular relaxation  may  develop  almost  at  once  ;  or  severe  convulsions 
may  appear  and  persist,  with  or  without  furious  maniacal  delirium. 
Probably,  however,  in  all  fatal  cases  stupor  and  muscular  paralysis 
finally  develop  ;  and  although  there  is  marked  failure  of  the  circula- 
tion, the  immediate  cause  of  death  is  asphyxia,  produced  by  depression 

*  For  a  chemico-physiological  study  of  tropine  and  other  derivatives  from  atropine, 
see  Archivf.  Exper.  Pathol.  u.  Pharm.,  v.  403. 


1 70  GENERAL  REMEDIES. 

both  of  the  respiratory  nerve-centres  and  of  the  respiratory  nerve-trunks. 
Congestion  of  the  lungs  and  of  the  membranes,  and  even  of  the  sub- 
stance of  the  brain  and  cord,  may  be  found  after  death,  and,  according 
to  M.  Lemattre,*  congestion  of  the  retina  is  an  almost  characteristic 
lesion. 

Upon  the  lower  animals  belladonna  to  a  great  extent  acts  as  upon 
man,  although  its  influence  is  much  less  powerful  in  them,  and  very  much 
larger  doses  are  required.  Seeming  differences  of  action  are  in  most 
cases  simply  apparent,  not  real. 

In  the  dog,  as  in  man,  the  pulse-rate  is  very  greatly  increased  by  atropine, 
while  in  the  rabbit  it  is  not.  As  will  be  shown  hereafter,  the  rise  of  the  pulse-rate 
caused  by  atropine  is  largely  due  to  paralysis  of  the  par  vagum.  Atropine  paralyzes 
the  par  vagum  in  the  rabbit  as  much  as  in  the  dog,  but  in  the  domestic  rabbit 
pneumogastric  paralysis,  by  section  or  otherwise,  is  never  followed  by  a  rise  of  the 
pulse-rate  at  all  comparable  to  that  seen  under  similar  circumstances  in  the  dog. 
Evidently  the  action  of  the  drug  is  identical  in  the  two  cases,  although  the  symptoms 
are  different.  In  their  sensitiveness  to  atropine  animals  differ  very  much,  and,  as 
a  general  rule,  herbivora  are  less  susceptible  than  carnivora.  Thus,  the  rabbit 
may  be  fed  for  days  entirely  upon  belladonna-leaves  without  injury,  and  many 
grains  of  atropine  are  necessary  to  kill  him.  Pigeons  we  have  found  will  often  re- 
cover after  the  hypodermic  injection  of  two  grains  of  atropine,  and,  according  to 
Fe're',  1.75  grammes  taken  by  the  mouth  will  not  kill  a  hen  of  2.9  kilogrammes' 
weight.  A  very  curious  fact,  which  we  have  repeatedly  verified,  is  that  the  pupils 
in  pigeons  cannot  be  dilated  by  the  use  of  belladonna.  According  to  Richet,  the 
monkey  offers  an  extraordinary  resistance  to  the  action  of  atropine. 

Circulatory  System. — Atropine  may  cause  a  primary  slowing  of  the 
pulse  (very  brief  and  only  to  be  occasionally  demonstrated),  followed  by 
an  extraordinarily  rapid  pulse,  with  a  very  great  rise  in  the  arterial  press- 
ure ;  followed  after  a  time,  if  the  dose  have  been  sufficient,  by  a  progres- 
sive lowering  of  pressure  until  death  is  reached,  the  rapidity  of  the  pulse 
being  maintained  until  the  end. 

As  in  atropinized  animals  neither  section  nor  galvanization  of  the  vagi 
affects  the  pulse-rate,  the  increase  of  the  pulse-rate  must  be  largely  due 
to  paralysis  of  the  trunk  or  of  the  peripheral  endings  of  the  vagi.  The 
primary  fall  of  the  pulse,  in  accordance  with  the  experiments  of  Bezold 
and  Bloebaum,4  is  due  to  stimulation  of  the  inhibitory  cardiac  centre  ; 
these  observers  having  found  that  when  atropine  is  injected  into  the 
carotid  so  as  to  reach  the  pneumogastric  centres  before  the  pneumogastric 
nerve-endings,  there  is  instantaneously  a  great  fall  in  the  rate  of  the  heart's 
beat.  Of  course,  in  the  fully  atropinized  animal  any  effect  of  the  drug 
upon  the  inhibitory  centres  is  masked  by  the  inability  of  the  paralyzed 
vagi  to  carry  impulses  from  the  centre,  and,  in  fact,  only  in  especial  cases 
is  the  primary  slowing  manifested,  f 

*  Quoted  by  Tardieu  (Sur  I'Empoisonnement,  Paris,  1867,  752). 

t  See  Stille's  Therapeutics,  \.  725.  Mitchell,  Keen,  and  Morehouse  found  it  in  about 
one-third  of  the  cases  after  large  hypodermic  injections,  Da  Costa  in  a  large  proportion 
(Amer.  Journ.  Med.  Set.,  July,  1865),  and  Miss  Mary  Putnam  in  some  cases  (New  York 
Medical  Record,  1873). 


DELIRIFACIENTS.  171 

By  large  doses  of  atropine  both  the  batrachian  and  mammalian  heart 
are  depressed  and  arrested  in  diastole,  out  of  which  they  cannot  be  aroused 
by  stimulation  ;  and  Bezold  and  Bloebaum  have  found  that  after  section 
of  the  spinal  cord  and  vagi  full  doses  of  atropine  lessen  at  once  the 
arterial  pressure.  It  is  therefore  established  that  overwhelming  doses  of 
atropine  act  as  a  direct  paralyzant  upon  the  heart-muscle. 

The  question  as  to  the  effect  of  small  doses  has  been  much  debated, 
but  probably  very  minute  quantities  exert  a  feeble,  stimulating  influence 
upon  the  mammalian  heart  ;*  thus,  Ramson  discovered  that  atropine 
causes  in  the  heart  of  the  octopus  excitation  of  the  muscular  fibre  ;  O. 
Langendorff 5  found  that  when  the  cut-off  apex  of  the  frog's  heart  was 
touched  with  a  minute  quantity  of  atropine  it  immediately  commenced  to 
beat ;  f  and  G.  Beyer 7  noticed  that  the  ventricles  of  the  isolated  terrapin' s 
heart  are  stimulated  by  minute  quantities  of  the  alkaloid,  although  they 
are  arrested  in  diastole  by  larger  amounts.  This  action  of  the  drug  upon 
the  heart-muscle  is  probably  the  cause  of  the  increased  pulse-rate  which 
has  been  noted  as  occurring  when  atropine  is  given  after  division  of  the 
vagi,  although  it  is  possible  that  this  increase  is  due  to  stimulation  of  the 
accelerators.  J 

The  recorded  evidence  obtained  by  the  direct  observation  §  of  the  capil- 
laries under  the  microscope  during  poisoning  of  frogs  by  atropine  is, 
on  the  whole,  in  favor  of  the  view  that  minute  doses  of  atropine  cause 
contractions  of  the  vessels  ;  but  much  more  decisive  proof  is  to  be 
obtained  as  to  the  effect  of  atropine  upon  the  vaso-motor  system  by  a 
study  of  the  arterial  pressure.  It  was  first  proved  that  the  alkaloid  is 
powerless  to  produce  rise  of  the  arterial  pressure  after  separation  of  the 
vaso-motor  centres,  by  high-up  section  of  the  spinal  cord,  from  the  blood- 
vessels of  the  body,  by  Bezold  and  Bloebaum,  whose  statements  were  con- 
firmed in  1873  by  H.  C.  Wood.8  Further,  Bezold  and  Bloebaum  have 
found  that  when  a  small  dose  of  atropine  is  injected  into  the  carotid  artery, 
— that  is,  into  the  vaso-motor  centres, — there  is  an  instantaneous  rise  of 
pressure.  There  can  be  no  doubt  that  the  chief  factor  in  the  great  rise 

*  Harnack  (Archivf.  Exper.  Pathol.  Pharm.,  ii.  328)  finds  that  the  minutest  dose  of 
atropine  increases  the  rapidity  of  the  heart's  action  after  stimulation  of  its  inhibitory 
centres  by  muscarine  and  consequent  slowing  of  its  beat. 

t  The  reports  as  to  the  action  upon  the  rate  of  the  frog's  heart  are  somewhat  at  variance, 
Eowditch  and  Luciani  having  noted  an  increase,  Gnauck  6  a  lessening,  in  the  cardiac  pul- 
sations (  Verhandl.  Physiolog.  Gesellsch.  zu  Berlin,  1881).  H.  Schapiro  states  that  this 
variance  is  accounted  for  by  the  fact  which  he  has  discovered,  that  whereas  at  high  tem- 
perature (15°  C.)  the  pulsations  are  diminished,  at  low  temperature  (7°  C.)  they  are 
increased. 

J  See  University  Med.  Magazine,  May,  1891 . 

$  A  fuller  discussion  of  this  subject  may  be  found  in  the  tenth  edition  of  this  book.  It 
is  omitted  here  because  we  do  not  think  that  evidence  of  this  character  is  of  much  im- 
portance. The  contraction  of  the  capillaries  by  a  local  application  may  be  the  result  of 
mechanical  or  other  irritation.  Moreover,  the  alterations  in  the  calibre  of  the  vessels  are 
so  slight,  and  are  so  apt  to  occur  from  other  causes  than  the  drug  given,  as  to  leave 
great  play  for  the  imagination  of  the  observer, — a  source  of  fallacy  whose  importance  is 
indicated  by  the  ever-varying  results  obtained  by  the  different  investigators. 


172  GENERAL  REMEDIES. 

of  arterial  pressure  produced  by  atropine  is  a  stimulating  influence  upon 
the  vaso-motor  centres. 

The  final  fall  of  blood-pressure  in  atropine-poisoning  is  due  to  its  de- 
pressing influence  upon  the  heart-muscle  and  upon  the  muscles  in  the 
walls  of  the  capillaries.  The  local  application  of  the  alkaloid  to  the  web 
of  the  frog's  foot  is  soon  followed  by  a  complete  paralytic  dilatation  of 
the  vessels  ;  further,  Bezold  and  Bloebaum  have  found  that  in  atropine- 
poisoning  the  arterial  muscular  coats  finally  lose  their  irritability,  but  that, 
so  long  as  they  retain  it,  galvanic  stimulation  of  a  sympathetic  nerve  does 
not  fail  to  induce  contraction  in  the  tributary  vessels. 

Cerebrum. — The  delirium  which  is  so  characteristic  of  atropine-poison- 
ing shows  that  it  has  especial  relations  with  the  cerebral  cortex.  Alber- 
toni 9  finds  that  neither  the  single  large  dose  nor  the  repeated  continu- 
ous dose  has  any  power  in  preventing  the  epileptic  seizure  resulting 
in  dogs  from  the  stimulation  of  the  motor  zone  of  the  cortex  :  enor- 
mous toxic  doses  seem  only  to  render  the  response  slower  and  less  vivid. 
The  influence  of  atropine  upon  the  psycho-motor  centres  would,  there- 
fore, appear  to  be  slight.  It  should  be  noted  that  atropine  is  not  in  a 
proper  sense  hypnotic,  the  stupor  which  it  produces  being  due  to  an 
overwhelming  of  the  cerebral  cortical  centres,  and  not  being  preceded  by 
sleep. 

Motor  Nerves. — The  original  discoveries  of  S.  Botkin,10  that  tying  the 
vessels  of  a  frog's  leg,  so  as  to  shut  off  access  of  atropine  to  the  nerve, 
interferes  with  the  development  of  paralysis  during  the  poisoning  in  such 
leg,  and  that  the  nerves  after  death  from  atropine-poisoning  have  in  the 
frog  largely  lost  their  power  of  responding  to  galvanic  currents,  have  been 
abundantly  confirmed  by  Lemattre,  by  Bezold  and  Bloebaum  (Joe.  cit., 
20),  by  Meuriot,11  by  Eraser,  and  others.  Although  in  mammals  a 
notable  amount  of  functional  power  is  retained  by  the  motor  nerve  up  to 
death  from  atropine,  yet  it  is  demonstrated  that  atropine  is  a  distinct 
depressant  to  the  motor  nerves,  both  in  the  higher  and  in  the  lower  ani- 
mals ;  and,  according  to  Bezold  and  Bloebaum,  both  the  nerve-trunks 
and  the  peripheral  intra-muscular  nerve-endings  are  affected.  All  experi- 
menters agree  that  no  stage  of  super- excitability  preceding  that  of  depres- 
sion can  be  discovered. 

Sensory  Nerves. — The  action  of  atropine  upon  the  sensory  nerves  is 
similar  to  its  influence  upon  the  motor  nerves,  although  less  powerful.* 
S.  Botkin  found  that  if  in  the  atropinized  frog  the  nerve  of  one  leg  had 
been  protected  from  the  poison  by  tying  the  artery,  irritation  of  the  foot 
of  the  non-protected  leg  at  a  time  when  that  leg  was  completely  paralyzed 
would  cause  spasm  in  the  opposite  limb  whose  motor  nerve  was  pro- 
tected ;  yet  later  in  the  poisoning,  although  irritation  of  the  foot  of  the 
protected  leg  would  cause  movement  in  that  leg,  no  irritation  of  the  op- 

*  For  objections  to  Miss  Mary  Putnam's  paper  ( N.  Y.  Med.  Rec.,  1873),  which  would 
indicate  that  the  sensitive  nerves  are  especially  affected  by  atropine,  see  tenth  edition  of 
this  treatise. 


DELIRIFACIENTS.  173 

posite  poisoned  foot  was  able  to  induce  response,  showing  that  at  first  the 
sensory  nerve  was  intact  in  the  paralyzed  leg,  but  that  it  finally  suc- 
cumbed to  the  poison. 

Meuriot  found  that  if  a  frog  be  bound  tightly  around  the  body  so  as 
to  interrupt  the  circulation,  and  then  be  poisoned  by  atropine  in  the  front 
part  of  its  body,  at  first  irritations  in  any  part  will  give  rise  to  general 
spasms,  but  after  a  time  in  order  to  get  any  movements  of  the  hind  legs 
it  is  necessary  to  apply  an  irritant  to  them.  Again,  the  hinder  parts  of  a 
frog  were  so  bound  by  ligatures  as  to  cut  off  on  the  one  side  all  commu- 
nication except  by  the  nerves,  and  on  the  other  to  leave  free  the  nerve 
and  the  vessels.  A  large  injection  of  atropine  was  then  given,  and  when 
the  moment  came  that  irritation  of  the  periphery  of  the  leg  whose  circu- 
lation was  free  would  no  longer  cause  reflex  spasms,  the  artery  of  this  leg 
also  was  tied,  so  that  both  legs,  the  one  atropinized,  the  other  not,  were 
now  connected  with  the  body  of  the  frog  only  by  their  nerves.  Strych- 
nine was  given  hypodermically,  and  it  was  found  that,  while  irritation  of 
the  atropinized  leg  had  no  effect,  stimulation  of  the  non-atropinized  leg 
gave  rise  to  general  convulsions.  It  is  plain,  however,  that  the  influence 
of  atropine  upon  the  sensory  nerve  is  feeble  ;  for,  although  Botkin  con- 
firmed the  experiments  of  Bezold  and  Bloebaum,  he  found  that  immersion 
of  a  sciatic  nerve  for  some  little  time  in  a  two  and  a  half  per  cent,  solution 
of  the  alkaloid  did  not,  in  the  strychnized  frog,  prevent  the  nerve  trans- 
mitting the  impulse,  since  irritation  of  the  foot  would  produce  general 
convulsions. 

Spinal  Cord. — Thomas  R.  Eraser12  discovered  in  1869  that  if  a  frog 
receive  an  injection  of  about  one-thousandth  part  of  its  weight  of  atropine, 
a  condition  of  perfect  paralysis  and  abolition  of  reflex  action  comes  on 
after  a  time,  and  lasts  from  two  to  four  days,  to  be  succeeded  by  a  tet- 
anoid  stage,  with  violent  convulsions  of  spinal  origin  and  excessive  excita- 
bility of  the  reflex  centres.  For  reasons  given  in  full  in  the  tenth  edition 
of  this  treatise,  Fraser  came  to  the  conclusion  that  atropine  stimulates  the 
spinal  cord,  and  that  during  the  paralytic  stage  of  the  poisoning  this  con- 
dition of  the  cord  is  masked  by  the  paralyzed  state  of  the  efferent  nerves. 
This  conclusion,  however,  has  been  disproved  by  Ringer  and  Murrell, 
who  found  that  tying  an  artery  so  as  to  protect  the  nerve-trunks  from  the 
poison  did  not  hasten  the  development  of  the  tetanus  ;  and  also  showed 
that  in  some  poisoned  frogs  voluntary  and  reflex  action  return  before  the 
supervention  of  the  tetanus.  It  is  evident  that  both  paralysis  and  tetanus 
are  due  to  an  action  upon  the  spinal  centres,  the  drug  so  acting  upon  the 
spinal  cord  as  first  to  paralyze  and  then  intensify  its  reflex  activity.  The 
theory  approved  by  Ringer  and  Murrell,  that  both  the  paralysis  and  the 
tetanus  are  due  to  a  depressant  action  upon  this  cord,  is  plausible  and 
probably  correct. 

According  to  this  theory  the  spinal  cord  has  within  it  two  functions, 
motion  and  inhibition,  certain  cells  giving  off  motor  impulses,  certain 
nerve-fibres  inhibiting  these  motor  impulses.  In  the  normal  cord  the 


I74  GENERAL  REMEDIES. 

motor  cells  are  under  continual  inhibition  ;  under  the  influence  of  atropine 
it  is  believed  that  both  motor  and  inhibitory  functions  are  paralyzed  ;  hence 
the  general  paralysis.  After  a  time,  however,  the  motor  cells  recover 
themselves  so  as  to  be  able  to  generate  impulses  freely,  although  the  in- 
hibitory function  of  the  cord  is  still  depressed,  the  effect  being  an  appar- 
ently true  spinal  excitement,  which  is  due  to  lack  of  inhibition,  the  motor 
cells  being  actually  weak.  At  such  a  time  a  peripheral  impulse  reaching 
the  motor  cell,  instead  of  giving  rise  to  a  simple  reflex  action,  and  then 
being  inhibited,  passes  on  and  starts  a  series  of  reflex  movements  in- 
volving all  the  muscles  and  constituting  a  tetanic  convulsion.* 

The  experiments  of  Lemattre  indicate  that  belladonna  exerts  a  similar 
paralyzant  and  convulsant  action  in  mammals  ;  both  Eraser's  and  Reich- 
ert's  experiments  confirm  this.  It  is  very  certain  that  in  man  atropine 
exerts  this  double  influence,  for  the  records  of  poisoning  cases  are  at 
once  the  records  of  convulsions  and  of  paralysis.  It  would  seem  that 
early  profound  paralysis  occurs  when  a  very  large  dose  of  the  poison  has 
been  taken  in  a  concentrated  alkaloidal  condition,  and  consequently  has 
been  rapidly  absorbed  and  suddenly  precipitated  upon  the  nervous  system. 

Voluntary  Muscles. — The  voluntary  muscles  escape  unscathed  in  atro- 
pine-poisoning.  It  is  true  that  Lemattre  has  shown  that  the  contractility 
of  a  striated  muscle  may  be  destroyed  by  soaking  it  in  a  very  concen- 
trated solution  of  the  alkaloid  ;  but  long  before  any  such  action  can  take 
place  in  life  the  animal  is  killed  ;  consequently  after  death  from  belladonna 
the  contractility  of  the  voluntary  muscles  is  found  unimpaired. 

On  the  non-striated  muscles  the  action  of  atropine  is  pronounced, 
but  its  exact  nature  is  at  present  writing  somewhat  uncertain.  It  may, 
we  believe,  be  considered  proved  that  the  toxic  dose  of  atropine  finally 
depresses  all  non-striated  muscles  ;  the  original  assertion  of  Bezold  and 
Bloebaum,  that  this  paralysis  may  become  so  complete  that  the  strongest 
faradic  currents  are  unable  to  cause  movements  either  in  the  intestines, 
bladder,  uterus,  or  ureters,  being  probably  correct. 

The  uncertainty  is  as  to  the  effects  of  small  doses.  P.  Keuchel 1S 
seems  to  have  proved  that  by  a  certain  dose  of  atropine  a  condition  is 
reached  in  which,  although  the  peristaltic  movements  of  the  intestines 
are  active,  galvanism  of  the  splanchnic — the  inhibitory  nerves  of  the  in- 
testinal coats — fails  to  have  effect.  If  this  be  true,  atropine  paralyzes 
the  peripheral  inhibitory  intestinal  apparatus  precisely  as  it  does  that  of 

*  The  conjunction  of  excessive  irritability  with  lack  of  power  in  motor  cells  is  a  com- 
mon condition  in  hysteria  and  neurasthenia.  The  fact  discovered  by  H.  C.  Wood,  that 
choreic  movements  of  the  dog  are  increased  by  atropine  and  diminished  by  quinine, — an 
inhibitory  stimulant, — fits  very  well  with  the  theory  of  the  text,  and  also  with  the  further 
facts  discovered  by  E.  T.  Reichert,  that  if  a  dog  to  which  a  supra-fatal  dose  of  atropine 
has  been  given  be  kept  alive  by  artificial  respiration,  choreic  movements  occur  which  are 
arrested  by  intravenous  injections  of  quinine.  It  would  appear  that  choreic  movements 
are  the  result  of  inhibitory  weakness ;  that  atropine,  increasing  inhibitory  weakness,  in- 
creases choreic  movements ;  and  that  quinine,  stimulating  inhibition,  decreases  these 
movements ;  and  that  the  two  alkaloids,  so  far  as  inhibition  is  concerned,  are  directly 
antagonistic. 


DELIRIFACIENTS.  175 

the  heart.  I.  Ott u  states  that  very  minute  doses  of  atropine  prevent  the 
'production  of  peristalsis  by  salt  placed  upon  the  intestines,  whilst  large 
doses  exaggerate  the  action  of  the  salt.  Admitting  the  correctness  of 
the  experiments  of  Ott  and  Keuchel,  it  is  evident  that  atropine  first  stimu- 
lates the  intestinal  inhibitory  nervous  system  and  then  paralyzes  it.  This, 
moreover,  is  corroborated  by  the  fact  that  the  smallest  dose  used  by 
Keuchel  was  0.075  gram>  by  Ott  0.015  gram>  both  observers  experi- 
menting on  the  rabbit.  When  Ott  used  0.45  grain  he  got  the  same 
result  as  did  Keuchel. 

Respiration. — The  medicinal  dose  of  atropine  ordinarily  has  no  ap- 
parent effect  upon  the  respiration  ;  but  both  in  man  and  in  the  lower 
animals  the  toxic  dose  usually,  though  not  always,  accelerates  the  respi- 
ratory movements. 

Researches  upon  the  effect  of  atropine  upon  the  respiratory  movement*  of  air 
have  been  made  by  H.  C.  Wood,15  Heubach,16  E.  Orlowski,"  E.  Vollmer,18  and 
Unverricht.19  The  experiments  of  Heubach,  Orlowski,  Vollmer,  and  Unverricht 
were  made  upon  animals  under  the  influence  of  morphine  ;  H.  C.  Wood's  experi- 
ments were  upon  normal,  morphinized,  and  chloralized  dogs.  The  first  effect  of 
atropine  in  the  normal  animal  is  greatly  to  increase  the  respiratory  air-movement. 
This  primary  excitement  is  usually  soon  followed  by  a  decrease,  which  is  not,  how- 
ever, sufficient  to  overcome  the  first  rise  ;  so  that  the  air-movement  remains  for  a 
long  time  distinctly  above  the  normal.  In  the  chloralized  dog  the  effect  of  atro- 
pine in  increasing  air-movements  is  constant  and  pronounced.  In  H.  C.  Wood's 
experiments  (two  in  number),  as  also  in  Orlowski's  and  Unverricht's,  with  animals 
under  the  influence  of  opium,  no  increase,  but  rather  a  decrease,  in  the  air-move- 
ment was  the  result  of  injections  of  atropine.  In  Heubach' s  and  in  Vollmer' s 
experiments,  which  were  numerous,  atropine  distinctly  increased  the  air-movement 
in  the  morphinized  dog.  The  action  of  opium  upon  the  respiration  in  the  dog  is 
at  present  so  little  understood  that  the  question  of  the  centra-action  of  atropine  and 
morphine  is  entirely  apart  from  that  of  the  action  of  atropine.  There  is  also  reason 
for  believing  that  the  toxic  dose  of  atropine  paralyzes  the  peripheral  pneumogastric 
nerve  in  the  lungs,  since  in  profound  atropine-poisoning  no  marked  influence  is  ex- 
erted upon  the  respiratory  rhythm  by  section  of  the  pneumogastric. 

As  section  of  the  vagi  (Bezold  and  Bloebaum)  does  not  prevent  the 
increase  of  the  respiratory  air-movement  produced  by  atropine,  it  must 
be  concluded  that  atropine  is  a  centric  respiratory  stimulant,  which,  as 
has  been  determined  by  Reichert,  becomes  a  depressant  or  paralyzant 
when  in  toxic  dose. 

In  Reichert' s  experiments  it  was  found  that  if  a  dose  two  or  three  times  the 
minimum  lethal  dose  was  given  internally  to  the  dog,  the  animal  could  be  kept  alive 
for  hours  by  artificial  respiration  and  ultimately  recover.  During  the  period  of 
recovery  certain  remarkable  phenomena  habitually  recurred,  for  an  account  of 
which  the  reader  is  referred  to  Reichert' s  article. 

Glandular  System. — It  is  generally  believed  that  the  suppression  of 
secretion  in  the  salivary,  mucous,  and  sweat-glands  is  due  to  paralysis 
of  the  terminal  ends  of  the  nerves,  since  Keuchel  has  shown  that  stimu- 

*  See  Respiratory  Stimulants. 


176  GENERAL  REMEDIES. 

lation  of  the  chorda  tympani  fails  to  excite  the  flow  of  saliva,  while 
irritation  of  the  sympathetic  will  cause  secretion.  Mathews,*5  however, 
combats  this  theory,  and  believes  that  the  action  of  atropine  is  upon  the 
gland-structure,  asserting  that  paralysis  of  the  nerve  will  not  prevent 
secretion. 

Small  doses  of  atropine  sometimes,  but  not  always,  increase  the  flow 
of  urine.  After  the  toxic  dose  the  urine  may  be  at  first  augmented,  but 
is  usually  lessened  very  early,  and  may  finally  be  entirely  suppressed.* 
The  assertion  of  Meuriot,  that  the  urinary  secretion  rises  and  falls  in 
atropine-poisoning  with  the  arterial  pressure,  is  not  in  accord  with  the 
results  obtained  by  Walti,20  who  found  atropine  to  produce  in  the  rabbit, 
independently  of  its  action  upon  the  circulation,  a  steady  lessening  in  the 
urinary  secretion.  Harley 21  affirms  that  medicinal  doses  of  atropine  de- 
cidedly increase  the  solids  of  the  urine,  slightly  the  urea  and  uric  acid, 
very  markedly  the  phosphates  and  the  sulphates. 

Our  knowledge  of  the  action  of  atropine  upon  the  secretions  of  the 
alimentary  canal  is  very  imperfect.  It  has  been  a  matter  of  traditional 
and  clinical  belief  that  the  secretions  are  increased,  and  Harley  gives 
some  experiments  which  he  asserts  corroborate  this  ;  Meuriot,  on  the 
other  hand,  states  that  they  are  lessened.  We  cannot  find,  however, 
any  experiments  that  seem  to  us  decisive  ;  and  clinical  evidence  cer- 
tainly indicates  that  the  intestinal  secretions,  if  affected  at  all,  are  in- 
creased. 

Temperature. — In  moderate  doses  atropine  causes  a  pronounced  rise 
in  temperature,  but  in  very  large  decidedly  toxic  amounts  it  lessens 
animal  heat.  Thus,  in  the  dog,  Meuriot  has  obtained  an  augmenta- 
tion of  from  i°  to  3°  C. ,  and  Dume'ril,  Demarquay,  and  Lecomte  of 
4°  C.  In  fatal  poisoning  of  the  same  animal,  these  observers  have 
noticed  a  fall  respectively  of  5. 10°  and  3°  C.  In  man,  Meuriot,  in  the  use 
of  medicinal  doses,  has  observed  the  temperature  to  rise  0.5°  to  1.1°  C. , 
and  Eulenburg  0.5°  to  0.8°  C.  According  to  I.  Ott  and  C.  Collmar,"  this 
increase  is  independent  of  the  blood-pressure,  occurring  both  when  the 
pressure  is  elevated  and  when  it  is  depressed,  and  is  accompanied  by  a 
greater  increase  of  heat-production  than  of  heat-dissipation.  It  is  there- 
fore due  to  the  increased  heat-production,  which  is  the  result,  in  all  prob- 
ability, of  an  influence  upon  the  nerve-centres.  Ott  and  Collmar  believe 
that  this  influence  is  a  stimulation  of  the  thermo-genetic  centres  in 
the  spinal  cord,  and  that  the  rise  of  temperature  is  paralleled  by  that 
which  occurs  in  tetanus.  It  seems  to  us  more  probable  that  it  is  due  to 
paralysis  of  thermo-genetic  inhibition.  The  final  fall  of  temperature  in 
atropine-poisoning  is  probably,  at  least  in  part,  caused  by  the  vaso-motor 
paralysis. 

Eye. — In  all  animals  except  birds,  atropine  causes  mydriasis  with 
paralysis  of  accommodation  and  probably  lessening  intra-ocular  pressure. 

•  See  case  of  Gross  (loc.  cit.),  also  of  Morer  (Ann.  Soc.  de  Med.  de  Gand,  1873). 


DELIRIFACIENTS.  177 

The  dilatation  induced  by  the  local  application  of  atropine  is  not  due 
to  a  direct  action  of  the  drug  upon  the  muscular  fibres  of  the  iris  ;  for  as 
all  of  these,  both  the  radiating  and  the  circular,  are  of  the  same  nature 
(non-striated  \i\  mammals),  their  antagonism  is  simply  due  to  position  ; 
and  it  seems  inconceivable  that  mere  position  should  affect  the  relations 
between  a  muscle  and  a  drug.  Moreover,  Bernstein  and  Dogiel  (con- 
firmed by  G.  Engelhardt)  found  that  while  galvanic  irritation  of  the  oculo- 
motor nerve  was  unable  to  cause  contraction  of  the  pupil  in  the  atropin- 
ized  eye,  yet  when  the  electrodes  were  applied  to  the  eyes  in  such  a  way 
as  to  affect  directly  the  iris,  contraction  occurred, — phenomena  explain- 
able only  by  the  theory  that  the  nerve-endings  were  paralyzed,  while  the 
muscle  was  unaffected. 

The  statement  first  made  by  Wharton  Jones, M  that  the  reason  atropine  does  not 
dilate  the  pupils  of  birds  is  that  their  irides  have  no  radiating  fibres,  has  been  dis- 
proved by  the  beautiful  anatomical  researches  of  Alex.  Ivanoff  and  Alex.  Rollett M 
(confirmed  by  Johannes  Diegel 25) .  Although  Bonders  w  says  that  the  pupillary  action 
of  atropine  "is  slight  in  birds,  in  which  it  was  formerly  overlooked, "  in  our  own 
experiments  the  most  thorough  application  of  very  strong  solutions  to  the  eyes  of 
pigeons  has  had  no  distinct  effect.  According  to  the  experiments  of  Szpilman  and 
Luchsinger,  lack  of  action  of  atropine  is  probably  due  to  the  muscular  fibres  of  the 
irides  of  birds  being  non-striated.  In  the  oesophagus  of  the  bird  the  muscle  is  non- 
striated,  and  atropine  paralyzes  it ;  in  the  oesophagus  of  the  rabbit  the  muscle  is 
striated,  and  atropine  has  no  action  ;  in  the  cat  a  portion  of  the  oesophagus  has 
smooth  muscular  fibres,  a  part  striated,  and  the  former  is  paralyzed,  the  latter  un- 
affected, by  atropine." 

The  dilatation  of  the  pupil  by  the  local  application  of  atropine*  is 
certainly  independent  of  any  nerve-centres  farther  back  than  the  ciliary 
ganglion. 

This  is  proved  by  the  following  facts.  Claude  Bernard28  and  Lemattre  both 
have  found  that  atropine-mydriasis  occurs  in  animals  after  section  of  the  oculo-motor, 
and  we  have  seen  it  in  cases  of  complete  oculo-motor  paralysis  in  man.  It  also  takes 
place  after  section  of  the  trigeminus  or  of  the  cervical  sympathetic,  or  of  both  of 
these  nerves,  as  is  shown  by  the  testimony  of  numerous  observers  and  by  our  own 
experiments.  In  man  we  have  seen  it  after  paralysis  of  the  sympathetic.*9 

The  dilation  of  the  pupil  by  the  local  application  of  atropine  is  indepen- 
dent not  only  of  the  central  nervous  system,  but  also  of  the  ciliary  ganglion, 
and  is  due  to  an  action  exerted  directly  upon  the  nerve-endings  in  the  iris. 

The  experiments  of  Bernstein  and  Dogiel,  confirmed  by  Engelhardt,  already 
quoted,  are  in  themselves  almost  enough  to  establish  the  truth  of  this  proposition. 
More  direct  evidence  is  not,  however,  wanting.  Thus,  Vierordtf  has  found  that 
atropine  locally  applied  causes  mydriasis  after  the  removal  of  the  ciliary  ganglion. 


*  Contraction  of  the  pupil  before  dilatation  noticed  in  dogs  ( Reese)  and  rabbits  ( Ross- 
bach  and  Frohlich)  is  probably  caused  reflexly  by  the  irritant  action  of  the  atropine. 

t  Unfortunately,  the  only  notice  we  have  seen  of  this  capital  experiment  is  in  Her- 
mann's Grundriss  der  Physiologic.  No  reference  is  given,  and  we  have  been  unable  to 
find  the  original  paper. 


178  GENERAL  REMEDIES. 

I.  Hoppe so  has  discovered,  and  Y.  Valentin 31  has  confirmed  the  discovery,  that  in 
the  eye  of  the  frog  removed  from  the  body  atropine  will  produce  dilatation  of  the 
pupil.  According  to  Borelli,32  mydriasis  is  produced  by  the  alkaloid  when  applied 
to  the  eye  of  a  man  just  dead.  Lastly,  the  presence  of  the  alkaloid  in  the  humors 
of  the  atropinized  eye  has  been  proved  by  numerous  observers,  among  whom 
may  be  mentioned  Lemattre  and  Bonders,  who  have  found  that  the  liquids  removed 
from  such  an  eye  are  capable  of  causing  dilatation  of  the  pupil  of  another  eye. 

The  dilatation  is,  at  least  in  part,  due  to  paralysis  of  the  peripheral 
filaments  of  the  oculo-motor  nerve.  Both  Bonders  and  Stellwag  von 
Carion M  insist  that  the  paralysis  of  accommodation  is  proof  of  paralysis 
of  the  oculo-motor  nerve,  and  it  seems  to  us  they  do  so  with  truth. 
However  this  may  be,  there  is  abundant  direct  proof  that  the  oculo- 
motor fibres  are  paralyzed,  since  the  experiments  of  Griinhagen,  which 
prove  that  galvanization  of  the  exposed  oculo-motor  nerve  d  es  not 
affect  the  atropinized  pupil,  have  been  confirmed  by  Engelhardt M  and  by 
Rossbach  and  Frohlich.85 

It  is  probable  that  the  sympathetic  or  dilating  nerve-fibres  of  the  iris 
are  stimulated. 

Clinical  experience  certainly  shows  that  the  dilatation  produced  by  a  mydriatic 
is  not  merely  a  passive  movement  of  relaxation,  but  is  active,  capable  of  tearing  up 
inflammatory  adhesions  even  when  of  some  firmness.  Again,  the  dilatation  that 
occurs  after  the  paralysis  of  the  oculo-motor  nerve  in  man  and  after  its  destruction 
in  animals  is  not  at  all  equal  to  that  produced  by  atropine,  and,  indeed,  can  be 
largely  increased  by  the  action  of  the  drug ;  further,  in  the  eye  separated  entirely 
from  the  nerve-centres  (see  above)  atropine  still  causes  a  wide  dilatation  ;  facts 
which  necessitate  the  belief  either  that  the  alkaloid  acts  upon  the  sympathetic 
fibrillae  or  that  the  peripheral  fibres  of  a  nerve  are  in  themselves  nerve-centres, 
acting  upon  the  muscle  of  themselves  even  when  separated  from  their  centres.  It 
has  been  urged  against  the  view  here  taken  that  even  the  widest  artificial  mydriasis 
is  increased  by  galvanization  of  the  sympathetic.  De  Ruiter  states  the  contrary  ; 
but,  since  Griinhagen,  Hirschmann,  and  Engelhardt  separately  affirm  as  the  re- 
sult of  personal  experiment  the  correctness  of  the  asserted  fact,  it  must  be  ac- 
cepted. Granting  its  truth,  we  do  not  think  it  warrants  the  deduction,  since  it  is 
conceivable  that  an  agent  may  excite  the  peripheral  filaments  of  a  nerve  greatly, 
and  yet  not  to  such  a  point  that  they  will  be  incapable  of  further  excitation.  Schultz 
believes  there  is  in  his  experiments  no  stimulation  of  the  dilator  fibres,  because 
when  the  superior  cervical  ganglia  is  destroyed  and  time  allowed  for  the  degenera- 
tion of  the  peripheral  nerve-fibres,  atropine,  whilst  dilating  both  pupils,  does  not 
destroy  their  inequality.  This  does  not,  however,  seem  to  us  to  prove  Schultz's 
conclusion,  for  it  may  well  be  that  it  is  the  intramuscular  endings  of  the  sympathetic 
nerve  which  is  stimulated  rather  than  the  sarcolemma  of  the  muscles  themselves, — 
a  theory  rendered  more  probable  by  the  fact  that  Schultz  found  that  pieces  of  the 
iris  of  a  cat,  when  exposed  to  a  five  per  cent,  solution  of  atropine,  did  not  lose  their 
irritability. 

A  priori,  it  is  strongly  to  be  expected  that  the  action  of  atropine 
upon  the  pupil  will  be  the  same  whether  it  is  carried  to  the  pupil  by  the 
blood  or  is  applied  locally  by  the  surgeon.  The  correctness  of  this 
conclusion  is  shown  by  the  following  evidence.  Lemattre  asserts  that 
he  has  secured  mydriasis  in  normal  eyes  by  placing  in  them  aqueous 
humors  taken  from  dogs  poisoned  with  atropine  ;  others,  however,  have 


DELIRIFACIENTS.  179 

failed  to  get  the  dilatation.  It  has  been  asserted  by  authorities,  and  ex- 
perimentally corroborated  by  H.  C.  Wood,  that  atropine  given  hypo- 
dermically  caused  dilatation  of  the  pupil  in  the  lower  animals  after  section 
both  of  the  trigeminus  within  the  skull  and  of  the  sympathetic  in  the 
neck  ;  H.  C.  Wood  has  shown  that  this  also  occurs  after  such  section  of 
the  parts  behind  the  eye  up  to  the  optic  nerve  as  secures  complete  isola- 
tion of  the  iris  from  any  nerve-centre.  What  is  true  of  the  lower  animals 
is  also  true  of  man  ;  accident  having  afforded  H.  C.  Wood  the  opportunity 
to  give  atropine  hypodermically  to  a  man  whose  eye  had  been  separated 
from  all  connection  with  the  nerve-centres,  it  was  found  that  the  pupil 
was  still  dilated  by  the  drug.* 

Our  knowledge  of  the  action  of  atropine  upon  the  pupil  may  be 
summed  up  as  follows.  Atropine  applied  locally  causes  mydriasis  by 
paralyzing  the  peripheral  ends  of  the  oculo-motor  nerve,  and  probably 
by  stimulating  the  peripheral  ends  of  the  sympathetic.  Atropine  given 
internally  causes  mydriasis,  not  by  influencing  the  nerve-centres,  but  by 
being  carried  in  the  blood  to  the  eye  itself  and  there  acting  precisely  as 
when  applied  locally. 

SUMMARY. — In  full  medicinal  doses  atropine  produces  a  sort  of 
febrile  state,  -with  dryness  of  the  mouth,  dilatation  of  the  pupil,  in- 
creased rapidity  and  force  of  the  circulation,  quickened  respiration, 
elevation  of  temperature,  and  secretion  of  febrile  urine.  The  toxic  dose 
intensifies  the  symptoms  just  narrated,  and  adds  to  them  a  peculiar 
wild  delirium.  The  stage  of  excitement  may  be  many  hours  long,  -with 
very  rapid  heart-action  and  high  arterial  pressure ;  after  a  time  it  is 
followed  by  one  of  general  functional  failure,  marked  by  stupor,  fall  of 
blood-pressure,  depression  of  reflexes,  and  death  from  asphyxia.  The 
cerebral  symptoms  are  due  to  direct  influence  of  the  alkaloid  upon  the 
cerebral  cortex.  The  primary  increase  of  respiration  is  the  outcome 
of  centric  stimulation ;  the  terminal  depression  and  asphyxia  are  pro- 
duced by  secondary  depression  of  the  respiratory  centre,  and  espe- 
cially by  depression  of  the  respiratory  nerves.  Upon  the  spinal  cord 
the  therapeutic  dose  probably  has  no  influence,  but  the  toxic  dose  acts 
as  a  depressant,  affecting,  however,  more  powerfully  the  motor  nerve- 
trunks  than  it  does  the  spinal  centre  and  to  a  less  degree  the  sensory 
nerves.  There  is  some  reason  for  suspecting  that  the  drug  primarily 
acts  as  a  feeble  stimulant  to  the  various  inhibitory  centres,  but  its 
pronounced  characteristic  effect  is  that  of  a  paralyzant  of  peripheral 
inhibition,  acting  in  this  way  upon  the  spinal  cord  itself,  upon  the  pneu- 
mogastric  nerve,  and  upon  the  splanchnics  so  as  to  increase  intestinal 
peristalsis.  The  rapid  pulse  is  chiefly  the  outcome  of  a  paralyzed  in- 
hibition, although  the  heart  may  be  feebly  stimulated.  The  primary 
rise  of  blood-pressure  produced  is  chiefly  due  to  stimulation  of  the 
vaso-motor  centres,  although  probably  the  work  of  the  heart  itself  is 
increased.  The  final  fall  of  pressure  is  due  to  depression  of  the  heart 
and  of  the  muscular  coats  of  the  vessels,  which  is  part  of  a  general 
action  upon  non-striated  muscle-fibres,  and  which  results  in  suspension 
of  intestinal  peristalsis  and  in  retention  of  urine. 

*  For  elaboration  of  details,  see  tenth  edition  of  this  book. 


i8o  GENERAL  REMEDIES. 

THERAPEUTICS. — In  practical  medicine  atropine  is  employed  in  direct 
conformity  to  its  physiological  action,  so  that  its  use  is  best  discussed 
under  the  headings  of  the  various  indications  to  meet  which  it  may  be 
administered. 

To  relax  Spasm. — As  the  powers  of  atropine  to  relax  spasm  de- 
pend on  its  influence  upon  the  peripheral  nerve-filaments  and  the  muscle- 
tissue,  it  is  evident  that  it  is  a  practical  remedy  only  in  those  cases 
in  which  the  spasm  is  due  to  some  local  cause  connected  with  a  mus- 
cle or  its  supplying  nerve  ;  hence  it  has  been  found  especially  useful  in 
rheumatic  torticollis,  in  the  violent  contractures  and  spasms  sometimes 
accompanying  neuritis,  and  especially  such  as  follow  nerve-wounds.  It 
is  essential  to  inject  the  alkaloid  directly  into  the  contracted  muscle,  so  as 
to  get  its  concentrated  influence  upon  the  affected  nerve  and  muscle,  little 
or  no  relief  usually  being  produced  by  so  small  an  amount  of  the  remedy 
as  would  reach  the  diseased  part  after  absorption  through  the  blood. 
The  non-striated  muscles  are  more  affected  by  the  atropine  than  the 
striated,  and  consequently  the  drug  is  found  to  be  more  efficacious  in 
spasm  of  the  involuntary  than  of  the  voluntary  muscles.  It  is  serviceable 
in  lead  colic,  in  simple  spasmodic  colic,  in  spasmodic  dysmenorrhcea,  in 
spasmodic  constriction  of  the  bowels  with  obstinate  constipation,  in  laryn- 
gismus  strididus,  in  nervous  coiigh,  in  asthma,  in  hiccough,  and  in  whooping- 
cough,  in  which  last  disease,  as  originally  advised  by  Bretonneau,  it  has 
been  largely  used  ;  also,  even  in  the  spasms  accompanying  the  passage 
of  renal  and  biliary  calculi,  where  of  course  it  usually  fails.  Wherever  it 
is  possible,  it  should  be  used  locally  in  spasm  of  the  involuntary  as  well 
as  of  the  voluntary  muscles.  Thus,  in  spasm  of  the  urethra,  the  ointment 
should  be  rubbed  in  along  the  canal  ;  in  rigid  os  uteri,  the  extract  should 
be  applied  directly  to  the  os  ;  in  asthma,  belladonna  should  be  inhaled, 
by  means  either  of  the  cigarette  or  of  the  atomization  of  a  decoction  of 
the  leaves  ;  in  spasm  of  the  sphincter  ant  from  fissure  or  other  cause,  it 
should  be  applied  directly  to  the  part  by  poultice  or  ointment.  Under 
the  present  indication  may  be  considered  the  use  of  the  remedy  in  consti- 
pation. In  doses  of  one-quarter  to  one-half  grain  of  the  extract,  bella- 
donna is  of  great  service  as  an  addition  to  laxative  pills.  In  that  form  of 
incontinence  of  urine  in  children  in  which  the  real  cause  is  an  irritability 
of  the  bladder,  so  that  spasmodic  contraction  occurs  under  the  stimulus 
of  a  small  portion  of  urine,  the  continuous  use  of  large  doses  of  atropine 
is  often  of  great  service  by  reducing  the  irritability  of  the  walls  of  the 
bladder,  with  which,  owing  to  the  method  of  its  excretion,  the  alkaloid  is 
brought  in  local  contact. 

To  relieve  Pain. — In  accordance  with  its  known  physiological  action, 
atropine  is  of  very  little  value  for  the  purpose  of  relieving  pain,  unless 
such  pain  be  connected  with  spasm,  or  unless  the  pain  be  due  to  ulcera- 
tion  or  other  local  cause  so  situated  that  the  atropine  can  be  brought  in 
direct  contact  in  concentrated  form  with  sensory  nerve-endings. 

To  impress  the  Heart  and  Blood-  Vessels. — In  certain  diseases,  such  as 


DELIRIFACIENTS.  181 

pneumonia,  congestion  of  the  lungs,  etc. ,  in  which  the  local  affection  is 
closely  connected  with  dilatatien  of  the  blood-vessels,  Harley  has  highly 
commended  atropine  as  a  vaso-motor  contractant.  In  most  of  these 
affections,  however,  the  remedy  has  failed  to  establish  itself.  In  acute 
coryza  and  angina  it  acts  most  favorably,  its  influence  upon  the  circulation 
being  probably  supported  by  its  specific  action  upon  the  glandular  appa- 
ratus of  the  mucous  membranes  involved,  and  possibly  by  its  relaxing  the 
pharyngeal  muscles. 

As  a  stimulant  to  the  circulation,  belladonna  has  probably  not  been 
employed  as  much  as  it  ought.  Graves,  however,  commends  it  especially 
when  the  pupil  is  contracted  in  typhus  fever,  and  it  has  been  used  with 
asserted  advantage  in  erysipelas,  scarlet  fever,  etc.  In  cases  of  sudden 
collapse  occurring  in  acute  disease  and  marked  by  falling  of  the  tempera- 
ture below  normal,  with  great  loss  of  the  arterial  tension  and  free  sweat- 
ing, atropine  is  of  the  greatest  value.  Such  collapse  is  not  infrequent  in 
young  children  in  the  advanced  stages  of  pneumonia,  pleurisy,  or  other 
pulmonic  disease,  and  is  also  prone  to  happen  in  puerperal  mania  and 
similar  maniacal  states  occurring  in  exhausted  patients.  It  is  similar  in 
its  character  to  that  which  is  produced  by  perforations  of  the  stomach  or 
intestine  or  as  the  result  of  surgical  or  accidental  traumatisms.  It  is  a 
condition  of  shock  in  which  the  loss  of  temperature  is  chiefly  the  result 
of  vaso-motor  paralysis.  Proper  treatment  of  this  condition  consists 
chiefly  in  the  free  use  of  external  heat  and  the  hypodermic  injection  of 
atropine,  strychnine,  and  the  tincture  of  digitalis  ;  in  many  of  these  cases 
alcoholic  stimulants  are  worse  than  useless. 

To  arrest  Secretion. — In  mercurial  salivation  atropine  arrests  almost 
at  once  the  discharge  of  saliva,  and  seemingly  facilitates  greatly  the  return 
to  health.  In  colliquative  sweats,  as  originally  recommended  by  Da 
Costa,86  it  is  probably  the  most  valuable  known  remedy.  One-sixtieth  to 
one- eightieth  of  a  grain  of  atropine  used  hypodermically,  at  bedtime, 
will  very  frequently  prevent  the  usual  night-sweat.  In  colliquative  diar- 
rhoea it  has  been  recommended  by  M.  Delpage,  and  very  probably  will 
be  found  of  service.  Inunctions  of  the  breast  with  belladonna  ointment 
are  habitually  employed  for  the  purpose  of  arresting  the  secretion  of  milk, 
and  in  the  experiments  of  Hammerbacher S7  upon  a  goat,  atropine  given 
internally  lessened  the  secretion,  especially  of  the  watery  portions  of  milk. 

Employment  in  Poisoning. — It  is  stated  that  as  far  back  as  1570  it  was 
affirmed  that  opium  and  belladonna  are,  in  their  influence  upon  the  sys- 
tem, antagonistic.  In  the  early  part  of  the  present  century  their  em- 
ployment as  counter-poisons  was  again  brought  prominently  before  the 
profession  ;  but,  although  a  few  scattered  earlier  records  of  their  use  as 
such  exist  in  medical  literature,  it  was  not  until  the  paper  of  William  F. 
Norris38  appeared  that  general  attention  was  attracted  to  the  subject. 
After  nearly  twenty- five  years  of  discussion,*  the  opinion  given  in  the 

*  For  an  account  of  this  discussion,  see  tenth  edition  of  this  treatise. 


182  GENERAL  REMEDIES. 

first  edition  of  this  work,  that  the  two  drugs  are  not,  strictly  speaking, 
antagonistic,  has  become  a  certainty.  Atropine,  is,  however,  a  valuable 
remedy  in  opium-poisoning  as  a  powerful  and  prompt  respiratory  stimu- 
lant. In  protracted  opium- narcosis  the  cardiac  and  vaso- motor  actions 
of  atropine  are  of  service  ;  but  it  should  never  be  forgotten  that  the  main 
influence  for  good  is  upon  the  respiratory  centres.  The  first  improve- 
ment from  atropine  in  these  cases  is  usually  increased  frequency  of  respi- 
ration ;  and  as  the  breathing  becomes  less  embarrassed  the  other  symp- 
toms ameliorate,  largely  because  of  the  increased  aeration  of  the  blood. 

The  double  nature  of  profound  opium-narcosis  must  not  be  lost  sight 
of  :  the  blood  is  saturated  with  carbonic  acid  almost  to  the  dead-line,  and 
much  of  the  unconsciousness,  much  of  the  failing  circulation,  much  even 
of  the  embarrassed  respiration,  is  due  to  the  presence  of  the  gas.  As 
soon  as  the  system  is  in  a  measure  relieved  of  this  load,  it  begins  to  re- 
bound ;  emetics  act,  consciousness  returns  to  some  extent,  the  circulation 
frees  itself,  and  the  road  leading  towards  health  is  entered  upon.  Atropine 
should  be  administered  as  soon  as  there  is  decided  failure  of  the  respira- 
tion. With  it  should  be  given  strychnine,  which,  as  was  first  pointed  out 
by  H.  C.  Wood,  is  at  least  equally  as  efficient  as  atropine.  Both  alkaloids 
should  be  given  hypodermically,  the  doses  being  large  but  not  toxic  :  one- 
fortieth  of  a  grain  of  atropine  and  one-fifteenth  of  strychnine  are,  in  most 
instances,  fair  commencing  doses.  Repetition  should  be  chiefly  guided 
by  the  effect  upon  the  respiration,  although  judgment  should  be  formed 
in  part  from  a  bird's-eye  view  of  the  whole  case.  No  more  of  the  alka- 
loids should  be  used  than  is  necessary  to  sustain  the  respiration  ;  so  long 
as  this  function  is  improving  they  should  be  withheld. 

Whenever  there  is  failure  of  respiration  in  other  poisonings  than  that 
of  opium,  atropine  in  conjunction  with  strychnine  is  useful.  It  has  been 
especially  commended  as  an  antidote  to  poisonous  fungi* 

As  a  Local  Sedative. — Locally  and  freely  applied,  belladonna  is  a 
sedative,  and,  we  believe,  to  glandular  as  well  as  to  muscular  and  nervous 
tissues.  In  this  way  it  is  often  very  useful  in  various  local  inflammations. 
In  the  form  of  a  plaster  it  frequently  appears  to  do  good  in  palpitation 
of  the  heart.  Its  use  locally  in  spasms  and  in  neuralgia  has  been  suffi- 
ciently dwelt  on.  In  mastitis,  its  local  application  to  the  breast  is  often 
very  efficacious.  Whenever  belladonna  is  used  locally,  in  order  to  get 
its  good  effects  it  must  be  employed  freely.  At  the  same  time,  it  should 
be  remembered  that  a  number  of  cases  of  poisoning  by  its  external  ap- 
plication have  been  reported.39'  *°  In  children  it  must  be  used  with  caution  ; 
in  adults,  with  a  reasonable  amount  of  care,  its  external  use  is  safe,  pro- 
vided directions  be  given  to  have  it  washed  off  so  soon  as  any  affection  of 
the  sight  or  dryness  of  the  throat  is  induced. 

Use  in  Diseases  of  the  Eye.  f — The  instillation  of  a  four  grains  to  the 
ounce  solution  of  atropine  sulphate  into  the  eye  is  followed  in  about 

*  Atropine  antagonizes  the  action  of  muscarine  (the  alkaloid  of  many  of  the  poisonous 
mushrooms)  on  the  cardiac  inhibitors  as  well  as  on  the  respiration. 

t  For  this  section  the  authors  are  indebted  to  Professor  George  E.  de  Schweinitz. 


DELIRIFACIENTS.  183 

fifteen  minutes  by  dilatation  of  the  pupil,  usually  reaching  its  maximum 
in  from  twenty-five  to  thirty-five  minutes,  and  lasting  until  the  third  day. 
In  about  twenty-five  minutes  the  power  of  accommodation  begins  to  be 
lost,  and  in  from  an  hour  and  a  half  to  two  hours  is  usually  fully  annulled  : 
return  begins  on  the  second  day,  but  the  function  may  not  be  fully  regained 
for  over  a  week. 

Atropine  is  used  by  ophthalmologists  :  First,  to  dilate  the  pupil  for 
purposes  of  ophthalmoscopy  and  to  expose  the  lens  in  cases  of  incipient 
cataract  so  that  all  portions  of  it  may  be  carefully  examined,  but  is  inferior 
in  this  respect  to  more  rapidly  and  fugacious  acting  mydriatics,  particu- 
larly a  four  per  cent,  solution  of  cocaine,  a  one  and  a  half  per  cent,  solution 
of  homatropine,  or  a  ten  per  cent,  solution  of  euphthalmine.  Second, 
in  iritis  and  irido-cyditis  to  give  rest  to  the  iris  and  to  prevent  the  de- 
velopment of  synechia  and  occlusion  of  the  pupil  area  with  exudates  ;  for 
this  purpose  it  is  the  best  of  the  mydriatics.  Third,  to  paralyze  accommo- 
dation when  it  is  desired  to  determine  with  accuracy  the  refraction  of 
the  eye  for  the  fitting  of  spectacles  and  other  purposes,  and  to  overcome 
spasm  of  accommodation  ;  in  such  cases  repeated  instillations  of  the  atro- 
pine  solution  may  be  necessary.  Fourth,  to  give  rest  to  the  eye,  to  exert 
an  anodyne  alterative  influence,  and  to  lessen  the  liability  to  iritis  in 
various  forms  of  keratitis  and  ulcers  of  the  cornea  ;  in  phlyctenular  kera- 
titis  it  is  especially  useful,  and  in  perforating  ulcers,  particularly  if  they 
have  a  central  situation,  it  overcomes  the  prolapse  of  the  iris  ;  for  this 
purpose  it  must  be  used  very  freely. 

The  existence  of  glaucoma,  or  any  tendency  to  it,  is  a  centra-indica- 
tion to  the  use  of  atropine.  It  may  in  chronic  glaucoma  precipitate  an 
acute  attack,  and  in  acute  glaucoma  causes  marked  increase  of  pain,  of 
congestion,  and  of  the  already  excessive  intra-ocular  tension. 

Belladonna  was  at  one  time  highly  commended  as  a  prophylactic 
against  scarlet  fever.  The  original  teaching  of  George  B.  Wood,  that  as 
such,  however,  it  has  no  value,  has  been  abundantly  confirmed  in  later 
times. 

TOXICOLOGY. — Sufficient  has  already  been  said  about  the  general 
symptoms  of  belladonna- poisoning.  Those  which  are  characteristic  are 
the  dryness  of  the  throat,  the  increased  frequency  of  breathing,  the 
dilated  pupils,  the  red  efflorescence  on  the  skin,  the  rapid  pulse,  the 
active  talkative  delirium,  sometimes  convulsions,  all  ending  in  abolition 
of  function,  as  shown  by  stupor,  rapid  feeble  pulse,  cold  extremities, 
and  paralysis.  Morel 41  calls  attention  to  a  sort  of  laryngitis  produced  by 
poisonous  doses  of  belladonna,  characterized  by  pain  in  the  larynx,  rough- 
ness of  voice,  and  the  expectoration  of  minute,  pearly,  tough  pellets.  It 
was  present  in  the  advanced  stages  of  two  cases  of  poisoning  under  his 
care.  Raphael "  has  noted  glycosuria  as  a  symptom  of  belladonna-poison- 
ing and  has  experimentally  produced  the  condition  with  atropine  in  rabbits. 

The  minimum  fatal  doses  of  the  preparations  of  belladonna  are  scarcely 
known. 


1 84  GENERAL  REMEDIES. 

An  enema  representing  eighty  grains  of  the  root  has  produced  death  in  five 
hours  ; i2  but,  on  the  other  hand,  recovery  has  occurred  after  the  ingestion  of  three 
drachms  of  the  extract.*  A  tenth,  or  even  a  twentieth,  of  a  grain  of  atropine  will 
often  produce  alarming  symptoms  ;  yet  Chambers 43  reports  recovery  in  a  child 
four  years  old  who  had  taken  about  two  teaspoonfuls  of  a  solution  containing  a 
grain  of  the  alkaloid  in  half  an  ounce,  and  Stracham  in  a  child  of  five  years  from  a 
tablespoonful  of  glycerin  containing  one-half  per  cent,  of  alkaloids. 

After  death  from  belladonna,  no  characteristic  lesions  are  to  be  found. 

In  the  treatment  of  belladonna-poisoning,  the  stomach  should  be 
emptied  by  means  of  emetics  or  the  stomach-pump,  and  tannic  acid  ex- 
hibited as  an  imperfect  antidote.  The  various  symptoms  must  then  be 
met  as  they  arise,  respiration  and  circulation  being  maintained  as  in  other 
narcotic  poisoning  ;  according  to  Reichert,  recovery  may  follow  after  a 
dose  much  larger  than  the  maximal  fatal  quantity  if  artificial  respiration 
be  persisted  in.  The  exact  value  of  opium  in  belladonna-poisoning  has 
not  been  determined,  and  its  employment  should  be  tentative,  although 
good  is  to  be  expected  from  its  judicious  use.  Physostigma  and  jabo- 
randi  appear  to  be  somewhat  antagonistic  to  atropine  within  certain 
limits,  and  jaborandi  has  been  used  in  atropine-poisoning.  (See  Calabar 
Bean  and  Jaborandi. )  After  toxic  doses  of  belladonna,  there  is  generally 
complete  retention  of  urine  ;  and  as  this  secretion  contains  the  greater 
part  of  the  ingested  poison,  and  as  reabsorption  from  the  bladder  is  at 
least  conceivable,  the  catheter  should  be  used  early. 

ADMINISTRATION. — Belladonna  is  never  used  internally  in  substance. 
All  the  preparations  of  the  U.  S.  Pharmacopoeia  except  two  (designated 
below)  are  made  from  the  leaves.  They  are  the  tincture  (TINCTURA 
BELLADONNA  FOLIORUM — ten  per  cent.,  U.  S. ),  dose,  ten  to  thirty 
minims  (0.6-1.9  C.c. );  the  alcoholic  extract  (EXTRACTUM  BELLADONNA 
FOLIORUM,  U.  S. ),  dose,  one-eighth  to  one-half  grain  (0.008-0.032  Gm. ); 
the  fluid  extract  of  the  root  (FLUIDEXTRACTUM  BELLADONNA  RADICIS, 
U.  S. ),  dose,  one  to  two  minims  (0.06—0.12  C.c.);  the  plaster  (EMPLAS- 
TRUM  BELLADONNA,  U.  S. )  contains  three  parts  of  extract  of  bella- 
donna leaves  to  seven  of  adhesive  plaster  ;  the  ointment  (UNGUENTUM 
BELLADONNA,  U.  S. )  contains  ten  per  cent,  of  extract.  The  liniment 
(LINIMENTUM  BELLADONNA,  U.  S.)  is  made  by  adding  five  per  cent, 
of  camphor  to  the  fluid  extract.  Atropine  sulphate  (ATROPIN^E  SUL- 
PHAS, U.  S. )  is  most  commonly  used,  on  account  of  its  solubility  in 
water.  Dose,  one-hundredth  to  one-sixtieth  of  a  grain  (0.00065-0.001 
Gm.),  increased  in  cases  of  poisoning.  In  dropping  an  atropine  solution 
in  the  eye  for  local  effect  the  head  should  be  so  inclined  that  the  fluid 
will  run  out  of  the  outer  canthus,  whilst  pressure  may  be  applied  upon 
the  optic  end  of  the  lachrymal  duct  to  prevent  passage  of  the  solution 
into  the  mouth.  Poisoning  through  the  local  use  of  the  remedy  by  oph- 
thalmic surgeons  has  often  occurred. 

*  Taylor's  Medical  Jurisprudence,  London,  1873,  432. 


DELIRIFACIENTS.  185 

STRAMONII  FOLIA.  U.  S.  Stramonium  Leaves. — The  leaves  of  the 
Datura  Stramonium.,  or  Jamestown  Weed,  are  recognized  by  the  U.  S. 
Pharmacopoeia,  but  have  passed  into  almost  complete  desuetude.  In  the 
numerous  cases  of  poisoning  which  have  been  produced  by  the  use  of  the 
plant  the  symptoms  have  been  precisely  those  of  belladonna-poisoning, 
and  the  treatment  is  the  same  in  the  two  poisonings.  The  alleged  active 
principle,  daturine,  is,  according  to  Ladenburg,  a  mixture  of  atropine 
and  hyoscyamine  ;  and  in  the  experimental  studies  of  Charles  Laurent,1 
the  physiological  effects  of  daturine  were  not  to  be  distinguished  from 
those  of  atropine.  The  preparations  of  stramonium  are  at  least  as  power- 
ful as  the  corresponding  preparations  of  belladonna,  but  are  rarely  used. 

Stramonium  leaves  have  been  very  widely  employed  in  the  form  of 
cigarettes,  or  a  powder,  to  be  smoked  in  a  pipe  or  otherwise  in  the  treat- 
ment of  spasmodic  asthma ;  also,  less  frequently,  as  a  narcotic  cataplasm 
for  inflamed  hemorrhoids.  In  either  case  some  care  is  necessary  to  avoid 
poisoning. 

The  dose  of  the  extract  (ExTRACTUM  STRAMONII,  U.  S. )  is  one- 
fourth  to  one-half  grain  (0.016-0.032  Gm. );  of  the  tincture  (TiNCTURA 
STRAMONII  SEMINIS — ten  per  cent.,  U.  S. ),  fifteen  to  thirty  minims 
(1-2  C.c. );  of  the  fluid  extract  (FLUIDEXTRACTUM  STRAMONII, 
U.  S. ),  one  to  two  minims  (0.06-0.12  C.c.).  The  ointment  (UNGUEN- 
TUM  STRAMONII,  U.  S. )  contains  ten  per  cent,  of  the  extract. 

HYOSCYAMUS.     U.  S. 

Hyoscyamus  niger  is  a  coarse  herbaceous  biennial,  indigenous  in 
England,  and  naturalized  in  the  Northern  United  States,  whose  leaves 
and  flowering  tops  of  the  second  year's  growth  are  official.  The  leaves 
are  large,  oblong-ovate,  deeply  sinuated,  and  very  hairy.  Hyoscyamus 
contains  two  alkaloids,  hyoscyamine  and  hyoscine.  Amorphous  hyoscy- 
amine of  commerce  is  a  mixture  of  hyoscyamine  and  hyoscine.  Hyoscine 
is  separated  from  it  as  a  syrupy  liquid  which  yields  crystallizable  salts. 

PHYSIOLOGICAL  ACTION. — The  clinical  experiments  of  Schroff,  Dul- 
lenberg,  Laurent,2  and  especially  of  Harley1  show  that  the  symptoms 
produced  by  large  doses  of  hyoscyamus  are  similar  to  those  caused  by 
belladonna,  excepting  that  there  is  a  greater  tendency  to  sleep  and  that 
the  delirium  is  less  furious.  The  assertion  of  Schroff,8  that  pneumonia 
is  in  the  rabbits  a  characteristic  lesion  of  hyoscyamus-poisoning,  is  nega- 
tived by  the  results  obtained  by  Lemattre  and  by  Laurent.  The  experi- 
ments of  Laurent  and  of  Heilmann4  are  in  accord  in  showing  that  hyoscy- 
amus acts  upon  the  circulation,  the  respiration,  the  neuro-muscular 
system,  and  the  intestines  very  similarly  to  belladonna. 

THERAPEUTICS. — Hyoscyamus  may  be  used  to  fulfil  any  of  the  indi- 
cations for  which  belladonna  is  employed.  Clinical  experience  appears 
in  a  measure  to  bear  out  the  assertions  of  various  authorities  as  to  the 
superiority  of  hyoscyamus  as  an  hypnotic.  It  has  been  much  employed 
as  a  calmative  and  hypnotic  by  alienists  in  various  forms  of  delirious 


i86  GENERAL  REMEDIES. 

insanity,   but  is  inferior  to  hyoscine.     The  diagnosis  and  treatment  oi 
hyoscyamus-poisoning  are  identical  with  those  of  belladonna-poisoning. 

The  preparations  are  the  extract  (EXTRACTUM  HYOSCYAMII,  U.  S.), 
dose,  one  to  three  grains  (0.06-0.19  Gm. )  ;  the  tincture  (TINCTURA 
HYOSCYAMI — ten  per  cent. ,  U.  S. ) ,  dose,  half  a  fluidrachm  to  two  flui- 
drachms  (2-8  C.c. )  ;  and  the  fluid  extract  (FLUIDEXTRACTUM  HYOS- 
CYAMI, U.  S. ),  dose,  five  minims  (0.3  C.c.). 

HYOSCYAMIN^E  SULPHAS.  U.  S. — Hyoscyamine  sulphate  is  a  whitish 
powder,  sometimes  indistinctly  crystalline,  very  soluble  in  water,  and 
having  a  bitter  taste.  According  to  J.  C.  Shaw,6  crystallized  hyoscyamine 
affects  the  system  of  voluntary  movement  and  the  circulation,  including 
the  heart  and  the  vaso-motor  system,  exactly  as  atropine  does.  In  a 
single  experiment  the  respiration  did  not  seem  to  be  affected  as  by  atro- 
pine ;  but  this  is  contradicted  by  results  arrived  at  by  previous  experi- 
menters, and  needs  confirmation.  Upon  man  Shaw  believes,  as  do  many 
other  alienists,  that  hyoscyamine  acts  as  a  soporific.  He  states  that  it  is 
less  powerful  as  a  mydriatic  than  is  atropine,  and  that  it  diminishes  the 
respiratory  rate.  It  must  be  remembered  that  these  studies  have  been 
made  upon  lunatics  ;  before  the  conclusions  can  be  accepted  as  estab- 
lished, much  more  elaborate  experimental  researches  are  necessary,  also 
studies  upon  normal  individuals,  and  especially  contrasting  studies  made 
with  atropine  and  hyoscyamine  upon  maniacs  ;  by  the  use  of  alternate 
doses  upon  the  same  individual  any  difference  of  action  of  the  two  drugs 
could  readily  be  detected.  It  should  also  be  remembered  that  in  his 
studies  of  hyoscyamine  upon  normal  men  Richter7  noted  no  tendency 
to  sleep.  In  a  careful  comparative  study  of  hyoscyamine  and  atropine 
upon  a  case  of  acute  mania  by  Sydney  Ringer,8  the  two  alkaloids  were 
found  to  act  practically  alike.  Commercial  hyoscyamine  was  formerly 
very  impure,  and  a  grain  has  been  given  with  impunity  ;  but  one-fortieth 
of  a  grain  of  the  pure  alkaloid  has  produced  violent  poisoning.9 

SCOPOLA.     U.  S. 

Under  this  name  the  U.  S.  Pharmacopoeia  recognizes  the  rhizomes  of 
the  Scopola  carniolica,  a  plant  which  is  common  in  the  hilly  districts  of 
Central  and  Southwestern  Europe.  The  Japanese  plant,  ,51  japonica,  is 
so  closely  allied  to  the  European  plant  that  many  botanists  have  doubted 
its  specific  distinctness,  and  the  rhizome  of  the  Japanese  species  appears 
to  be  identical  in  its  physiological  properties  with  that  of  S.  carniolica. 

Scopola  rhizomes  contain  hyoscyamine,  atropine,  and  scopolamine, 
with  perhaps  minute  quantities  of  other  alkaloids.  Of  these  alkaloids, 
hyoscyamine  appears  to  be  the  predominating  one,  but  scopolamine 
exists  in  considerable  quantity.  Scopolamine,  at  first  supposed  to  be  a 
distinct  alkaloid,  is  now  officially  recognized  as  identical  with  hyoscine. 

According  to  the  researches  of  Horatio  C.  Wood,  Jr.  ,*  the  crude  prepa- 
rations of  scopola  act  upon  cold-  and  warm-blooded  animals  precisely  as 


DELIRIFACIENTS.  187 

do  the  corresponding  preparations  of  belladonna,  but  the  chemistry  of  the 
subject  would  seem  to  indicate  that  scopola,  containing  hyoscine,  must 
have  more  somnifacient  influence  than  has  belladonna.  Further,  in  clin- 
ical studies  made  by  R.  W.  Wilcox2  it  was  found  that  when  scopola  is 
applied  externally  it  does  not  yield  its  alkaloid  to  absorption  as  does  bella- 
donna. In  the  manufacture  of  plasters  scopola  extract  has  been  largely 
used  as  a  substitute  for  belladonna  extract,  but  in  the  light  of  the  research 
of  Wilcox,  the  revisers  of  the  U.  S.  Pharmacopceia  of  1900  have  refused 
to  countenance  such  substitution,  and  the  only  crude  official  preparation 
of  scopola  is  the  fluid  extract  (FLUIDEXTRACTUM  SCOPOLA,  U.  S.). 
Dose,  one  or  two  minims  (0.06-0.1  C.c. ). 

HYOSCINE  HYDROBROMIDUM.  U.  S.  Hyoscine  Hydrobromide, 
Scopolamine  Hydrobromide. — Hyoscine  hydrobromate  occurs  in  minute, 
colorless,  rhombic  crystals,  which  are  freely  soluble  in  water  and  in 
alcohol. 

The  symptoms  which  are  produced  in  man  by  decided  doses  of  hy- 
oscine are  dryness  of  the  mouth,  flushing  of  the  face,  great  sleepiness, 
associated  in  some  cases  with  semi-delirious  mutterings,  and  a  feeling  of 
giddiness  like  that  of  intoxication.  The  respirations  are  lessened  in  fre- 
quency and  the  pulse-rate  is  usually  somewhat  diminished  ;  *  mydriasis  is 
usually,  but  not  always,  pronounced.  After  very  large  doses  the  symp- 
toms mentioned  are  more  intense  ;  the  pulse  becomes  slow  and  full,  but, 
according  to  the  sphygmographic  tracings  of  J.  B.  Andrews,  without 
alteration  of  tension,  the  pupils  dilated,  the  mouth  and  throat  excessively 
dry,  and  the  voice  hoarse  or  even  partially  suppressed,  probably  from 
paralysis  of  the  vocal  cords.  The  respirations  are  slow  and  full,  and  are 
said  by  H.  M.  Wetherill  to  be  sometimes  Cheyne- Stokes.  The  face  and 
the  general  surface  of  the  body  are  suffused,  muscular  relaxation  is  pro- 
nounced, and  loss  of  coordination  usually  very  evident.  The  skin,  so 
far  from  being  abnormally  dry,  is  commonly  bathed  in  perspiration. 
Several  observers  assert  also  that  there  is  a  rise  of  temperature.  Some- 
times the  delirium  is  active,  accompanied  by  visual  hallucinations,  and 
clonic  convulsions  with  opisthotonos  have  been  noted.  Mairet  and  Com- 
bemale11  found  that  monkeys  when  poisoned  by  it  gave  evidences  of  the 
presence  of  hallucinations,  such  as  are  sometimes  produced  in  man. 

PHYSIOLOGICAL  ACTION,  f  Circulation. — The  effect  of  hyoscine  upon 
the  circulation  is  slight ;  according  to  H.  C.  Wood,  small  doses  produce 
some  slowing  of  the  pulse  but  no  changes  in  the  pressure,  while  very 
large  doses  produce  a  slight  fall  in  pressure  due  to  depression  of  both 

«  It  has  been  noted  a  little  accelerated.  (Case,  Therap.  Gaz.,  1889,  J.  S.  Gibb.) 
t  The  fact  that  numerous  observers  had  asserted  that  the  impure  amorphous  hyoscya- 
mine  of  commerce  was  more  powerful  than  the  pure  crystallized  alkaloid  led  H.  C.  Wood, 
in  1884,  to  a  physiological  and  therapeutic  study  of  hyoscine,  which  led  to  the  use  of  the 
remedy  in  practical  medicine.  Other  physiological  studies  of  the  alkaloid  have  since 
been  made  by  Gley,  Rondeau,  Mairet  and  Combemale,  A.  Sohrt  (In.  Dis.  Dorpat,  1886), 


i88  GENERAL   REMEDIES. 

heart  and  vasomotor  centres.  Kochmann,12  however,  finds  that  small 
doses  produce  a  slight  rise  in  the  pressure  through  stimulation  of  the  vaso- 
motor centres,  and  that  the  fall  from  large  amounts  is  purely  cardiac.  He 
agrees  with  Wood  that  there  is  no  marked  change  in  the  pulse-rate  after  the 
use  of  small  doses,  but  he  obtained  after  large  doses  stimulation  of  the 
vagi  and  consequent  lessening  of  the  pulse-rate.  On  the  other  hand 
Robert  asserts,  that  the  alkaloid  acts  upon  the  peripheral  ends  of  the  car- 
diac inhibition  as  does  atropine,  producing  a  marked  increase  in  the  rate  of 
the  pulse.  Since,  however,  Claussens,13  Wood,  and  Kochmann  are  all  in 
agreement  that  no  dose  of  the  drug  produces  this  effect,  it  would  seem 
that  there  must  have  been  some  mistake  in  the  results  of  Kobert. 

Nervous  System. — All  the  authorities  quoted  are  in  agreement  that 
hyoscine  is  a  depressant  to  the  cerebrum.  Kochmann  found  that  the 
electrical  irritability  of  the  psychomotor  area  is  lessened  by  the  drug  and 
that  there  is  no  analgesia  during  the  sleep  it  produces.  According  to  H. 
C.  Wood,  it  is  a  depressant  to  the  motor  side  of  the  spinal  cord. 

Respiration. — According  to  both  Wood  and  Kochmann  hyoscine  acts 
as  a  depressant  to  the  respiration,  although  it  requires  comparatively  large 
doses  to  produce  any  marked  alteration  in  this  function.  In  fatal  poison- 
ing by  the  drug  death  is  always  due  to  asphyxia.  In  this  connection  it  is 
interesting  to  note  that  in  the  dog,  as  in  man,  it  is  almost  impossible  to 
kill  with  a  single  dose  of  hyoscine  ;  Kochmann  has  injected  as  much  as  o.  5 
Gm.  (7^  grains)  into  a  small  dog  intravenously  without  destroying  life. 

Secretions. — Upon  the  secretions  hyoscine  acts  much  like  atropine, 
producing  lessening  in  the  saliva,  and,  according  to  Kochmann,  also  in 
the  sweat  and  mucous  secretions.  In  cases  of  human  poisoning,  however, 
the  skin  is  usually  covered  with  moisture. 

Pupil. — Upon  the  pupil  hyoscine  acts  like  atropine,  a  half  of  one  per 
cent,  solution  rapidly  paralyzing  accommodation  and  dilating  the  pupil. 
It  is  said  that  it  does  not  produce  any  irritation,  and  that  its  maximum 
effects  are  reached  in  one-third  the  time  necessary  for  those  of  atropine, 
and  are  more  permanent  and  less  affected  by  eserine.  *  MM.  E.  Gley  and  P. 
Rondeau s  have  found  that  the  mydriasis  is  not  prevented  by  previous 
destruction  of  the  cervical  sympathetic  in  the  rabbit,  and  that  irritation 
of  the  sympathetic  nerve  will  increase  the  dilatation. 

SUMMARY. — The  dominant  physiological  action  of  hyoscine  is  upon 
the  cerebral  cortex,  producing  sleep  often  accompanied  by  a  low  de- 
lirium. It  is  also  a  centric  depressant  of  respiration,  and  depresses, 
though  somewhat  feebly,  the  whole  motor  cord :  upon  the  sexual  cen- 
tres it  acts  more  powerfully.  Its  influence  upon  the  circulation  is  very 
slight,  and  it  appears  to  exert  no  distinct  influence  on  the  nerves  or 

Claussens,  Kobert  (apparently  a  restatement  of  the  work  done  by  his  pupil  Sohrt),  and 
Kochmann.     The  results  described  by  Kobert  differ  so  markedly  as  to  render  it  probable 
that  he  had  either  a  different  or  an  impure  alkaloid.     The  experiments  of  H.  C.  Wood 
were  made  with  hyoscine  obtained  from  Merck. 
*  John  Tweedy,  Lancet,  Dec.  1886. 


DELIRIFACIENTS.  189 

muscles.  On  the  mucous  membrane  and  probably  on  the  muscles  of  the 
throat  it  acts  powerfully,  suppressing  secretion  and  interfering  with 
function. 

THERAPEUTICS. — Hyoscine  is  a  valuable  hypnotic  in  those  forms  of 
insomnia  in  which  sleep  is  banished  by  a  continual  flow  of  thoughts  or 
mental  images  passing  through  an  excited  brain  ;  hence  it  is  often  very 
effective  in  the  insomnia  of  delirium,  of  acute  mania,  or  of  other  forms 
of  insanity.  In  some  cases  of  insanity  with  cerebral  excitement  most 
excellent  results  are  produced  by  the  administration  every  three  to 
five  hours  of  small  doses  that  will  calm  without  causing  sleep.  As  an 
hypnotic  the  alkaloid  lends  itself  very  well  to  combinations,  intensi- 
fying greatly  the  influence  of  morphine,  chloral,  trional,  and  other  drugs 
of  the  class.  In  cases  of  severe  kidney  disease  it  would  seem  to  be  a 
safer  hypnotic  than  is  morphine,  and  as  it  has  no  sedative  influence  upon 
the  heart,  it  may  be  used  when  the  feeble  condition  of  that  viscus  forbids 
chloral. 

The  use  of  enormous  doses  (grain  one-fiftieth  to  one- twentieth)  of 
hyoscine  as  a  curative  remedy  in  acute  insanity  has  been  advocated  by 
H.  R.  Costons,  and  a  remarkable  case  is  recorded  by  Balagopal,*  in  which 
one-sixth  of  a  grain  was  given  hypodermically  to  a  patient  suffering  from 
violent,  acute  mania.  Immediately  after  the  injection  the  patient  fell, 
crying  that  he  was  dying  ;  his  face  became  deadly  pale,  the  conjunctiva 
insensitive,  the  breathing  difficult  and  stertorous,  the  limbs  spasmodically 
contracted.  After  recovery,  which  occurred  without  remedies  other  than 
hypodermic  injections  of  ether,  the  patient's  mental  condition  rapidly 
improved,  and  in  a  week  he  was  well. 

Probably  through  its  influence  upon  the  spinal  centres  hyoscine  is 
useful  in  all  cases  of  sexual  excitement,  such  as  nymphomania,  sperma- 
torrhoea, and  allied  affections.  It  is  the  most  certain  remedy  that  we 
have  in  ordinary  cases  of  over-frequent  seminal  emissions,  which  can 
usually  be  controlled  by  the  administration  of  the  one-hundred-and- 
twentieth  to  one-eightieth  of  a  grain  on  going  to  bed. 

As  an  analgesic  hyoscine  is  of  little  value,  though  Winnett5  states 
that  it  is  very  serviceable  in  the  crises  of  locomotor  ataxia.  It  has  been 
used  to  a  considerable  extent  in  certain  spasmodic  disorders.  Edlesen, 
as  early  as  1881,  affirmed  its  value  in  asthma  and  whooping-cough. 
Erb  has  used  it  with  advantage  in  various  spasms.  In  spinal  accessory 
spasm  it  has  in  our  hands  failed.  On  the  other  hand,  in  pronounced 
paralysis  agitans,  attended  by  much  aching  pain,  we  have  seen  it  give 
very  great  relief  from  both  pain  and  tremors.  Usually  in  these  cases  it 
should  be  administered  only  at  bedtime,  as  it  is  merely  a  palliative,  and 
if  used  continually  is  prone  to  lose  its  power. 

In  1900  Schneiderlin  suggested  the  hypodermic  injections  of  large 
doses  of  morphine  and  scopolamine  for  the  production  of  surgical  anes- 
thesia. In  this  method  doses  ranging  from  one-sixth  to  one-half  grain  of 
morphine  are  given  in  conjunction  with  from  one-hundredth  to  one-fiftieth 


i9o  GENERAL  REMEDIES. 

grain  of  hyoscine  are  injected  an  hour  before  the  operation.  The  idea 
was  founded  on  an  erroneous  conception  of  the  physiological  action  of 
hyoscine  which  is  in  no  proper  sense  the  antagonist  of  morphine  and  pos- 
sesses but  feeble  analgesic  properties.  H.  C.  Wood,  Jr.10  collected  the 
reports  of  nearly  2000  cases,  with  9  deaths,  giving  the  frightful  mortality 
of  i  :  221.  Moreover  in  69  per  cent,  of  the  cases  ether  or  chloroform  was 
required  to  produce  sufficient  anaesthesia  for  operation.  It  is  possible 
that  in  certain  classes  of  cases  the  method  may  occasionally  prove  of 
value,  but  as  a  routine  measure  it  cannot  be  too  strongly  condemned. 

TOXICOLOGY. — No  fatal  case  of  poisoning  by  hyoscine  is  on  record. 
H.  A.  Hutchinson6  took  a  quarter  of  a  grain  of  very  impure  hyoscine  : 
quiet  coma  with  entire  muscular  relaxation  was  produced,  and  lasted 
eleven  hours.  The  fiftieth  of  a  grain  has,  however,  several  times  caused 
very  alarming  symptoms,  and  much  smaller  doses  are  affirmed  to  have 
produced  serious  effects  (see  Carey7). 

O'  Hara  8  saw  one-ninety-sixth  of  a  grain  administered  hypodermically  produce 
very  severe  disturbance,  lasting  for  twenty-eight  hours,  with  total  lack  of  remem- 
brance of  occurrences  which  took  place  during  the  seven  hours  following  the  in- 
jection ;  while  Root9  asserts  that  one-three-hundredth  of  a  grain  given  by  the 
mouth  produced  violent  poisoning,  and  even  one-twelve-hundredth  very  pro- 
nounced symptoms.  The  dispensing  of  such  minute  quantities  of  a  drug  is  so  diffi- 
cult that  it  is  probable  that  more  of  the  alkaloid  was  given  than  is  alleged. 

ADMINISTRATION. — Hyoscine  very  rarely  if  ever  causes  other  dis- 
agreeable after-effects  than  dryness  of  the  throat,  although  occasionally 
some  headache  has  been  noted.  The  action  of  hyoscine  given  hypoder- 
mically is  manifested  inside  of  ten  minutes,  and  lasts  from  six  to  eight 
hours.  In  severe  excitement,  especially  that  of  violent  insanity,  the  dose 
should  be  repeated  every  six  or  eight  hours.  The  dose  for  hypodermic 
use  is  from  the  one-hundred-and-fiftieth  to  one-eightieth  of  a  grain  (o.  6— 
0.8  milligramme).  Excessive  susceptibility  to  the  action  of  hyoscine  being 
a  not  infrequent  idiosyncrasy,  it  is  best  to  give  at  first  amounts  below  the 
minimum  dose  here  stated.  The  tastelessness  of  hyoscine  makes  it  easy 
to  administer  to  insane  or  other  patients  without  their  knowledge. 

Owing  to  its  great  influence  upon  the  throat,  hyoscine  is  strongly 
contra-indicated  in  cases  of  acute  disease  of  the  throat  sufficiently  violent 
to  interfere  with  deglutition  or  respiration.  Thus,  we  have  seen  it,  when 
given  in  violent  anginose  scarlatina  with  delirium,  cause  such  rapid 
increase  in  the  difficulty  of  respiration  as  to  suggest  that  it  played  an 
important  role  in  the  production  of  the  fatal  asphyxia. 

HOMATROPIN^G  HvDROBROMiDUM.  U.  S.  Homatropine  Hydrobro- 
mide. — Homatropine  is  an  alkaloid  artificially  produced  from  atropine, 
the  hydrobromate  of  which  is  preferred  for  practical  use  on  account  of  its 
being  stable  and  not  hygroscopic.  It  is  said  to  cause,  when  taken  inter- 
nally, symptoms  similar  to  those  caused  by  atropine,  except  in  regard  to 
the  circulation.  The  retardation  of  the  pulse  has  been  proved  by  Tweedy 


DELIRIFACIENTS.  191 

and  Ringer,  Beyer,  and  De  Schweinitz  and  Hare l  to  be,  at  least  in  part, 
the  result  of  a  direct  action  of  the  drug  upon  the  heart-muscle  or  its  con- 
tained ganglia,  since  in  the  frog  and  in  the  terrapin  the  application  of 
homatropine  hydrobromate  to  the  exposed  heart  in  situ  reduces  very 
greatly  the  number  of  the  beats.  In  the  dog  injection  of  the  alkaloid  into 
the  jugular  vein  is  followed  by  a  fall  of  as  much  as  thirty  or  forty  beats 
per  minute,  which  De  Schweinitz  and  Hare  believe  to  be  in  part  due  to 
stimulation  of  the  vagi  nerves,  because  section  of  the  vagi  causes  a  marked 
increase  in  the  pulse-rate,  ' '  although  not  such  a  rise  as  would  appear  if 
the  inhibitory  apparatus  was  intact."  De  Schweinitz  and  Hare  found 
that  the  fall  of  the  pulse-rate  was  accompanied  by  a  marked  fall  of  the  ar- 
terial pressure.  Since  the  production  of  asphyxia  was  followed  at  this 
time  by  a  pronounced  rise  in  the  arterial  pressure,  it  would  appear  that 
the  fall  of  pressure  is  not  the  result  of  a  vaso-motor  paralysis,  but  of  the 
cardiac  influence  of  the  drug. 

It  has  been  shown  by  the  experiments  of  Tweedy  and  Ringer,  con- 
firmed by  De  Schweinitz  and  Hare,  that  homatropine  produces  in  the 
frog  a  brief  period  of  tetanus,  followed  by  absolute  muscular  relaxation, 
with  abolition  of  reflex  and  voluntary  activity,  followed  in  from  six  to 
eight  hours,  if  the  dose  has  been  properly  proportioned,  by  return  of  vol- 
untary movements,  associated  with  tetanic  spasms  of  great  intensity. 
The  convulsive  movements  and  the  paralysis  are,  according  to  De 
Schweinitz  and  Hare,  of  spinal  origin,  as  the  nerve-trunks  and  muscles 
are  not  affected.  The  cause  of  death  is  centric  respiratory  paralysis. 

The  influence  of  the  alkaloid  upon  the  eye  is  practically  identical  with 
that  of  atropine,  except  that  it  is  somewhat  more  feeble  and  is  much  more 
temporary.  The  pupil  begins  to  dilate  in  from  seven  to  twenty  minutes 
after  the  instillation  of  the  drug,  and  accommodation  fails  in  from  forty  to 
ninety  minutes  ;  in  from  one  to  seventy-two  hours  the  recovery  is  com- 
plete. According  to  De  Schweinitz,  a  solution  of  one  in  eighty  is  suf- 
ficiently strong  to  paralyze  accommodation  completely,  provided  it  be 
dropped  repeatedly  into  the  eye.  When  it  is  desired  simply  to  dilate 
the  pupil  for  ophthalmoscopic  examinations,  a  single  application  of  a 
solution  of  four  grains  to  the  ounce  suffices.  Homatropine  as  a  practical 
mydriatic  has  the  advantage  of  fugaciousness  of  action,  of  being  not  at  all 
irritant,  and  of  being  little  prone  to  produce  systemic  disturbance. 

CANNABIS   INDICT— INDIAN    CANNABIS.     U.  S. 

The  alcoholic  extract  of  Indian  hemp  is  a  blackish,  resinous  extract, 
of  a  decided  narcotic  odor  and  a  peculiar  taste.  In  the  East  hemp  and 
its  educts  are  used  as  narcotic  stimulants.  Gunjah  is  the  dried  plant  as 
sold  in  the  bazaars  of  Calcutta  for  smoking.  Churrhus,  known  in  Egypt 
as  hashish,  is  the  resinous  exudation  with  the  epidermis,  etc. ,  scraped  off 
the  leaves. 

Various  substances  have  been  announced  as  the  active  principle  of 
cannabis  indica, — cannabin,  cannabinon,  tetano-cannabene,  oxycannabin, 


i92  GENERAL  REMEDIES. 

cannabene,  etc.  Cannabinol  of  Wood,  Spivey,  and  Easterfield  is,  ac- 
cording to  Fraenkel,5  inert,  and  should  be  known  as  psuedocannabinol, 
the  name  cannabinol  being  retained  for  a  distinct  substance  which  he, 
Fraenkel,  has  isolated  and  found  to  be  active. 

PHYSIOLOGICAL  ACTION. — When  given  in  full  doses,  cannabis  indica 
produces  a  feeling  of  exhilaration,  with  a  condition  of  revery,  and  a 
train  of  mental  and  nervous  phenomena  which  varies  very  much  ac- 
cording to  the  temperament  or  idiosyncrasies  of  the  subject,  and  very 
probably  also,  to  some  extent,  according  to  the  nature  of  his  surround- 
ings. The  sensations  are  generally  spoken  of  as  very  pleasurable  ; 
often  beautiful  visions  float  before  the  eyes,  and  a  sense  of  ecstasy  fills 
the  whole  being  ;  sometimes  the  venereal  appetites  are  greatly  excited  ; 
sometimes  loud  laughter,  constant  giggling,  and  other  indications  of 
mirth  are  present.  Some  years  since,  in  experimenting  with  an  extract 
made  from  the  American  plant,  H.  C.  Wood  took  a  large  dose,  and  de- 
scribed the  result  as  follows  :  * 

"About  half-past  four  P.M.,  September  23,  I  took  most  of  the  extract.  No 
immediate  symptoms  were  produced.  About  seven  P.M.  a  professional  call  was 
requested,  and,  forgetting  all  about  the  hemp,  I  went  out  and  saw  my  patient 
While  writing  the  prescription,  I  became  perfectly  oblivious  to  surrounding  ob- 
jects, but  went  on  writing,  without  any  check  to  or  deviation  from  the  ordi- 
nary series  of  mental  acts  connected  with  the  process,  at  least  that  I  am  aware  of. 
When  the  recipe  was  finished,  I  suddenly  recollected  where  I  was,  and,  looking 
up,  saw  my  patient  sitting  quietly  before  me.  The  conviction  was  irresistible  that 
I  had  sat  thus  many  minutes,  perhaps  hours,  and  directly  the  idea  fastened  itself 
that  the  hemp  had  commenced  to  act,  and  had  thrown  me  into  a  trance-like  state 
of  considerable  duration,  during  which  I  had  been  stupidly  sitting  before  my  won- 
dering patient.  I  hastily  arose  and  apologized  for  remaining  so  long,  but  was  as- 
sured I  had  only  been  a  very  few  minutes.  About  seven  and  a  half  P.M.  I  returned 
home.  I  was  by  this  time  quite  excited,  and  the  feeling  of  hilarity  now  rapidly  in- 
creased. It  was  not  a  sensuous  feeling,  in  the  ordinary  meaning  of  the  term  ;  it 
was  not  merely  an  intellectual  excitation ;  it  was  a  sort  of  bien-ttre, — the  very 
opposite  to  malaise.  It  did  not  come  from  without ;  it  was  not  connected  with  any 
passion  or  sense.  It  was  simply  a  feeling  of  inner  joyousness  ;  the  heart  seemed 
buoyant  beyond  all  trouble ;  the  whole  system  felt  as  though  all  sense  of  fatigue 
were  forever  banished  ;  the  mind  gladly  ran  riot,  free  constantly  to  leap  from  one 
idea  to  another,  apparently  unbound  from  its  ordinary  laws.  I  was  disposed  to 
laugh  ;  to  make  comic  gestures  ;  one  very  frequently  recurrent  fancy  was  to  imi- 
tate with  the  arms  the  motions  of  a  fiddler,  and  with  the  lips  the  tune  he  was  sup- 
posed to  be  playing.  There  was  nothing  like  wild  delirium,  nor  any  hallucinations 
that  I  remember.  At  no  time  had  I  any  visions,  or  at  least  any  that  I  can  now  call 
to  mind  ;  but  a  person  who  was  with  me  at  that  time  states  that  once  I  raised  my 
head  and  exclaimed,  '  Oh,  the  mountains  !  the  mountains  !'  While  I  was  perform- 
ing the  various  antics  already  alluded  to,  I  knew  very  well  I  was  acting  exceedingly 
foolishly,  but  could  not  control  myself.  I  think  it  was  about  eight  o'clock  when  I 
began  to  have  a  feeling  of  numbness  in  my  limbs,  also  a  sense  of  general  uneasi- 
ness and  unrest,  and  a  fear  lest  I  had  taken  an  overdose.  I  now  constantly  walked 
about  the  house  ;  my  skin  to  myself  was  warm,  in  fact  my  whole  surface  felt  flushed  ; 
my  mouth  and  throat  were  very  dry  ;  my  legs  put  on  a  strange,  foreign  feeling,  as 
though  they  were  not  a  part  of  my  body.  I  counted  my  pulse  and  found  it  one 
hundred  and  twenty,  quite  full  and  strong.  A  foreboding,  an  undefined,  horrible 
fear,  as  of  impending  death,  now  commenced  to  creep  over  me  ;  in  haste  I  sent  for 


DELIRIFACIENTS.  193 

medical  aid.  The  curious  sensations  in  my  limbs  increased.  My  legs  felt  as  though 
they  were  waxen  pillars  beneath  me.  I  remember  feeling  them  with  my  hand  and 
finding  them,  as  I  thought  at  least,  very  firm,  the  muscles  all  in  a  state  of  tonic  con- 
traction. About  eight  o'clock  I  began  to  have  marked  '  spells,' — periods  when  all 
connection  seemed  to  be  severed  between  the  external  world  and  myself.  I  might 
be  said  to  have  been  unconscious  during  these  times,  in  so  far  that  I  was  oblivious 
to  all  external  objects,  but  on  coming  out  of  one  it  was  not  a  blank,  dreamless  void 
upon  which  I  looked  back,  a  mere  empty  space,  but  rather  a  period  of  active  but 
aimless  life.  I  do  not  think  there  was  any  connected  thought  in  them  ;  they  appeared 
to  be  simply  wild  reveries,  without  any  binding  cord, — each  a  mere  chaos  of  dis- 
jointed ideas.  The  mind  seemed  freed  from  all  its  ordinary  laws  of  association,  so 
that  it  passed  from  idea  to  idea,  as  it  were,  perfectly  at  random.  The  duration  of 
these  spells  to  me  was  very  great,  although  they  really  lasted  but  from  a  few  seconds 
to  a  minute  or  two.  Indeed,  I  now  entirely  lost  my  power  of  measuring  time. 
Seconds  were  hours  ;  minutes  were  days  ;  hours  were  infinite.  Still,  I  was  perfectly 
conscious  during  the  intermissions  between  the  paroxysms.  I  would  look  at  my 
watch,  and  then  after  an  hour  or  two,  as  I  thought,  would  look  again  and  find  that 
scarcely  five  minutes  had  elapsed.  I  would  gaze  at  its  face  in  deep  disgust,  the 
minute-hand  seemingly  motionless,  as  though  graven  in  the  face  itself  ;  the  laggard 
second-hand  moving  slowly,  so  slowly.  It  appeared  a  hopeless  task  to  watch  during 
its  whole  infinite  round  of  a  minute,  and  always  would  I  give  up  in  despair  before  the 
sixty  seconds  had  elapsed.  Occasionally,  when  my  mind  was  most  lucid,  there  was 
in  it  a  sort  of  duplex  action  in  regard  to  the  duration  of  time.  I  would  think  to 
myself,  It  has  been  so  long  since  a  certain  event, — an  hour,  for  example,  since  the 
doctor  came  ;  and  then  reason  would  say,  No,  it  has  been  only  a  few  minutes  ;  your 
thoughts  or  feelings  are  caused  by  the  hemp.  Nevertheless,  I  was  not  able  to  shake 
off  this  sense  of  the  almost  indefinite  prolongation  of  time,  even  for  a  minute.  The 
paroxysms  already  alluded  to  were  not  accompanied  by  muscular  relaxation. 
About  a  quarter  before  nine  o'clock,  I  was  standing  at  the  door,  anxiously  watching 
for  the  doctor,  and  when  the  spells  would  come  on  I  would  remain  standing,  lean- 
ing slightly,  perhaps,  against  the  door-way.  After  a  while  I  saw  a  man  approach- 
ing, whom  I  took  to  be  the  doctor.  The  sounds  of  his  steps  told  me  he  was  walking 
very  rapidly,  and  he  was  under  a  gas-lamp,  not  more  than  one-fourth  of  a  square 
distant,  yet  he  appeared  a  vast  distance  away,  and  a  corresponding  time  approach- 
ing. This  was  the  only  occasion  on  which  I  noticed  an  exaggeration  of  distance  ; 
in  the  room  it  was  not  perceptible.  My  extremities  now  began  to  grow  cold,  and  I 
went  into  the  house.  I  do  not  remember  further,  until  I  was  aroused  by  the  doctor 
shaking  or  calling  me.  Then  intellection  seemed  pretty  good.  I  narrated  what  I 
had  done  and  suffered,  and  told  the  doctor  my  opinion  was  that  an  emetic  was  indi- 
cated, both  to  remove  any  of  the  extract  still  remaining  in  my  stomach,  and  also  to 
arouse  the  nervous  system.  I  further  suggested  our  going  into  the  office,  as  more 
suitable  than  the  parlor,  where  we  then  were.  There  was  at  this  time  a  very  marked 
sense  of  numbness  in  my  limbs,  and  what  the  doctor  said  was  a  hard  pinch  pro- 
duced no  pain.  When  I  attempted  to  walk  up-stairs,  my  legs  seemed  as  though 
their  lower  halves  were  made  of  lead.  After  this  there  were  no  new  symptoms, 
only  an  intensifying  of  those  already  mentioned.  The  periods  of  unconsciousness 
became  at  once  longer  and  more  frequent,  and  during  their  absence  intellection  was 
more  imperfect,  although  when  thoroughly  roused  I  thought  I  reasoned  and  judged 
clearly.  The  oppressive  feeling  of  impending  death  became  more  intense.  It  was 
horrible.  Each  paroxysm  would  seem  to  have  been  the  longest  I  had  suffered  ;  as 
I  came  out  of  it,  a  voice  seemed  constantly  saying,  '  You  are  getting  worse  ;  your 
paroxysms  are  growing  longer  and  deeper ;  they  will  overmaster  you ;  you  will 
die.'  A  sense  of  personal  antagonism  between  my  will-power  and  myself,  as 
affected  by  the  drug,  grew  very  strong.  I  felt  as  though  my  only  chance  was  to 
struggle  against  these  paroxysms,— that  I  must  constantly  arouse  myself  by  an  effort 
of  will ;  and  that  effort  was  made  with  infinite  toil  and  pain.  I  felt  as  if  some  evil 

13 


i94  GENERAL  REMEDIES. 

spirit  had  control  of  the  whole  of  me  except  the  will-power,  and  was  in  determined 
conflict  with  that,  the  last  citadel  of  my  being.  I  have  never  experienced  anything 
like  the  fearful  sense  of  almost  hopeless  anguish  and  utter  weariness  which  was 
upon  me.  Once  or  twice  during  a  paroxysm  I  had  what  might  be  called  nightmare 
sensations  :  I  felt  myself  mounting  upward,  expanding,  dilating,  dissolving  into  the 
wide  confines  of  space,  overwhelmed  by  a  horrible,  rending,  unutterable  despair. 
Then,  with  tremendous  effort,  I  seemed  to  shake  this  off,  and  to  start  up  with  the 
shuddering  thought,  Next  time  you  will  not  be  able  to  throw  this  off,  and  what 
then  ?  Under  the  influence  of  an  emetic  I  vomited  freely,  without  nausea,  and  with- 
out much  relief.  About  midnight,  at  the  suggestion  of  the  doctors,  I  went  up-stairs 
to  bed.  My  legs  and  feet  seemed  so  heavy  I  could  scarcely  move  them,  and  it  was 
as  much  as  I  could  do  to  walk  with  help.  I  have  no  recollection  whatever  of  being 
undressed,  but  am  told  I  went  immediately  to  sleep.  When  I  awoke,  early  in  the 
morning,  my  mind  was  at  first  clear,  but  in  a  few  minutes  the  paroxysms,  similar  to 
those  of  the  evening,  came  on  again,  and  recurred  at  more  or  less  brief  intervals 
until  late  in  the  afternoon.  All  of  the  day  there  was  marked  anaesthesia  of  the  skin. 
At  no  time  were  there  any  aphrodisiac  feelings  produced..  There  was  a  pro- 
nounced increase  of  the  urinary  secretion.  There  were  no  after-effects,  such  as 
nausea,  headache,  or  constipation  of  the  bowels." 

The  sense  of  prolongation  of  time  present  in  most  cases  of  hemp 
intoxication  is  evidently  due  to  the  immense  rapidity  of  the  succession  of 
ideas.  The  mind  measures  time  by  the  duration  of  its  own  processes, 
and  when  an  infinitude  of  ideas  arise  before  it  in  the  time  usually  occu- 
pied by  a  few,  time  becomes  infinitely  prolonged  to  the  mind.  It  is  a  life- 
time in  the  minute.  A  very  common  mental  phenomenon,  not  easily 
explained  unless  as  a  result  of  disassociation  of  the  cerebral  hemispheres, 
is  a  condition  of  double  consciousness,  a  sense  of  having  two  existences, 
of  being  at  the  same  time  one's  self  and  somebody  else. 

In  some  cases  Indian  hemp  produces,  in  addition  to  or  even  in  the 
place  of  the  symptom  already  spoken  of,  marked  disturbances  of  motility. 
Convulsions  have  been  noticed  by  Lawrie,2  and  local  spasms,  with  salaam 
convulsions,  by  F.  H.  Brown.  According  to  O'  Shaughnessy,  the  induc- 
tion of  catalepsy  is  not  rare  among  the  Hindoos. 

Whatever  may  be  the  symptoms  of  the  first  stage,  sooner  or  later,  if 
the  dose  be  sufficient,  drowsiness  comes  on.  Generally,  before  it  is 
marked,  partial  anaesthesia,  often  with  partial  loss  of  strength,  is  mani- 
fested, especially  in  the  lower  limbs.  The  pupils  are  dilated,  the  pulse 
is  quickened,  and  finally  the  subject  falls  into  a  heavy  sleep,  out  of  which 
he  generally  awakes  hungry,  without  any  of  the  wretched  gastric  sensa- 
tions or  the  malaise  felt  after  an  opiate.  Confusion  of  thought,  however, 
may  persist  for  some  hours.  Cannabis  exerts  no  constipating  influence 
upon  the  bowels,  and  appears  to  increase,  rather  than  decrease,  the  excre- 
tion of  the  kidneys. 

In  the  dog,  hemp  extract  causes  exaltation  followed  by  profound  sleep 
(Hans  Zeitler,3  H.  A.  Hare4).  That  the  drug  has  very  little  influence 
upon  the  vital  functions  is  shown  by  the  enormous  amounts  required  to 
kill.  Hare  noted  both  in  the  dog  and  in  the  frog  heightened,  followed 
by  markedly  lessened,  reflex  activity.  The  loss  of  reflex  activity  was 


DELIRIFACIENTS.  195 

the  result  of  an  influence  exerted  upon  the  sensory  side  of  the  cord  or 
upon  the  sensory  nerve-trunk,  the  anaesthesia  in  the  frog  being  complete 
at  a  time  when  voluntary  movement  was  preserved  ;  further,  when  the 
drug  was  applied  directly  to  the  nerve-trunk  it  produced  sensory  palsy. 
Although  probably  a  local  anaesthetic,  cannabis  indica  is  too  irritant  to 
be  applied  to  delicate  mucous  membranes. 

THERAPEUTICS. — Hemp  has  been  used  in  this  country  chiefly  for  the 
relief  of  pain ,  but  also  to  some  extent  as  an  hypnotic.  As  an  analgesic, 
it  is  very  much  inferior  to  opium,  but  may  be  tried  when  the  latter  is 
for  any  reason  contra-indicated.  In  full  doses,  in  neuralgic  pains,  it 
certainly  often  gives  relief.  It  has  been  very  largely  employed  to  induce 
euthanasia  in  the  advanced  stages  of  phthisis,  and  constitutes,  it  is  said,  a 
popular  nostrum  employed  for  that  purpose.  In  tetanus,  Indian  hemp 
has  been  used  quite  largely,  and  is  sometimes  apparently  an  aid  to  other 
remedies  ;  it  should  be  given  to  intoxication.  As  first  suggested  by 
Seguin,  hemp  extract,  administered  for  months  continuously  in  such 
doses  as  will  keep  just  within  the  limit  of  distinct  physiological  effects, 
is  often  effective  in  migraine. 

ADMINISTRATION. — Extract  of  hemp  is  a  very  unsatisfactory  drug 
from  the  fact  that  one-eighth  of  a  grain  of  one  extract  will  produce  de- 
cided intoxication,  and  many  grains  can  be  taken  of  another  extract  that 
cannot  be  distinguished  physically  or  chemically  from  the  first  specimen. 
The  only  way  of  using  it  with  advantage  is  for  the  practitioner  to  try 
various  samples  in  ascending  doses,  and  use  those  which  are  active  in  the 
dose  which  he  has  found  to  be  effective.  The  foreign  extracts  are,  on  the 
whole,  more  reliable  than  those  made  in  America.  It  should  always  be 
borne  in  mind  that,  though  the  symptoms  may  seem  alarming,  there  is 
much  less  danger  in  intoxication  from  hemp  than  from  alcohol.  No 
cases  of  fatal  poisoning  have  been  recorded.  The  dose  of  the  official 
tincture  (TINCTURA  CANNABIS  INDICES — ten  per  cent.,  U.  S. )  is  thirty 
minims  (2  C.c. )  ;  of  the  fluid  extract  (FLUIDEXTRACTUM  CANNABIS  IN- 
DICT, U.  S. ),  one  minim  (o.  12  C.c.)  ;  of  the  extract  (EXTRACTUM  CAN- 
NABIS INDIC^E,  U.  S. ),  one-sixth  to  one-fourth  of  a  grain  (0.01-0.016 
Gm. )  :  all  of  these  doses  may  be  indefinitely  increased  until  symptoms 
are  produced.  Notwithstanding  the  assertions  of  Fronmiiller  and  Hiller, 
the  tannate  of  cannabene  of  Merck  has  in  our  trials  of  it  seemed  to  be  inert. 

COCA.     U.  S. 

The  leaves  of  Erythroxylon  Coca,  a  South  American  shrub,  which 
is  very  largely  cultivated  in  Peru  and  neighboring  countries,  resemble 
in  size  and  shape  those  of  tea,  but  are  not  dentate,  and  are  distin- 
guished from  most  medicinal  leaves  by  a  slightly  curved  line,  running 
from  the  base  to  the  apex,  on  each  side  of  the  midrib,  and  produced 
by  the  peculiar  folding  of  the  leaf  in  the  bud.  In  1855  Gardeke  dis- 
covered in  coca  an  alkaloid  to  which  he  gave  the  name  Erythroxyline  ; 
but  this  principle  was  first  thoroughly  studied  by  Albert  Niemann,  from 


196  GENERAL  REMEDIES. 

whom  it  received  the  name  Cocaine,  by  which  it  is  now  usually  known. 
It  occurs  in  colorless,  transparent  prisms,  soluble  in  seven  hundred  and 
four  parts  of  cold  water,  and  forms  with  the  acids  very  bitter,  soluble, 
crystallizable  salts  ;  besides  cocaine,  the  leaves  contain  a  peculiar  tannin, 
known  as  coca-tannic  acid. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Locally  applied,  cocaine 
acts  as  a  very  distinct  and  certain  anaesthetic,  as  was  noted  by  Moreno  y 
Maiz  in  1862,  and  by  Von  Anrep  in  1880,  although  it  was  not  until  Sep- 
tember, 1884,  that  Karl  Roller1  demonstrated  the  practical  value  of  the 
drug.  According  to  the  observations  of  Von  Anrep,  the  nerves  of  special 
sense  are  as  readily  affected  as  are  those  of  common  sensibility  :  thus,  co- 
caine placed  upon  the  tongue  abolishes  at  the  place  of  contact,  for  the  time 
being,  the  sense  of  taste.  At  the  point  of  contact  there  is  at  first  marked 
pallor,  but  after  a  short  time  very  pronounced  redness.  In  sensitive 
membranes  like  the  conjunctiva,  cocaine  also  causes  at  first  much  pain. 
The  primary  pallor  is  alleged  to  be  due  to  a  very  powerful  constriction 
of  the  small  blood-vessels,  and  has  led  F.  H.  Bosworth 2  to  the  conclusion 
that  cocaine  produces  rigid  contraction  in  unstriped  muscular  fibres  when- 
ever it  comes  in  contact  with  them.  The  anaesthesia  is  not,  however,  due 
to  any  spasm  of  the  vessels,  but  to  a  direct  action  upon  the  nerve-trunk. 
Applied  to  the  bared  nerve,  cocaine  paralyzes  first  the  sensitive  and 
afterwards  the  motor  fibres  (Feinberg5).  Arloing4  asserts  that  the  con- 
centrated solution  of  cocaine  placed  on  the  bared  nerve  produces  a  dis- 
tinct organic  change  in  the  nerve. 

According  to  the  experiments  of  Peter  Albertoni5  and  of  B.  Dan- 
ilewsky,6  cocaine  in  sufficient  concentration  acts  upon  all  forms  of  proto- 
plasm, first  exciting  and  then  paralyzing  functional  activity. 

Absorption  and  Elimination. — The  soluble  salts  of  cocaine  are  ab- 
sorbed with  great  rapidity.  They  have  the  power  of  passing  with  almost 
equal  ease  through  all  mucous  membranes,  so  that  their  absorption  is 
almost  immediate  when  they  are  employed  locally  in  the  nose,  urethra, 
or  other  part ;  hence  the  large  number  of  serious  poisonings  which  have 
resulted  from  their  local  use.  The  ultimate  fate  of  cocaine  in  the  body  is 
at  present  somewhat  uncertain.  It  appears  to  escape  to  some  extent 
through  the  urine  unchanged  (Thomas  Moreno  y  Maiz7 and  others),  but 
the  amount  that  has  been  recovered  by  chemists  has  been  so  small  (five 
per  cent.,  Wiechowski 42)  as  to  lead  to  the  wide-spread  belief  that  the 
alkaloid  is  in  great  part  destroyed  in  the  system  ;  and  Glasenap 4S  believes 
that  he  has  found  ecgonin,  a  decomposition  product,  in  the  urine. 

General  Action. — From  the  days  of  the  Incas  the  leaves  of  the  coca 
plant  have  been  enormously  used  by  the  natives  of  Western  South 
America  as  a  stimulant,  and  it  is  stated  that  about  forty  million  pounds 
of  them  are  annually  harvested.  Mixed  with  ashes  or  a  little  lime, 
they  are  chewed,  and  are  said  to  increase  greatly  for  the  time  being 
the  muscular  strength  and  endurance.  Although  coca  is  thus  employed 
habitually,  no  scientific  observers  have  given  detailed  reports  of  the 


DELIRIFACIENTS.  197 

symptoms  which  it  causes  in  the  South  American  natives,  observers  con- 
tenting themselves  with  the  mere  statement  that  the  physical  and  mental 
powers  of  the  natives  are  greatly  stimulated  by  the  drug.  Moderate 
doses  appear  to  increase  temporarily,  to  a  very  extraordinary  degree, 
both  physical  and  mental  power.  Various  travellers  concur  in  praising 
the  peculiar  sense  of  calm  and  happiness,  the  insensibility  to  fatigue, 
and  the  increase  of  bodily  and  mental  activity  which  the  drug  produces. 
Montegazza  states  that  when  he  took  two  hundred  grains  of  the  leaves 
he  was  in  a  short  time  plunged  into  a  condition  of  peculiar  delirious  beati- 
tude, in  which  he  seemed  to  be  isolated  from  the  rest  of  the  world 
and  to  live  in  a  peculiar  atmosphere  of  active  calm.  In  a  little  while 
there  came  also  a  sense  of  plenitude  of  power  which  was  accompanied  by 
a  real  increase  of  physical  ability,  so  that  gymnastics  which  in  his  ordi- 
nary condition  were  impossible  to  him  became  easy.  This  state  was  suc- 
ceeded by  a  natural  profound  sleep,  lasting  sometimes  for  twenty-four 
hours. 

Thus,  on  one  occasion  Montegazza  took  thirty-five  grammes,  and  an  hour  later 
nine  grammes,  etc.,  until  he  had  taken  in  the  course  of  two  hours  sixty  grammes  in 
all.  The  heart,  which  after  the  earliest  dose  had  been  slow  in  its  action,  directly 
after  the  second  dose  suddenly  became  rapid  and  very  violent  in  its  beats ;  but 
at  the  end  of  the  two  hours  the  palpitations  had  ceased,  although  the  pulse  was 
still  128  per  minute.  There  was  now  a  condition  of  intoxication  similar  to  that 
which  is  produced  by  hashish.  Montegazza  was  possessed  by  a  feeling  of  intense 
beatitude  and  inner  joyousness,  while  a  succession  of  visions  and  phantasma- 
goria, most  brilliant  in  color  and  form,  trooped  rapidly  before  his  eyes.  He 
seemed  to  himself  to  look  upon  a  world  of  shifting  and  incessant  activity,  as  into 
a  kaleidoscope.  He  rapidly  passed  into  a  delirious  condition,  in  which  he  ap- 
peared to  himself  to  be  unconscious,  although  when  addressed  he  would  answer 
rationally.  To  his  own  consciousness  he  was,  as  it  were,  buried  in  a  revery,  or 
perhaps  a  more  accurate  description  would  be  to  say  that  he  felt  as  though,  by  a 
sudden  rush  of  intellectual  and  emotional  life,  he  was  carried  out  of  himself,  and 
knew  not  whether  he  was  in  or  out  of  the  body.  An  hour  or  two  later  he  was  suffi- 
ciently calm  to  say  to  his  friends  "that  God  was  unjust,  in  that  he  had  made  man 
to  live  without  eating  coca.  I  prefer  a  life  of  ten  years  of  coca  to  one  of  a  thousand 
years  without  it."  As  this  state  was  passing  off,  he  was  seized  with  an  almost  irre- 
sistible desire  to  reproduce  its  delirium  by  taking  more  coca.  Finally,  however,  he 
fell  into  a  condition  of  sleep,  which  lasted  only  three  hours.  After  this  he  was  able 
to  resume  at  once  his  ordinary  occupations,  and  offered  no  physical  evidence  of  his 
coca  debauch. 

The  moderate  daily  use  of  coca,  according  to  our  best  information,  is 
not  injurious,  and  increases  the  working  powers  ;  but,  according  to 
Poeppig,  the  habit  of  excessive  use  is  readily  formed,  and  produces  very 
serious  results.  The  first  symptoms  are  usually  those  of  disorder  of 
the  digestive  organs.  Little  by  little  the  power  of  digestion  is  lost  ;  an 
incurable  insomnia  is  developed,  emaciation  becomes  extreme,  ascites 
appears,  and  the  patient  finally  dies  in  a  condition  of  general  marasmus. 
Other  authors  especially  dwell  upon  the  enfeeblement  of  the  intellectual 
faculties  as  very  marked  in  those  who  use  the  stimulant  to  excess. 
Tschudy  states  that  the  inveterate  coca-chewer  can  be  recognized  by  his 


i98  GENERAL  REMEDIES. 

uncertain  step,  his  general  apathy,  his  sunken  eyes  surrounded  by  a  deep 
purple  aureole,  his  trembling  lips,  his  green  encrusted  teeth,  his  exces- 
sively fetid  breath,  and  the  peculiar  blackness  about  the  corners  of  the 
mouth. 

Pronounced  aphrodisiac  properties  have  been  attributed  to  coca,  but 
they  seem  to  rest  upon  tradition  rather  than  upon  demonstrated  experi- 
ence. According  to  M.  Unanne,  the  ancient  inhabitants  of  Peru  repre- 
sented Venus  by  a  female  figure  with  a  coca-leaf  in  her  hand,  and  the 
coca  still  plays  an  important  part  in  the  nuptial  ceremonies  of  the  Indians. 

It  has  been  affirmed  by  Tschudy  and  Unanne  that  coca  is  able  to  take 
the  place  of  food  ;  but  this  is  clearly  not  the  case.  Weddell  himself 
states  that  although  an  Indian  chewing  the  coca  could  go  on  foot  many 
hours  without  fatigue  and  without  food,  yet  at  the  end  he  would  eat  more 
at  one  repast  than  he  himself  would  take  in  two  days.  He  accords  with 
Bibra8  in  stating  that  coca  has  the  power  of  putting  aside  for  some 
time  the  sense  of  hunger.  While,  however,  it  may  mask  the  appetite,  it 
certainly  does  not  nourish  the  body,  and  it  is  indeed  most  probable  that 
the  absence  of  hunger  is  the  outcome  of  a  local  benumbing  of  the  gastric 
nerves.  Thomas  Moreno  y  Maiz  made  several  crucial  experiments  by 
keeping  animals  in  pairs  without  food,  and  giving  to  one  coca  freely. 
These  experiments  have  been  repeated  by  B.  von  Anrep,9  and  in  every 
case  the  animal  which  received  the  coca  died  at  least  as  early  as  its 
mate. 

The  symptoms  which  have  been  present  in  cocaine-poisoning,  or  have 
been  produced  by  the  coca-leaf  or  its  preparations,  in  the  United  States 
or  in  Europe,  differ  essentially  from  the  descriptions  of  those  said  to  be 
caused  by  the  plant  in  the  South  American  natives.*  We  believe  that  in 
no  recorded  cases  has  there  been  anything  resembling  the  beatific  visions 
and  exhilarations  described  by  Montegazza.  Ordinarily,  in  the  mildest 
cases  of  poisoning  with  us,  there  are  great  restlessness  and  nervous  ex- 
citement, but  no  sense  of  beatitude  ;  rather  a  condition  of  terror.  With 
this  state  come  usually  distinctly  accelerated  pulse,  increased  frequency 
of  respiration,  and,  perchance,  muscular  twitchings  or  even  mild  con- 
vulsions. In  the  more  severe  cases  of  -poisoning  the  symptoms  vary  ; 
sometimes  there  have  been  nausea,  vomiting,  rapid,  almost  imperceptible 
pulse,  great  perspiration,  and  collapse  with  or  without  loss  of  conscious- 
ness ;  in  other  cases  the  pulse  has  been  slow  and  feeble,  and  sometimes 
pronounced  cyanosis,  with  slow  or  almost  arrested  respiration,  has  been 
the  most  alarming  manifestation.  The  pupils  are  usually  dilated,  but 
have  been  reported  in  some  cases  as  ' '  contracted. ' '  After  very  large 
doses  convulsions  usually  occur  ;  they  are  often  violent  and  epileptiform  ; 
not  rarely,  at  times,  at  least,  they  are  partial,  and  in  many  cases  opisthot- 
onos  has  been  pronounced.  Consciousness  rarely  escapes  ;  usually  it  is 


*  The  belief  of  H.  H.  Rusby,  that  these  differences  depend  upon  alterations  of  the 
coca-leaf  during  its  drying  and  transmission  across  the  seas,  has  hardly  been  sustained 
(Therap.  Gaz.,  1888). 


DELIRIFACIENTS.  199 

simply  lost,  but  sometimes  it  is  merged  into  a  mania  with  hallucinations 
and  delusions,  which  mania  may  become  violent  and  even  homicidal,  as 
in  a  case  reported  by  Mattison. 

Very  small  doses  (one-  to  three-one-hundredths  of  a  grain  of  cocaine)  produce 
in  the  frog  no  other  symptoms  than  some  evidences  of  excitement.  After  doses 
of  from  one-tenth  to  one-fiftieth  of  a  grain  the  frog  becomes  quiet,  with  an  apparent 
increase,  however,  in  the  reflex  activity,  sometimes  amounting  to  tetanus,  followed 
by  increasing  palsy  and  failure  of  the  respiration  ;  very  large  doses  produce  symp- 
toms of  paralysis. 

In  the  domestic  animals  the  symptoms  vary.  In  the  rabbit  there  is  first  a  pecu- 
liar state  of  quiet,  followed  in  a  few  moments  by  a  condition  of  great  excitement, 
in  which  the  animal  springs  and  jumps  about.  A  few  minutes  later  the  rabbit  again 
becomes  quiet,  and  now,  although  trembling  much,  is  so  weak  that  he  moves  with 
difficulty.  The  tremblings  increase  until  they  merge  in  convulsive  movements  of 
the  legs,  while  at  the  same  time  there  is  partial  paraplegia  ;  pendulum  movements 
of  the  head  are  very  marked,  and  finally  epileptiform  convulsions  appear,  while 
simultaneously  a  peculiar  tetanic  rigidity  seems  to  indicate  spinal  excitement.  The 
lethal  dose  for  a  rabbit  is  put  at  a  grain  and  a  half  per  kilo.  Dogs  and  cats  are 
said  to  be  more  susceptible  to  the  action  of  cocaine  than  is  the  rabbit,  and  to  suffer 
similar  symptoms,  but  especially  with  the  dog  the  evidences  of  mental  excitement 
are  more  pronounced. 

According  to  Von  Anrep,  after  an  injection  of  cocaine  the  dog  will  dance 
and  leap,  never  standing  still  for  a  moment,  and  continually  circling  around  the 
experimenter.  The  movements  are  not  at  all  those  of  convulsions,  but  voluntary, 
and  accompanied  by  every  expression  of  joy  and  exhilaration.  This  may  continue 
for  hours,  the  animal  then  becoming  gradually  quiet,  and  passing  finally  into  his 
normal  condition.  If  instead  of  a  moderate  dose  a  toxic  one  has  been  given,  there 
is  first  a  period  in  which  the  animal  is  very  restless  but  seems  full  of  terror  and 
anxiety  ;  the  least  sound  frightens  him,  causing  him  to  tremble  and  to  drop  his  tail 
between  his  legs.  He  does  not  appear  at  this  time  to  know  his  master.  Rhyth- 
mical movements  of  almost  all  portions  of  the  body  accompany  this  state.  Fifteen 
or  twenty  minutes  later  the  mental  condition  alters,  and  the  dog  becomes  appar- 
ently full  of  joyous  excitement.  He  barks  loudly,  runs  from  one  person  to  another, 
licking  them,  and  giving  all  the  characteristic  signs  of  joy.  After  a  few  moments 
this  condition  gives  way  to  one  of  increasing  feebleness  ;  the  dog  gradually  be- 
comes unable  to  move,  rhythmical  movements,  cramps,  and  convulsive  symptoms 
appear ;  the  pendulum-like  swinging  of  the  head  gets  very  violent,  and  at  last 
narcosis,  with  epileptiform  convulsions,  develops.  It  is  evident  that  many  of  these 
symptoms  are  psychical. 

Nervous  System. — L.  Dadd*1  states  that  distinct  histological  changes 
can  be  recognized  in  the  cells  of  the  nerve-centres  as  the  result  of  poison- 
ing with  cocaine,  and  that  these  lesions  are  most  marked  in  the  cerebral 
cortex. 

B.  von  Anrep  believes  that  the  drug  has  a  very  distinct  and  peculiar 
influence  upon  the  semicircular  canals,  thereby  causing  the  peculiar  pen- 
dulum-like motions  of  the  head,  the  lack  of  coordination,  and  the  rolling 
convulsions  especially  seen  in  doves. 

Spinal  Cord. — According  to  the  researches  of  Von  Anrep,  the  con- 
vulsive movements  are  of  cerebral  origin,  and  are  arrested  by  section  of 
the  spinal  cord  ;  but  the  experiments  of  L.  I.  Tumass 10  indicate  that 
they  do  not  arise  in  the  psycho-motor  centres  of  the  brain-cortex,  since 


200  GENERAL  REMEDIES. 

he  found  not  only  that  the  local  application  of  cocaine  lessens  the  irrita- 
bility of  these  centres,  but  also  that  during  the  convulsive  stage  of  cocaine- 
poisoning  the  centres  are  less  sensitive  than  normal.  Danini,  more- 
over, appears  to  have  found  that  section  of  the  cord  does  not  prevent  con- 
vulsions in  the  hind  feet,  and  the  experiments  of  Mosso  show  that  when 
the  upper  cord  is  cut  in  the  dog  and  the  animal  cocainized,  the  irritation 
of  the  nerve-trunk  or  of  the  surface  will  produce  in  a  little  while  general 
muscular  rigidity.  Both  Mosso  and  Von  Anrep  are  in  accord  with  other 
observers  in  stating  that  reflex  activity  is  at  first  increased  by  cocaine, 
and  the  evidence  seems  to  show  that  while  the  convulsive  movements  of 
the  poisoned  animal  originate  chiefly  in  the  brain,  yet  there  is  a  primary 
stage  of  excited  reflex  activity,  the  result  of  a  direct  action  upon  the 
spinal  cord.  The  motor  paralysis  and  the  loss  of  reflex  activity  which 
finally  occur  in  cocaine-poisoning  are  probably  in  part  the  result  of  an 
influence  upon  the  nerves  ;  but  that  they  are  chiefly  due  to  a  direct  seda- 
tive action  upon  the  spinal  cord  seems  to  follow  from  the  experiments  of 
Mosso,  who  found  that  when  he  so  bound  the  hind  legs  of  the  frog  as  to 
prevent  the  access  of  cocaine  to  the  nerves,  there  was  a  rapid  loss  of  reflex 
activity,  and  indeed  a  complete  paralysis,  at  a  time  when  both  the  motor 
and  the  sensory  nerves  were  still  intact. 

An  observation  made  at  a  certain  stage  of  the  poisoning  by  Dr.  Ott 
— viz. ,  that  irritation  of  the  posterior  column  of  the  spinal  cord  produced 
no  effect,  while  a  prick  of  the  anterior  column  was  followed  by  the  usual 
result — indicates  that  there  is  the  same  difference  in  action  upon  the 
sensory  and  motor  tracts  as  upon  the  corresponding  nerve-trunks  ;  but 
Mosso' s  experiments  upon  tritons  led  him  to  conclude  that  the  power  of 
conducting  impulses  efferently,  or  from  the  centre,  is  first  lost  in  the 
spinal  cord  poisoned  with  cocaine. 

Nerves. — Almost  all  observers  agree  that  the  sensory  nerves  after  suf- 
ficient doses  are  finally  paralyzed  in  cocaine-poisoning  ;  but  Mosso " 
believes  that  the  respiratory  centre  is  more  susceptible  to  the  action  of 
cocaine  than  are  the  sensory  nerves,  and  certainly  doses  of  the  alkaloid 
not  dangerous  to  life  have  no  perceptible  general  effect  upon  the  sensory 
nerves.  The  experiments  of  Nikolsky,  of  B.  von  Anrep,  of  Ott,  and  of 
Laffont  seem  to  prove  that  the  sensory  paralysis  is  preceded  by  increased 
functional  activity,  which  is  in  accord  with  the  observation  of  Mosso,  that 
in  doses  of  0.05  to  o.  i  gramme  cocaine  increases  in  man  the  sensibility 
of  the  skin. 

According  to  Danini,  the  motor  nerves  in  the  frog  remain  irritable 
until  after  death  ;  but,  according  to  Nikolsky,  their  functional  activity 
is  first  increased  and  afterwards  destroyed.  Ott  also  asserts  that  co- 
caine depresses  the  motor  nerves.  Moreno  y  Maiz  found  that  when 
he  tied  the  iliac  artery  of  a  frog  on  one  side  and  administered  cocaine 
anteriorly,  there  came  a  time  when  irritation  of  the  poisoned  limb 
caused  no  movement,  while  irritation  of  the  protected  extremity  pro- 
voked very  distinct  general  reflexes  ;  at  the  same  time  there  was  dimin- 


DELIRIFACIENTS.  201 

ished  motility  in  the  non-protected  limb  as  compared  with  the  pro- 
tected one  :  facts  which,  of  course,  indicate  that  the  drug  finally  depresses 
both  motor  and  sensory  fibres,  but  that  its  action  upon  the  motor  is 
subordinate  to  that  upon  the  sensory  nerves.  Ott  also  noticed  that 
there  is  a  time  in  the  poisoning  when  irritation  of  the  central  end  of  a 
cut  sciatic  nerve  produces  no  response,  while  irritation  of  its  peripheral 
end  causes  muscular  action,  and  thereby  confirms  the  view  that  the  drug 
affects  the  sensory  earlier  and  more  powerfully  than  the  motor  nerves. 
H.  Alms  found 12  that  a  five  per  cent,  solution  of  cocaine  in  contact  with 
the  isolated  ischiatic  plexus  of  the  frog  caused  absolute  anaesthesia  of  the 
leg  and  apparent  loss  of  motor  power,  the  leg  lying  motionless  and  trail- 
ing behind.  Nevertheless,  strong  irritation  upon  the  front  leg  of  the  frog 
caused  immediate  movements  which  were  shared  by  the  cocainized  hind 
leg,  showing  that  the  motor  filaments  were  not  paralyzed.  The  experi- 
ments of  Alms  indicate  that  the  extreme  peripheral  filaments  of  the  nerve 
are  first  affected,  since  at  a  certain  period  most  severe  irritation  of  the 
skin  produced  no  pain  in  the  poisoned  rabbit,  although  the  injection  of 
irritating  materials  evidently  caused  violent  pain. 

The  discovery  of  Mosso,  that  the  local  application  of  cocaine  sus- 
pends functional  activity  in  motor  nerves,  has  been  confirmed  by  L. 
Popielski,13  and  it  must  be  considered  as  demonstrated  that  cocaine  is  a 
paralyzant  to  both  motor  and  sensory  nerves,  although  it  acts  much  more 
powerfully  upon  the  sensory  nerves. 

According  to  Verebe'ly  and  Horvdth40,  the  action  of  cocaine  upon  the 
nerve-endings  is  so  pronounced  that  demonstrable  changes  can  be  noted 
after  it  has  been  applied  locally. 

Circulation. — The  action  of  cocaine  upon  the  circulation  is  in  some 
details  so  complex  that  in  spite  of  much  work  it  is  not  yet  fully  understood, 
but  in  the  main  our  knowledge  concerning  it  is  clear.  The  concordant 
experimental  results  obtained  by  Ott,  by  Von  Anrep,  by  Vulpian,  by 
Laborde,  by  Nikolsky,  by  Danini,  and  by  Reichert1*  show  that  the 
moderate  dose  of  cocaine  produces  an  increase  in  the  arterial  pressure. 

It  is  true  that  some  of  these  experimenters  employed  only  non-curarized  ani- 
mals, but  others  practised  curarization  and  artificial  respiration,  so  that  it  must 
be  acknowledged  that  whilst  disturbance  of  the  respiratory  and  muscular  system, 
by  the  alkaloid  may  secondarily  increase  the  blood-pressure,  yet  it  has  the  power 
of  directly  increasing  the  arterial  pressure.  The  fact  that  various  experimenters 
have  failed  to  obtain  the  increase  of  pressure  just  spoken  of  is  in  some  cases  to  be  ex- 
plained by  their  having  used  too  large  doses,  all  investigators  agreeing  that  the  too 
large  dose  of  cocaine  finally  decreases  pressure  ;  in  other  cases,  when  small  doses 
of  cocaine  were  employed  (Berthold 15),  it  is  probable  that  so  much  curare  had  been 
given  that  the  drugged  heart  and  blood-vessels  were  unable  to  respond  to  a  new 
poison  :  certainly  the  evidence  is  overwhelming  that  cocaine  directly  increases 
blood-pressure. 

The  experiments  of  Danini,  of  Berthold,  and  of  Reichert  are  con- 
cordant in  showing  that  after  section  of  the  spinal  cord  alone,  or  of  the 
spinal  cord  and  the  vagi,  cocaine  does  not  distinctly  increase  the  arte 


202  GENERAL  REMEDIES. 

rial  pressure, — proof  that  the  chief  cause  of  the  rise  of  the  arterial  press- 
ure under  the  influence  of  cocaine  is  centric  vaso-motor  spasm. 

Concerning  the  action  of  cocaine  upon  the  heart  itself  there  is  such 
conflict  of  testimony  as  to  require  further  experimentation  before  positive 
conclusions  can  be  reached,  but  the  drift  of  the  present  evidence  is  to 
show  that  the  small  dose  of  cocaine  moderately  stimulates  the  heart,  and 
that  the  large  toxic  dose  finally  depresses  it. 

As  showing  the  stimulant  action  of  the  small  dose  of  cocaine,  Mosso  and  H.  G. 
Beyer,16  as  the  result  of  their  experimental  studies,  made  in  the  one  case  on  the  cut- 
out frog's  heart,  in  the  other  upon  the  isolated  heart  of  the  terrapin,  found  that  the 
minute  dose  of  the  alkaloid  increased  the  whole  amount  of  force  put  out  by  the 
heart,  as  well  as  the  power  of  the  individual  systolic  contraction  ;  whilst  Pachon 
and  Moulinier,17  in  experiments  with  cocaine  on  the  heart  of  the  frog  in  situ,  find 
that  after  a  moderate  dose  of  cocaine  there  is  a  hypertonicity  of  the  heart  due  to  a 
direct  action  upon  the  muscular  fibres.  Observers  affirm  that  the  heart  of  the  mam- 
mal is  arrested  by  the  toxic  dose  in  diastole,  which  is  in  accord  with  the  statements 
of  Yon  Anrep  and  Nikolsky  concerning  the  heart  of  the  frog  and  of  H.  G.  Beyer 
concerning  that  of  the  terrapin,  diastolic  arrest  being  affirmed  by  all  these  investi- 
gators. Pachon  and  Moulinier  declare  that  the  ventricles  are  arrested  in  systole, 
the  auricles  in  diastole.  According  to  these  investigators,  the  arythmia  of  advanced 
cocaine-poisoning  is  really  a  rhythm  which  differs  from  the  normal  in  that  the  con- 
tractions occur  in  regular  groups  ;  later  there  is  a  dissociation  of  the  auricular  and 
ventricular  rhythms. 

The  fact  that  section  of  the  spinal  cord — that  is,  separation  of  the 
general  capillaries  of  the  body  from  the  vaso-motor  centres — largely  or 
altogether  prevents  the  rise  of  arterial  pressure  produced  by  cocaine  indi- 
cates that  the  alkaloid  has  little  or  no  direct  influence  upon  the  vessels 
themselves,  but  the  matter  is  not  as  clear  as  appears  at  first  sight. 

The  evidence  as  to  the  facts  is  contradictory.  Mosso  found  that  when  he  ex- 
perimented with  artificial  circulation  upon  extirpated  kidneys  small  doses  of  cocaine 
had  no  sensible  effect  upon  the  blood-vessels  ;  and  Durdufi  states  that  marked  nar- 
rowing of  the  vessels  of  the  rabbit's  ear  can  be  seen  when  cocaine  is  injected,  but 
is  prevented  by  previous  section  of  the  sympathetic.  Contrariwise,  H.  G.  Beyer 
found  in  experiments  upon  the  terrapin  that  both  large  and  small  doses  of  cocaine 
produce  contraction  of  the  blood-vessels  by  a  direct  influence  ;  and  Laffont  experi- 
mentally reached  the  conclusion  that  one  of  the  chief  actions  of  cocaine  is  to  con- 
tract the  blood-vessels  by  affecting  the  nerve-endings  in  their  walls.  The  results  of 
the  plethysmographic  studies  of  Mosso — namely,  that  in  man  therapeutic  doses  of 
cocaine  cause  contraction  of  the  blood-vessels — have  no  bearing  upon  the  matter  in 
hand,  since  such  contraction  might  or  might  not  be  of  centric  origin.  It  should 
also  be  stated  that  in  some  of  Reichert's  experiments  there  was  a  slight  rise  in  the 
arterial  pressure  produced  by  cocaine  after  section  of  the  cord. 

The  well-known  constringing  of  blood-vessels  by  the  local  application 
of  cocaine  can  hardly  be  explained  except  by  attributing  to  the  alkaloid 
the  power  of  acting  upon  the  blood-vessel  walls.  It  should  be  noted 
that  in  such  cases  the  cocaine  is  brought  in  enormous  quantities  and 
great  concentration  into  contact  with  the  blood-vessels  ;  and  in  view  of 
the  contradiction  in  the  experimental  evidence,  the  most  probable  con- 
clusion is  that  cocaine  has  direct  relations  with  the  muscle-fibres  in  the 


DELIRIFACIENTS.  203 

arteriole  walls,  but  that  it  acts  so  feebly  upon  them  in  comparison  with 
its  influence  upon  nerve-centres  that  even  in  general  poisoning  with  the 
alkaloid  the  influence  upon  the  blood-vessel  walls  is  overshadowed  by  the 
much  greater  powers  of  the  drug. 

The  results  of  the  studies  made  by  various  investigators  with  the 
direct  application  of  cocaine  to  the  heart  lead  to  the  conclusion  that 
whilst  small  doses  of  the  alkaloid  feebly  stimulate  the  viscus,  toxic  doses 
act  as  a  depressant  and  finally  as  a  paralyzant  ;  that  cardiac  depression  is 
one  of  the  causes  of  low  arterial  pressure  in  advanced  cocaine-poisoning 
is  further  evidenced  by  the  rapid  and  immediate  fall  in  the  pressure  which 
occurs  when  cocaine  is  injected  into  a  dog  whose  spinal  cord  has  been  cut 
and  vaso- motor  system  paralyzed.*  The  opinion  of  Reichert,  that  widen- 
ing of  the  blood-paths  by  vaso- motor  paralysis  is  the  most  important 
factor  in  the  causation  of  lowered  blood-pressure  in  advanced  cocaine- 
poisoning,  seems  to  be  so  far  correct  that  the  probabilities  are  that  such 
widening  of  the  blood-paths  occurs. 

The  testimony  as  to  the  action  of  the  alkaloid  upon  the  pulse-rate  and 
upon  the  inhibitory  nerves  of  the  heart  is  so  various  that  no  positive  con- 
clusions are  warranted  without  further  study. 

Von  Anrep  states  that  the  pulse-rate  is  usually  increased,  but  that  this  increase 
is  not  marked  in  rabbits,  while  in  Ott's  experiments  upon  dogs  the  pulse  usually 
becomes  slower.  Von  Anrep  also  states  that  the  vagi  are  paralyzed  by  large  doses 
of  cocaine,  while  Ott,  Nikolsky,  Laffont,  and  Durdufi  18  declare  that  it  does  not 
affect  the  vagi,  and  Berthold  states  that  previous  section  of  the  vagi  has  no  effect 
upon  the  course  of  the  symptoms  caused  by  cocaine. 

Reichert  found  in  an  elaborate  series  of  studies  that  by  small  doses  of  cocaine 
the  pulse-rate  is  at  first  decreased,  then  increased,  and  finally  decreased.  In  regard 
to  the  causes  of  the  alterations  of  the  pulse  he  came  to  the  following  conclusions  : 

"Very  small  doses  of  cocaine  decrease  the  rate  by  stimulating  the  cardio-inhibi- 
tory  centres  ;  small  to  moderate  doses  increase  the  rate  by  depressing  these  cen- 
tres, and  in  some  cases  by  depressing  also  the  cardio-inhibitory  ganglion  ;  large 
doses  cause  a  transient  decrease,  followed  by  a  rise  or  a  permanent  decrease,  the  de- 
crease being  due  to  a  depression  of  the  accelerator  or  motor  ganglion  in  the  heart, 
and  the  increase  to  the  factors  before  mentioned.  The  cardio-inhibitory  centres  are 
invariably  affected,  being  primarily  stimulated  and  secondarily  depressed." 

Muscles. — Although  there  is  some  contradiction  of  evidence,  yet  our 
knowledge  of  the  effect  of  cocaine  upon  the  striated  muscles  is  sufficient 
for  positive  conclusions. 

Alms,  Nikolsky,  and  B.  von  Anrep  state  that  the  striated  muscles  are  not  affected 
by  the  alkaloid,  while  Ott  affirms  that  it  acts  upon  them  like  veratrine,  and  is  con- 
firmed in  this  by  Buchheim  and  Eisenmenger.19  The  tracings  given  by  Ott  would 
appear  to  prove  that  the  muscular  contraction  is  prolonged  by  cocaine,  and  can 
hardly  be  accounted  for  by  a  condition  which  M.  J.  Rossbach  and  B.  von  Anrep 
allege  to  be  produced, — viz.,  a  peculiar  sensibility  of  the  muscle  similar  to  that  pro- 
duced by  curare,  and,  like  it,  caused  by  a  lessening  of  muscle-tonus  by  paralysis  of 
the  peripheral  nerve-endings. 

*  See  experiments  of  I.  Ott,  Toxicological  Studies,  1874,  30. 


204  GENERAL  REMEDIES. 

The  results  obtained  by  Otffind  such  confirmation  in  the  experiments 
of  Berthold  upon  the  effects  of  the  local  application  of  cocaine  upon  the 
frog's  muscle,  and  in  those  of  Mosso,  who  found  that  in  the  frog,  the 
dog,  and  the  man  the  excitability  of  the  muscles  is  increased  by  small 
doses,  and  paralyzed  by  large  doses  of  cocaine,  that  it  must  be  considered 
established  that  cocaine  is  a  muscle  poison,  stimulating  and  afterwards 
depressing  the  functional  activity.  This  influence  of  the  alkaloid  is, 
however,  probably  too  slight,  as  compared  with  its  effects  upon  other 
portions  of  the  organism,  to  be  very  apparent  in  general  poisoning. 
Nevertheless,  in  the  ergographic  experiments  of  Benedicenti 20  cocaine 
both  heightened  muscular  energy  and  increased  resistance  to  fatigue,* 
whilst  Mosso  found  that  in  man,  when  the  muscles  were  exhausted  by 
work  and  fasting,  the  exhibition  of  cocaine  in  the  dose  of  a  grain  and  a 
half  more  than  doubled  the  response  to  stimuli.  These  experiments 
throw  a  peculiar  light  upon  the  assertions  of  travellers,  that  cocaine  in 
the  South  American  Indians  enormously  increases  the  power  of  with- 
standing fatigue.  The  present  difficulty  in  the  way  of  the  full  acceptance 
of  the  natural  deductions  from  them  is  the  fact  that  in  America  and  in 
Europe  cocaine  has  appeared  to  fail  as  a  stimulant  during  fatiguing 
labors. 

Temperature. — The  rise  of  rectal  temperature  in  cocaine-poisoning 
sometimes  amounts  to  as  much  as  8°  F.  It  is  certainly  not  due  to  the 
convulsions,  as  it  usually  occurs  before  the  motor  disturbance,  t  In  fatal 
cases  it  is  followed  by  a  fall,  so  that  before  death  the  temperature  may 
become  subnormal.  In  the  calorimetrical  experiments  of  Reichert,  the 
rise  of  temperature  was  found  to  be  due  to  a  great  increase  in  the  heat 
production. 

Reichert "  has  further  determined  that  after  section  of  the  spinal  cord \ 
at  its  junction  with  the  medulla,  as  well  as  after  section  of  the  crura  cerebri, 
cocaine  is  powerless  to  produce  rise  of  the  temperature,  and  therefore 
concludes  that  the  rise  of  temperature  produced  by  cocaine  is  of  cerebral 
origin,  and  is  due  to  stimulation  of  the  thermogenic  centres  in  the  cau- 
date nucleus  and  to  motor  excitement  produced  by  stimulation  of  the 
cortical  motor  centres. 

Urinary  Secretion — Such  varying  results  have  been  recorded  by 
clinicians  as  to  the  effect  of  cocaine  upon  the  amount  of  urinary  secretion 
that  its  action  is  probably  not  constant.  According  to  Bignon,21  the 
single  large  dose  may  produce  an  anuria  so  prolonged  as  to  bring  on 
uraemic  symptoms.  There  is  some  reason  for  believing  that  cocaine  re- 

*  Sobieranski  believes,  however,  that  the  effect  of  cocaine  is  through  the  nerve-cen- 
tres (see  Gazetta  Lekarska,  1896,  No.  4). 

t  P.  Langlois  and  Charles  Richet  have  found  that  the  temperature  of  the  cocainized 
animal  has  a  great  effect  in  determining  the  amount  of  cocaine  necessary  to  produce 
convulsions.  The  higher  the  temperature  the  smaller  the  dose  necessary,  and  when  the 
animal  was  kept  at  a  temperature  of  39°  C.,  only  tonic  convulsions  were  produced. 

t  The  rise  of  temperature  which  has  been  noted  by  Mosso  after  section  of  the  spinal 
cord  may  have  been  the  result  of  imperfect  division. 


DELIRIFACIENTS.  205 

duces  the  nitrogenous  elimination,  but  the  experiments  upon  the  subject 
are  hardly  sufficient  to  warrant  the  positive  conclusion  that  the  alkaloid 
checks  protoplasmic  waste. 

I.  Ott  and  Atherton  P.  Mason  w  have  found  that  when  cocaine  is  taken  habit- 
ually it  not  only  lessens  the  urinary  secretion  but  also  markedly  decreases  the 
elimination  of  urea,  whilst  in  three  experiments  Richard  Fleischer  determined  that 
the  alkaloid  markedly  reduces  nitrogenous  elimination.  Mason  experimented  with 
very  large  therapeutic  doses  of  cocaine  taken  during  prolonged  exercise,  and  states 
that  his  results  were  contrary  to  those  previously  reached  by  Gazeau. 

In  Ott's  experiments  the  urine,  under  the  influence  of  cocaine,  became 
full  of  calcium  oxalates.  Sugar  and  albumin  have  been  frequently  noted 
in  the  urine  of  poisoned  animals,  but  Von  Anrep  affirms  that  their  pres- 
ence is  due  to  the  prolonged  asphyxia  induced  by  the  drug. 

Eye. — When  a  watery  solution  of  cocaine  is  dropped  into  the  eye 
there  occurs  a  slight  contraction  of  the  pupil,  followed  within  a  few 
minutes  by  dilatation.  The  first  contraction  is  probably  reflex  and  due 
to  the  irritation  of  the  conjunctiva.  The  maximum  dilatation  for  a  four 
per  cent,  solution  is  usually  reached  about  the  end  of  the  first  hour  ;  an 
hour  later  it  has  sensibly  begun  to  decline,  and  in  from  twelve  to  twenty- 
four  hours  the  pupil  returns  to  normal.  The  dilated  pupil  is  to  some 
extent  responsive  to  light  and  to  accommodation,  the  mydriasis  can  be 
rapidly  overcome  by  eserine,  and,  according  to  Limbourg,2*  increased  by 
atropinization.  The  dilatation  of  the  pupil  is  certainly  due  to  a  peripheral 
influence  which  appears  to  be  a  double  one,  namely, — stimulation  of  the 
sympathetic  nerve  endings  and  paralysis  of  the  oculo-motor  endings. 

The  experiments  of  Nikolsky,  Holtzke,  Limbourg,  as  well  as  of  Scholer  and 
Pfliiger  (quoted  by  Limbourg),  show  that  cocaine  applied  to  the  eye  immediately 
after  section  of  the  sympathetic  does  dilate  the  pupil,  although  later,  when  suffi- 
cient time  has  elapsed  for  degeneration  of  the  sympathetic  fibres  to  occur,  the  alka- 
loid is  powerless.  This  would  appear  to  prove  that  cocaine  dilates  the  pupil  by 
stimulating  the  sympathetic  nerve-endings  ;  but,  according  to  Schultz,  very  strong 
solutions  of  cocaine  will  dilate  the  pupil  after  nerve  degeneration  has  occurred, 
though  weaker  solutions  fail  to  act.  Further,  Schultz  found  that  when,  in  the  cat, 
he  extirpated  the  superior  cervical  ganglion  on  one  side,  waited  a  sufficient  length 
of  time  for  degeneration  of  the  dilator  nerves,  and  then  applied  cocaine  to  both 
eyes,  he  obtained  a  maximal  dilatation  on  the  unoperated  side,  but  a  medium  dilata- 
tion on  the  operated  side.  Allowing  the  correctness  of  Schultz's  experiments, 
the  double  action  of  cocaine  appears  to  be  demonstrated.  Limbourg  states  that 
electrical  irritation  of  the  cornea  may  restore  to  such  an  eye  the  power  of  respond- 
ing to  cocaine. 

Respiration. — Small  doses  of  cocaine  increase  distinctly  the  rapidity 
of  the  respiration,  and  in  some  cases  also  the  depth  (Von  Anrep,  Mosso, 
Danini,  Ott,  and  Nikolsky).  After  toxic  doses  the  respirations  become 
at  first  rapid  and  more  shallow,  then  irregular  with  interruptions,  after 
each  of  which  the  respiratory  movements  begin  deep  and  slow,  but  be- 
come more  rapid  and  shallow  until  the  next  stand-still.  As  Mosso  found 


206  GENERAL  REMEDIES. 

that  after  section  of  the  vagi  cocaine  causes  an  enormous  increase  of  the 
rapidity  of  the  breathing  and  at  the  same  time  so  modifies  the  rhythm 
that  expiration  is  no  longer  quicker  than  inspiration,  it  must  be  con- 
sidered that  the  drug  acts  directly  upon  the  respiratory  nerve-centres  as 
a  respiratory  stimulant.  The  first  stimulant  effect  of  cocaine  upon  the 
respiratory  centres  appears  to  be  followed  after  fatal  doses  by  a  paralyzing 
influence  which  leads  to  death  from  asphyxia. 

Intestines. — According  to  Von  Anrep,  the  intestinal  peristalsis  is 
markedly  increased  by  moderate  doses.  After  large  doses  this  increase 
is  followed  by  great  sluggishness  deepening  into  paralysis.  Tarchanoff 
states  that  coca  increases  the  mucous  secretions,  but  Von  Anrep  affirms 
that  it  decreases  them.* 

SUMMARY. — Cocaine  is  a  cerebral  stimulant,  producing  peculiar 
mental  excitement,  ending  after  large  toxic  doses  in  narcosis,  with  epi- 
leptiform  convulsions,  •which  are  probably  of  cerebral  origin.  In  the 
poisoning  there  is  at  first  increased  reflex  activity,  followed  by  paralysis 
of  voluntary  motion  and  of  reflex  activity,  which  are  chiefly  due  to  a 
direct  action  upon  the  spinal  cord,  the  sensory  side  of  the  cord  being 
probably  more  sensitive  to  the  drug  than  the  motor  side.  Toxic  doses 
depress  and  finally  paralyze  the  sensory  nerves,  and  in  a  much  less 
degree  the  motor  nerves.  Our  present  physiological  knowledge  estab- 
lishes the  fact  that  cocaine  in  moderate  dose  is  a  mild  stimulant,  in  over- 
dose a  depressant,  to  the  circulation,  the  primary  rise  being  chiefly  due 
to  narrowing  of  the  blood-paths  by  stimulation  of  the  vaso-motor  cen- 
tres. Upon  the  heart  itself  the  moderate  dose  of  the  alkaloid  acts  pri- 
marily as  a  stimulant,  increasing  to  a  slight  extent  the  amount  of  force 
put  forth  by  the  heart.  There  is  also  reason  for  believing  that  co- 
caine exerts  a  direct  influence  upon  the  coats  of  the  blood-vessels, 
which  is,  however,  so  feeble  as  not  to  be  of  practical  importance  except 
when  the  cocaine  is  applied  locally.  The  fall  of  blood-pressure  pro- 
duced by  the  toxic  dose  of  cocaine  appears  to  be  due  to  a  direct  depres- 
sion of  the  heart  itself,  aided  by  a  widening  out  of  the  blood-paths, 
probably  through  paralysis  of  the  vaso-motor  centres.  Upon  striated 
muscles  cocaine  appears  to  have  a  peculiar  though  very  feeble  action, 
•which  is  not  manifested  during  poisoning  by  it.  It  has  been  asserted 
that  cocaine  acts  as  a  powerful  diuretic,  but  the  drift  of  present  evidence 
is  to  show  that  it  has  no  definite  influence  upon  the  amount  of  urine 
secreted:  the  evidence  available  indicates  that  it  decreases  elimina- 
tion of  urea.  Upon  the  eye  cocaine  acts  as  an  energetic  mydriatic. 
It  is  a  powerful  stimulant  to  the  respiratory  centres,  increasing  the 
rapidity  and  fulness  of  the  respirations,  but  if  the  dose  be  sufficiently 
large  it  after  a  time  causes  the  respirations  to  become  very  shallow, 
and  finally  paralyzes  the  respiratory  centres.  Moderate  doses  are  said 
to  increase,  large  doses  to  paralyze,  peristalsis. 

THERAPEUTICS. — By  its  constringing  influence  upon  the  blood-vessels, 
as  well  as  by  its  local  effect  upon  the  sensory  nerves,  cocaine  is  a  valuable 
local  remedy.  In  acute  coryza  a  ten  per  cent,  solution  applied  to  the 
nostrils  will  sometimes  afford  permanent  relief,  but  a  combination  of  a  four 

*  M.  E.  Gley  states  (Compt.-Rend.  Soc.  Biol.,  iii.  560)  that  when  cocaine  is  injected 
into  the  portal  vein  it  produces  comparatively  little  effect,  and  he  believes  that  it  is 
destroyed  in  the  liver.  This  is  criticised  by  Chouppe  (Ibid.). 


DELIRIFACIENTS.  207 

per  cent,  solution  with  bismuth  (three  drachms  to  the  ounce  of  mucilage) 
is  more  generally  useful.  It  should  be  applied  by  means  of  a  dropper 
every  three  or  four  hours.  In  hay  fever,  in  the  peculiar  irritated  sore 
throat  of  advanced/^/^ww,  in  chronic  laryngitis,  in  inflamed  hemorrhoids , 
in  fissure  of  the  anus,  and  even  in  open  cancer  its  application  will 
often  afford  temporary  relief.  In  some  cases  of  dysentery  with  excessive 
nervous  irritability  of  the  rectum,  cocaine  suppositories  are  of  great  ser- 
vice. Cocaine  is  also  sometimes  useful  as  a  local  haemostatic  in  arresting 
nasal  and  other  mucous  membrane  hemorrhages. 

For  local  use  the  two  to  ten  per  cent,  solution  may  be  employed,  care 
being  exercised  not  to  use  a  possibly  fatal  dose  of  the  drug. 

Internal  Use. — As  an  internal  medicament  cocaine  is  useful  as  a  re- 
spiratory stimulant  and  as  a  tonic,  especially  to  the  circulation.  It  is 
largely  used  in  the  same  class  of  cases  in  which  strychnine  is  found  to  be 
available.  Less  powerful  in  its  influence  than  is  strychnine,  it  is  espe- 
cially useful  as  an  aid  to  that  alkaloid.  (See  Respiratory  Stimulants.) 
Its  stimulant  influence  upon  the  cerebrum  naturally  led  to  the  expectation 
that  it  would  be  of  value  in  cases  of  depression  of  spirits  and  even  of  true 
melancholia.  The  results  of  our  own  experience,  after  thorough  trial, 
however,  are  in  accord  with  the  generally  expressed  opinions  of  alienists, 
that  it  has  no  remedial  value  in  any  form  of  mental  aberration.  Some- 
times it  appears  to  produce  at  first  a  temporary  relief,  but  this  does  not 
continue  ;  and  if  the  remedy  be  pushed,  anorexia,  restlessness,  or  other 
disagreeable  symptoms  usually  demand  its  withdrawal.  In  neurasthenia 
and  hysteria  it  is  valuable  only  as  a  stimulant  and  stomachic,  acting 
better  in  the  form  of  the  fluid  extract  than  cocaine  itself ;  and  in  all  these 
cases  there  is  especially  the  danger  of  the  formation  of  the  cocaine  habit. 
Large  doses  of  the  fluid  extract  are  sometimes  of  service. 

In  the  form  of  large  doses  of  the  fluid  extract,  coca  has  appeared  to  us 
to  be  of  service  during  the  breaking  off  of  the  opittm  habit,  exerting  some 
stimulant  influence  upon  the  nervous  system,  and  restraining  the  tendency 
to  diarrhoea  and  loss  of  appetite.  Some  European  clinicians  have  found 
cocaine  of  service  in  the  treatment  of  serous  diarrhceas.  It  is  undoubt- 
edly of  value  for  the  relief  of  excessive  vomiting,  especially  when  due  to 
gastric  irritation.  Thomas  D.  Dunn  2*  states  that  hypodermic  injections 
of  one  grain  control  the  pain  of  migraine.  Aschenbraidt 2D  asserted  that, 
in  doses  of  0.15  grain,  cocaine  was  a  valuable  stimulant  during  forced 
marches  ;  but  in  a  series  of  careful  trials  with  it  by  the  medical  rowing 
crew  of  the  University,  it  appeared  to  have  no  value,  and  the  general 
experience  seems  to  conform  with  this  result. 

ADMINISTRATION. — The  official  salt  of  cocaine  (COCAINE  HYDRO- 
CHLORIDUM,  U.  S. )  may  be  given  in  doses  of  one-sixth  to  one-half  a  grain 
(0.01-0.03  Gm. )  ;  the  cruder  preparations  of  the  drug  are  at  present 
rarely  used.  The  dose  of  the  official  fluid  extract  (FLUIDEXTRACTUM 
,  U.  S. )  is  one-half  to  two  fluidrachms  (1.9—7.5  C.c. ). 

TOXICOLOGY. — The  number  of  cases  of  poisoning  by  cocaine  is  very 


208  GENERAL  REMEDIES. 

great,  and  although  large  doses  have  been  recovered  from,  excessively 
violent  symptoms  have  followed  the  use  of  smaller  amounts.  It  is  re- 
markable, also,  that  in  many  of  these  cases  the  drug  has  been  employed 
for  a  local  effect. 

The  fatal  cases,  to  the  details  of  which  we  have  had  access,  are  those  reported 
by  Kolomnin,  twenty-four  grains  into  the  rectum  for  local  anaesthesia ;  F.  M. 
Thomas,  four  per  cent,  solution  used  locally  for  toothache,  in  unknown  quantity  ; 
Knabe,  four  per  cent,  solution,  twelve  drops  given  hypodermically  to  a  girl  of 
eleven  years,  death  in  forty  seconds  (for  details,  see  J.  B.  Mattison26)  ;  J.  H.  C. 
Simes,"  one  drachm  of  twenty  per  cent,  solution  injected  into  the  urethra,  fol- 
lowed immediately  by  violent  convulsions,  ending  in  death  in  twenty  minutes, 
autopsy  proved  that  urethra  was  not  ruptured.  A  fatal  case  is  said  to  have  been 
reported  in  Odontologie,  1890,  x.  Half  an  ounce  of  a  two  per  cent,  solution  of 
cocaine  injected  into  hydrocele  and  allowed  to  stay  about  a  minute  is  said  to  have 
caused  death  (Paul  Berger28).  O.  H.  Garland,29  death  said  to  have  been  produced 
by  the  application  of  twenty  drops  of  a  five  per  cent,  solution  to  the  gum.  E. 
Pfister,30  death  caused  by  an  unknown  quantity  of  a  twenty  per  cent,  cocaine  solu- 
tion injected  into  the  urethra. 

On  the  other  hand,  large  amounts  of  the  drug  have  been  recovered 
from. 

Von  Ploss st  reports  twenty-two  grains  taken  by  an  apothecary,  by  the  stomach, 
with  spontaneous  recovery,  although  the  urine  was  suppressed  for  twenty-four 
hours.  In  another  case  ten  grains  taken  hypodermically  in  the  course  of  five  hours 
produced  complete  unconsciousness,  excessive  failure  of  circulation,  slow  respira- 
tion, recovery  under  treatment  (J.  S.  Spear M)  ;  E.  Caldwell35  reports  recovery 
after  the  hypodermic  injection  of  five  grains,  which  produced  convulsions  with 
asphyxia.  A  case  reported  by  W.  Finlay 34  is  interesting,  because  six  grains  given 
hypodermically  to  a  pregnant  woman  lowered  the  pulse  to  38  and  the  breathing  to 
5,  but  did  not  cause  a  miscarriage. 

Some  of  the  most  remarkable  cases  of  poisoning  by  small  quantities  are  those 
reported  by  T.  H.  Burchard,  ten  drops  of  a  four  per  cent,  solution  injected  hypo- 
dermically caused  unconsciousness  and  apparent  death  in  four  minutes ;  Myer- 
hausen,  eight  drops  of  a  two  per  cent,  solution  upon  the  conjunctiva  produced  in 
a  girl  of  twelve  years  violent  symptoms  ;  Kennicott,  a  case  of  violent  symptoms 
produced  by  cocaine  in  hay  fever  ;  George  T.  Stevens,  one  in  which  four  minims  of 
a  three  and  a  half  per  cent,  solution,  given  to  a  strong  man,  produced  violent  con- 
vulsions, followed  by  mania  ;  Grosholz,  three  drops  of  a  four  per  cent,  solution  in 
the  eye  ;  Frost,  one  drop  of  a  one  per  cent,  solution  in  the  eye  produced  in  a  child 
of  fourteen  marked  poisoning  ;  Ramsden  Wood"  reports  violent  poisoning  with  four 
minims  of  a  twenty  per  cent,  solution.  A  number  of  cases  are  on  record  in  which 
very  severe  symptoms  have  been  produced  by  one  grain  given  hypodermically 
(see  Mattison,  Addinsell,36  and  Pitts")  ;  and  it  is  plain  that,  although  this  dose  has 
been  used  to  a  considerable  extent,  its  employment  is  unjustifiable.  The  occasional 
effects  of  the  local  application  of  cocaine  are  very  remarkable.* 

It  is  not  safe  to  put  upon  mucous  membranes  amounts  which  if  given 
hypodermically  would  be  dangerous  ;  so  that  not  more  than  three-quarters 
of  a  grain  should  be  used  locally. 

*  In  addition  to  cases  mentioned,  see  Brit.  Med.  Journ.,  Nov.,  1885;  Deutsch.  Med. 
Wochensch.,  No.  46,  1886;  New  York  Med.  Rec.,  1886,  ii. ;  La  Pratique  Med.,  Jan.  1891 ; 
S.  J.,  cclvii.  201. 


DELIRIFACIENTS.  209 

The  treatment  of  cocaine-poisoning  must  be  largely  symptomatic. 
When  there  is  great  cerebral  and  motor  excitement,  we  have  found  chloro- 
form to  act  very  happily.  Partial  anaesthesia  may  be  maintained  for  some 
moments.  If  the  symptoms  do  not  yield  to  such  medication,  chloral  may 
be  cautiously  exhibited.  When  .the  toxic  manifestations  are  syncopal, 
hypodermic  injections  of  digitalis  may  be  given,  whilst  alcohol  and  am- 
monia are  exhibited  by  the  mouth  ;  if  circumstances  favor,  intravenous 
injections  of  ammonia  might  be  justifiable.  In  some  cases  life  has  been 
apparently  saved  by  artificial  respiration.  Intravenous  injection  of  salt 
solution  has  been  recommended.* 

Cases  of  cocainismus  or  chronic  cocaine  habit  are  not  rare,  but  in  the 
great  majority  of  instances  the  victim  is  addicted  to  the  use  of  more  than 
one  narcotic.  Usually  the  cocaine  has  been  taken  as  a  substitute  for,  or 
aid  to,  morphine  :  in  a  number  of  cases  the  habit  has  been  formed  by  the 
local  use  of  the  drug  for  hay  fever.  The  symptoms  are  in  no  way  char- 
acteristic ;  dreaminess,  apparent  inability  to  attend  to  the  ordinary  duties 
of  life,  loss  of  reliability,  promptness,  and  punctuality,  varying  mental 
aberration  suggesting,  but  different  from,  that  of  paranoia,  occurring  in 
any  case,  should  arouse  suspicion.  The  paranoiac,  unless  greatly  de- 
pressed, is  usually  egotistical,  self-reliant,  conceited  ;  the  victim  of  co- 
cainism,  in  matters  not  connected  with  his  habit,  is  usually  even  less  self- 
assertive  and  more  easily  led  than  the  normal  individual.  Magnam 58 
affirms  that  a  peculiar  hallucination  as  to  the  existence  of  foreign  bodies 
under  the  skin  is  characteristic. 

The  will  and  the  desire  to  reform  are  as  weak  as  in  the  opium  habit, 
and  the  greatest  difficulty  is  usually  to  get  the  victim  earnestly  to  desire 
reformation.  The  abrupt  withdrawal  of  the  narcotic  is  probably  always 
safe  ;  thus,  in  a  case  in  which  fifteen  grains  were  taken  hypodermically 
daily,  the  immediate  cessation  of  exhibition  was  followed  by  no  greater 
disturbance  than  diarrhoea,  dyspepsia,  and  nervous  depression,  which 
subsided  in  the  course  of  two  or  three  days.  (For  cases,  see  Grundlach  ** 
and  Mattison.26) 

REFERENCES. 

ATROPINE.  8.  WOOD A.  J.  M.  S.,  April,  1873. 

1.  LEFORT L'Union  M6d.,  Nov.  1871.  9.  ALBERTONI    .  .   .  A.  E.  P.  P.,  xv.  265. 

2.  ZELLER V.  A.  P.  A.,  Ixvi.  384.  10.  BOTKIN V.  A.  P.  A.,  xxiv.  85. 

3.  FUBINI  and  BONANNI  .  U.  N.  M.  T.,  1892,  xiv.  n.  MEURIOT    .   .   .   .  De    la    Methode    Physiol. 

4.  BEZOLD  and  BLOEBAUM  .  U.  P.  L.  W.,  i.  en    Th&rap.    et    de   ses 

5.  LANGENDORFF     .  A.  G.  P.,  1886.  Applic.  a  1'Etude  de  la 

6.  GNAUCK Verhandl.   Physiolog.  Ge-  Belladone,  Paris,  1868. 

sellschaft,  Berlin,  1881.  12.  ERASER Tr.   R.  S.  Ed.,  1869,  xxv. 

7.  BEYER A.  J.  M.  S.,  July,  1885.  450. 

*  Systemic  Lavage  for  Poisons. — Intravenous  injection  of  normal  saline  solution  as 
a  treatment  for  acute  poisoning  has  been  experimented  upon  by  Carlo  Bozza  ( Canadian 
Pract.,  1898,  xxiii.),  who  believes  that  it  leads  to  rapid  elimination  and  slow  absorption, 
owing  to  fulness  of  the  blood-vessels.  He  determined  that  the  minimum  fatal  dose  of 
cocaine  given  to  dogs  hypodermically  is  0.025  gramme  per  kilo ;  rising  to  0.03  if  hypo- 
dermoclysis  is  employed,  and  to  0.035  with  lavage  of  the  organism. 

14 


210 


GENERAL  REMEDIES. 


KEUCHEL    ....  In.  Dis.,  Dorpat,  if- 
OTT N.  Y.  M.J.,  1883. 


REFERENCES.— Continued. 

4.  HEILMANN    . 


WOOD J.  P.,  1892. 

HEUBACH    .   .   .   .  A.  E.  P.  P.,  viii. 

ORLOWSKI  ....  Thesis,  Warschau,  1891. 

VOLLMER   .   .   .   .  A.  E.  P.  P.,  xxx. 

UNVERRICHT    .  .  B.  K.  W.,  1896. 

WALTI A.  E.  P.  P.,  1895,  xxxvi. 

HARLEY The  Old  Vegetable  Neu- 
rotics, London,  1869. 

OTT  and  COLLMAR  .  T.  G.,  Aug.  1887. 

JONES M.  T.  G.,  1857. 

ROLLETT    ....  A.  Op.,  xv.  i. 

DIEGEL Arch.  f.  Mikros.  Anat., 

1870,  vi.  i. 

26.  BONDERS    ....  Accommodation    and    Re- 

fraction, New  Sydney 
Soc-  Ed.,  584. 

27.  A.  G.  P.,  xxvi.  460. 

28.  BERNARD    ....  Physiol.  et  Pathologic  du 

Systeme  Nerveux,  Paris, 
ii.  212. 

29.  WOOD P.  M.  T.,  i.  290. 

30.  HOPPE Die  Nervenwirkungen  der 

Heilmittel,  Leipsic,  1856, 
ii.  179. 

31.  VALENTIN  .  .   .  .  Versuch  einer  physiol.  Pa- 

thologic der  Nerven, 
Leipsic,  1864,  ii.  368. 

32.  BORELLI Ed.  M.  J.,  Nov.  1871. 

33.  VON  CARION  .   .   .  Der    intraoculare     Druck 

und  die  Innervations 
Verhaltnisse  der  Iris, 
Vienna,  1868. 

ENGELHARDT   .   .  U.  P.  L.  W.,  ii.  321. 

ROSSBACH  and  FROHLICH  .  Pharmak.  Unter- 
such,  Wiirzburg,  i.  6. 

DA  COSTA   ....  P.  M.  T.,  Feb.  15,  1871. 

HAMMERBACHER  .  A.  G.  P.,  xxxiii.  228. 

NORRIS A.  J.  M.  S.,  Oct.  1862. 

M.  T.  G.,  Nov.  1856. 
London     Pharm.    Journ., 
1871. 

41.  MOREL Ann.  de  la  Soc.  de  Med. 

de  Gand,  1873. 

42.  W.  G.  H.,  Feb.  1845. 

43.  CHAMBERS     .  .  .  Lancet,  1864. 

44.  REICHERT  ....  P.  M.  J.,  Jan.  1901. 

45.  MATHEWS  .  .   .  .  A.  J.  P.,  1901,  iv.  482. 

46.  STRACHAM     .  .   .  L.  L.,  1901,  i. 

47.  RAPHAEL    .  .   .   .  D.  M.  W.,  1899,  xxv.  , 

48.  WIECHOWSKI    .   .  A.  E.  P.  P.,  1901,  xlvi. 

49.  SCHULTZ     ....  A.  A.  P.,  1898. 

HOMATROPINE. 

i.  DE  SCHWEINITZ  and  HARE  .  M.  News,  1887, 
Ii.  731. 

STRAMONIUM. 

i.  LAURENT  .  .  .  .  De  1'Hyoscyamine  et  de 
la  Daturine,  Paris,  1870, 
Thesis. 

HYOSCYAMUS. 

i.  HARLEY The  Old  Vegetable  Neu- 
rotics. 

a.  LAURENT    ....  Thesis,  Paris,  1870. 
3.  SCHROFF    ....  Wb.  G.  A.  W.,  1865. 


5.  SHAW    .   . 

6.  RICHTER 
7.,  RINGER    . 


1.  WOOD,  JR.  . 

2.  WILCOX  . 


.  .  .  Beitr.  zur  Kenntniss  der 
Physiol.  Wirk.  d.  Hyos- 
cyamins,  Jena,  1873. 

.    .    .  J.  N.  M.  D.,  vii.  27. 

.    .    .  N.  Cb.,  i.  294. 

.   .   .  Pract.,  March,  1877. 
Lancet,  1879,  i.  474. 

SCOPOLA. 

.    .    .  T.  G.,  April  15,  1901. 
.    .    .  M.  News,  Aug.  31,  1901. 

HYOSCINE. 


1.  WETHERILL  .   .   .  T.  G.,i.  199. 

2.  WOOD  ......  T.  G.,Jan.  18 

3.  GLEY  and  RONDEAU  .  C.  R.  S.  B.,  1887.  iv.  56. 

4.  BALAGOPAL 

5.  WINNETT   . 


Indian  Med.  Rec.,  1894. 
West.  Med.  Rev.,  1898,  iii. 

2IO. 

A.  and  N.,  iii.  539. 
U.  M.  M.,  i. 


6.  HUTCHINSON 

7.  CAREY 

8.  O'HARA  .....  T.  G.,  ii. 

9.  ROOT     ......  T.  G.,  ii. 

10.  WOOD  ......  Amer.  Med.  1905. 

11.  MAIRET  and  COMBEMALE  .  C.  R.  S.  B.  1887. 

12.  KOCHMANN    .  .  .  Ther.  Geg.  1903,  v,  202. 

13.  CLAUSSENS    .  .  .  M.  Dis.  1883. 

14.  KOBERT  .....  A.  E.  P.  P.  1887. 

CANNABIS  IND1CA. 

1.  WOOD  ......  Proc.     Amer.     Philosoph. 

Soc.,  1869,  xi.  226. 

2.  LAWRIE  .....  Stille's  Therap.,  i.  772. 

3.  ZEITLER  .....  In.  Dis.,  1885. 

4.  HARE   ......  T.  G.,  1887. 

5.  FRAENKEL     .   .   .  A.  E.  P.  P.,  1903,  xlix. 


COCAINE. 


KOLLER  .  .  , 
BOSWORTH  . 
FEINBERG  .  , 
ARLOING  .  . 
ALBERTONI  , 
DANILEWSKY 


.  W.  M.  W.,  Nov.  1884. 
.  N.  Y.  M.  R.,  Nov.  15,  1884. 
.  B.  K.  W.,  March,  1887. 
.  Lyon  M.,  May,  1883. 
.  A.  G.  P.,  1890,  xlviii. 
.  A.  G.  P.,  1892,  Ii. 
MORENO  Y  MAIZ  .  Thesis,  Paris,  1868. 

BIBRA Die  Narkot.  Genussmittel, 

1855- 
VON  ANREP  .   .   .  A.  G.  P.,  1880,  xxi. 

TUMASS A.  E.  P.  P.,  xxii. 

Mosso A.  G.  P.,  1890,  557. 

ALMS A.  Ph.,  1886,  Suppl. 

POPIELSKI  ....  Cb.  P.,  1896,  x. 
REICHERT.   .   .   .  Am.  Lan.,  May,  1891. 
BERTHOLD  .  .  .   .  C.  M.  W.,  1885,  435. 

BEYER A.  J.  M.  S.,  July,  1885. 

PACHON  and  MOULINIER  .  C.  R.  S.  B.,  1898,  v. 
DURDUFI     .   .   .   .  D.  M.  W.,  1887,  172. 
EISENMENGER  .   .  Pflanzenstoffe,  2d  ed.,  885. 
U.  N.  M.  T.,  xvi.  170. 
J.  A.M.  A.,  July,  1887. 
B.  M.  S.  J.,  Sept.  1882. 
A.  E.  P.  P.,  xxx. 
T.  G.,  1888. 
D.  M.  W.,  1883,  ix.  50. 
Med.  R.,  1887,  i. 


BENEDICENTI  , 
BIGNON  .  .  .  . 
MASON  .  .  .  . 
LIMBOURG  .  . 
DUNN  .  .  .  .  . 
ASCHENBRAIDT 
MATTISON 


SIMES M.  News, 


DELIRIFACIENTS. 


211 


REFERENCES.— Continued. 


28.  BERGER   .  . 

29.  GARLAND    . 

30.  PFISTER  .   . 

31.  VON  PLOSS 


32.  SPEAR  .   .   . 

33.  CALDWELL 

34.  FINLAY   .  . 

35.  WOOD  .   .   . 

36.  ADDINSELL 


.  B.  M.  S.  C.  P.,  1891,  xvii. 

Lancet,  Nov.  1895. 

B.  K.  W.,  1896,  xxxiii. 

Husemann's         Pflanzen- 

stoffe,  2d  ed. 
.  N.  Y.  M.  R.,  1885. 
.  B.  M.  J.,  1885. 
,  Aus.  M.  Gaz.,  1887,  ii. 
.  Aus.  M.  Gaz.,  Aug.  1886. 
.  Lancet,  1888,  i. 


37.  PITTS Lancet,  1887,  ii. 

38.  MAGNAM    .   .   .  .  N.  C.,  1896,  15. 

39.  GRUNDLACH  .  .   .  S.  Jb.,  1886,  ccxii. 

40.  VEREBELY   and    HORV/TH  .  Cb.    N.,    1899, 

xviii. 

41.  DADD L.  S.,  1899. 

42.  WIECHOWSKI    .   .  A.  E.  P.  P.,  1901,  xlvi. 

43.  GLASENAP  ....  In.   Dis.,   St.    Petersburg, 


44.  REICHEKT 


.  P.  M.  J.,  1902. 


FAMILY   V.— EXCITO-MOTORS. 


IN  this  class  are  included  such  drugs  as  increase  the  reflex  activity  of 
the  spinal  centres,  and  thereby  give  rise  to  disturbance  of  motility.  The 
only  representatives  of  the  class  used  by  the  practitioner  of  medicine  are 
those  drugs  which  contain  strychnine  as  their  active  principle. 

NUX    VOMICA— NUX    VOMICA.     U.S. 

The  seeds  of  Strychnos  Nux-vomica,  a  middle-sized  tree  growing  in 
the  East  Indies,  whence  the  drug  enters  commerce.  They^re  circular, 
nearly  flat  disks,  a  little  less  than  an  inch  in  diameter,  covered  with  very 
short,  satin-like,  grayish  hairs  ;  internally  they  are  tough  and  horny,  and 
are  possessed  of  an  intensely  bitter  taste.  They  contain  two  alkaloids, 
— strychnine  and  brucine, — existing  in  combination  with  an  acid,  the  so- 
called  igasuric  of  Pelletier  and  Caventou,  which,  according  to  Huse- 
mann,  is  identical  with  malic  acid. 

The  U.  S.  Pharmacopoeia  recognizes  the  extract  (EXTRACTUM  Nucis 
VOMICA),  of  which  the  dose  is  one-fourth  of  a  grain  (0.016  Gm.), 
equivalent  to  about  one-twenty-seventh  of  a  grain  of  total  alkaloids  ;  the 
tincture  (TiNCTURA  Nucis  VOMICA,  U.  S. ),  ten  per  cent.;  dose,  from 
ten  to  fifteen  minims  (0.60—0.90  C.c. ),  fifteen  to  twenty-five  drops  ;  and 
the  fluid  extract  (FLUIDEXTRACTUM  Nucis  VOMICA),  which  is  required 
to  assay  one  gramme  of  strychnine  (not  total  alkaloids)  one  hundred 
cubic  centimetres;  dose,  three  minims  (o.  18  C.c.),  containing  about  one- 
twenty-third  of  a  grain  of  alkaloids.  It  is  usually  estimated  that  strych- 
nine constitutes  about  forty  per  cent,  of  the  alkaloids.  Practically  there 
is  no  qualitative  difference  between  the  medical  action  of  strychnine  and 
that  of  the  cruder  preparations  of  nux  vomica,  over  which  it  usually 
should  have  the  preference  on  account  of  definiteness  of  action. 

STRYCHNINA.     U.S. 

As  kept  in  the  shops,  strychnine  is  a  grayish-white  powder,  but  by 
slow  crystallization  from  its  alcoholic  solution  it  may  be  obtained  in 
octahedral  or  quadrilateral  prisms.  It  is  so  bitter  that  it  will  impart  a 
very  intense  bitter  taste  to  twenty  thousand  times  its  weight  of  water. 
On  account  of  its  insolubility  (one  in  about  seven  thousand  parts  of 
cold  water)  it  is  very  rarely  used  in  medicine,  at  least  in  the  United 
States,  the  sulphate  (STRYCHNINE  SULPHAS,  U.  S. )  being  universally 


EXCITO-MOTORS.  213 

preferred,  and  being  what  is  commonly  meant  in  American  writings 
when  the  word  ' '  strychnine' '  is  used.  Strychnine  sulphate  contains 
about  seventy-five  per  cent,  of  strychnine.  The  ordinary  dose  is  from 
one-fortieth  to  one-twentieth  of  a  grain  (0.0016-0.0032  Gm.  ).* 

PHYSIOLOGICAL  ACTION. — Local  Action. — The  local  action  of  strych- 
nine is  that  of  a  very  feeble  irritant ;  upon  the  mucous  membrane  of  the 
stomach  it  acts  like  a  simple  bitter. 

Absorption  and  Elimination. — Strychnine  is  absorbed  rapidly,  whether 
taken  by  the  mouth  or  by  hypodermic  injection. 

Several  investigators  have  attempted  to  determine  the  comparative  rate  of  ab- 
sorption of  strychnine  in  different  portions  of  the  alimentary  canal  by  isolating  these 
different  portions  by  ligatures  and  then  injecting  strychnine  into  them.  After  tying 
of  the  pylorus,  Bouley  and  Colin J  found  that  the  absorption  of  strychnine  was  rapid 
in  the  stomachs  of  dogs  and  cats,  whilst  Tappeiner  determined  that  in  cats  it  was 
taken  up  very  slowly.  In  two  series  of  experiments,  S.  J.  Meltzer 2  found  that,  after 
tying  the  cardiac  and  pyloric  ends  of  the  stomach,  large  doses  of  strychnine  would 
remain  in  the  stomach  of  the  rabbit  without  producing  any  physiological  effect, 
whilst  under  similar  circumstances  in  the  dog  the  gastric  absorption  was  extremely 
slow  and  uncertain.  Meltzer  further  determined  that  absorption  takes  place  in  the 
oesophagus  somewhat  more  rapidly  than  in  the  stomach,  whilst  the  alkaloid  was 
taken  up  with  great  and  about  equal  avidity  in  the  small  intestines,  colon,  and  rec- 
tum. Although  the  method  of  investigation  is  open  to  the  objection  that  the  oper- 
ative procedure  may  seriously  disturb  the  mucous  membrane  of  the  part,  and 
consequently  its  absorbing  power,  it  is  probable  that  the  results  of  Meltzer  are  sub- 
stantially correct. 

Strychnine  has  been  detected  by  chemists  in  the  blood,  kidney,  liver, 
heart,  brain,  spinal  cord  ;  indeed,  practically  in  all  portions  of  the  system. 
The  statement  of  R.  W.  Lovett,3  that  it  accumulates  in  the  spinal  cord, 
has  been  disproved  by  Ipsen  and  by  Lesser.*  It  may  be  in  excess  in  the 
organs  concerned  with  absorption  and  elimination,  as  in  the  stomach, 
liver,  f  and  kidneys,  but  seems  to  be  nowhere  else  present  in  the  body 
of  the  poisoned  animal  or  man  out  of  proportion  to  the  amount  of  blood 
going  to  the  organ. 

It  is  certain  that  strychnine  escapes  from  the  body  to  some  extent 
unchanged,  as  it  has  been  found  in  the  urine  by  Peter  von  Rautenfeld,5 
by  Wormley,6  by  Schauenstein,  by  Kratter,7  and  by  Dixon  Mann.  Its 
elimination  is  prompt  and  rapid,  as  Ipsen  asserts  that  it  can  be  detected  in 

*  Thoinot  and  Brouardel  (La  Presse  Med.,  1898,  i.,  Annex,  127)  found  that  when  strych- 
nine is  macerated  with  the  spinal  cord  and  brain,  or  with  potato  starch,  the  toxicity  is  so 
far  lost  that  double  the  ordinary  fatal  dose  of  the  alkaloid  is  required  to  kill  guinea-pigs. 
When  the  nerve-tissue  mixture  was  filtered,  the  filtrate  was  without  toxic  action.  The 
strychnine  could,  however,  be  recovered  from  any  of  the  mixtures,  and  when  separated 
was  found  to  be  physiologically  active.  The  loss  of  toxicity  is  therefore  not  due  to  its 
destruction.  The  authors  believe  that  the  loss  of  activity  is  due  to  the  strychnine  being 
so  fixed  as  to  interfere  with  its  absorption.  Talc  and  charcoal  were  found  to  have  the 
same  properties  as  nerve-tissue  to  a  slight  degree. 

t  Scruff  and  Lautenbach  believe  that  they  have  proved  that  the  alkaloid  is  destroyed, 
at  least  in  part,  in  the  liver ;  a  conclusion  which  is  strongly  combated  by  Chouppe  and 
Pinet  (Compt.-Rend.  Soc.  Biol.,  1887,  cv.),  and  is  very  doubtful. 


2i4  GENERAL  REMEDIES. 

the  urine  five  minutes  after  its  absorption,  and  others  have  detected  it  in 
the  urine  half  an  hour  after  its  exhibition  ;  and  in  various  poisoning  cases, 
fatal  within  two  hours,  it  has  been  found  in  the  urine.  Kratter  and  Mann 
believe  that  they  have  proved  that  the  elimination  is  complete  within 
forty-eight  hours.  According  to  P.  C.  Plugge,8  a  portion  of  the  alkaloid 
is  converted  into  strychnic  acid* 

General  Action. — According  to  the  experiments  of  Borzi,9  strychnine 
paralyzes  the  sensory  organs  of  plants,  but  increases  the  tension  (motor 
function)  of  the  plants  :  solutions  as  low  as  I  in  10,000  acted  distinctly 
upon  vegetable  protoplasm,  and  when  the  plant  was  apparently  killed  by 
strychnine,  chloroform  or  paraldehyde  would  restore  its  functional  activity. 

Upon  all  animals  strychnine  probably  acts  similarly,  but  with  great 
variations  of  power. 

According  to  Leu  be,10  it  takes  ten  times  as  much  strychnine  to  kill  chickens 
as  it  does  to  kill  other  birds,  weight  for  weight ;  and  among  mammals  the  guinea- 
pig  is  very  insensitive  to  it.  It  has  also  been  asserted  that  on  some  monkeys  it  has 
but  little  influence  (Boston  Med.  and  Surg.  Journ. ,  1872).  Very  young  animals 
are  said  to  be  quite  insensitive  to  it.f  The  resistance  of  birds  to  the  poison  is 
attributed  by  Falck  u  partially  to  slow  absorption  and  partially  to  a  destruction  of 
the  poison  in  the  body. 

When  taken  in  quantities  just  sufficient  to  produce  sensible  physio- 
logical effects,  strychnine  in  man  induces  a  feeling  of  restlessness,  per- 
haps accompanied  by  tremblings  in  the  limbs  and  some  stiffness  in  the 
neck  and  jaws.  When  a  somewhat  larger  amount  has  been  given,  there 
may  be  general  muscular  twitchings  and  startings,  with  stiffness  and 
stricture  of  the  throat  and  chest ;  formications  or  other  abnormal  sen- 
sations under  the  skin  may  or  may  not  be  present.  After  poisonous 
doses  the  symptoms  come  on  usually  in  from  fifteen  to  twenty  minutes, 
rarely  after  an  hour,  with  great  suddenness  ;  sometimes  the  convulsions 
are  preceded  by  partial  spasms  of  the  muscles  of  the  extremities,  but 
more  often  the  patient  is  suddenly  thrown  down  by  a  general  tetanic 
spasm.  In  this  the  body  is  bent  backward  and  rests  upon  the  heels 
and  the  head,  in  a  condition  of  opisthotonos ;  the  legs  are  rigidly  ex- 
tended and  the  feet  everted  ;  the  arms  bent  and  the  hands  clinched  ; 
the  eyes  staring,  wide  open  ;  the  corners  of  the  mouth  often  drawn  up  so 
as  to  produce  the  risus  sardonicus.  The  senses  may  be  sharpened,  but 
ringing  in  the  ears  and  dimness  of  vision  may  be  induced  if  the  fits  are 
severe.  The  face  is  at  first  pale,  but,  if  the  fit  be  sufficiently  severe  and 
protracted,  it  becomes  livid  from  the  interference  with  respiration.  Con- 
sciousness is  not  affected,  unless  when  asphyxia  becomes  so  pronounced 
as  to  threaten  death  ;  in  such  cases  sometimes  a  period  of  insensibility 

*  The  theory  that  strychnine  becomes  fixed  in  certain  tissues  of  the  body,  originally 
proposed  by  Widal  and  Nobecourt,  has  received  considerable  credence,  but  its  correctness 
has  certainly  not  been  proven.  For  discussion  of  the  whole  subject,  with  experiments  and 
literature,  see  paper  of  S.  J.  Meltzer  and  G.  Langmann.50 

t  See  Arch.f.  Ges.  Physiol.,  1884,  xxiv.  530;  also  Behrend  Lau  (Elmshorn  Inaug. 
Diss.,  1886). 


EXCITO-MOTORS.  215 

precedes  dissolution,  but  generally  the  intellect  is  clear  to  the  moment  of 
death  The  muscles  of  the  jaw  are  usually  the  last  in  the  body  to  be 
affected,  but  trismus  finally  comes  on  in  severe  cases.  We  have  seen 
death  occur  in  this  first  convulsion  in  animals  ;  but  Tardieu  states  that  he 
knows  of  no  such  instance  in  man  (compare  case  of  Demme  n).  After  a 
time  the  paroxysm  is  at  an  end,  the  jaw  drops,  the  muscles  relax,  and  a 
period  of  calm  comes  on,  to  be  succeeded  by  a  second  convulsion  like 
the  first.  These  convulsions  are  excited  by  the  slightest  touch,  by  a 
draught  or  breath  of  air,  even  by  a  loud  sound  ;  but  a  firm  grasp  or  hard 
rubbing  of  the  muscles  is  frequently  grateful.  A  slight  rigidity  is  some- 
times manifest  between  the  paroxysms,  but  no  marked  stiffness.  The 
spasms  are  generally,  but  not  always,  very  painful.  There  are  often 
erections  of  the  penis,  and  the  faeces  and  urine  may  be  passed  involun- 
tarily. If  the  case  terminates  favorably,  the  convulsions  gradually  lessen 
in  intensity,  and  fade  away,  leaving  the  patient  exhausted,  with  a  sore, 
tired  feeling  in  the  muscles.  After  death,  post-mortem  rigidity  is  devel- 
oped very  quickly.  Autopsies  have  revealed  nothing  but  the  usual  con- 
gestive lesions  of  death  from  asphyxia,  and,  at  times,  indications  of  spinal 
hyperaemia. 

Cerebrum. — So  far  as  our  present  knowledge  goes,  strychnine  has 
little  or  no  influence  upon  the  cerebral  cortical  centres.  The  stimulation 
of  the  special  senses  sometimes  seen  in  the  beginning  of  strychnine-poi- 
soning is  probably,  though  not  certainly,  peripheral  in  its  origin  ;  and 
consciousness  is  probably  never  directly  affected  by  the  drug. 

Spinal  Cord. — The  spinal  origin  of  the  convulsions  of  strychnine  has 
been  demonstrated  by  a  large  number  of  experimenters.  They  occur  after 
section  of  the  spinal  cord  below  the  point  of  division.  In  Brown- Se"quard's 
experiments,  confirmed  by  Martin-Magron  and  Buisson,  when  the  spinal 
cord  was  severed  just  below  the  origin  of  the  nerve  supplying  the  fore 
legs  of  the  frog,  and  the  lower  section  of  the  cord  isolated  by  cutting 
its  blood-vessels,  strychnine  produced  convulsions  in  the  anterior  part 
of  the  body,  whilst  the  posterior  segment  of  the  body  was  quiet  and  re- 
tained its  normal  reflexes,  although  the  blood  was  carrying  strychnine 
to  every  part  of  it  except  the  spinal  cord.  It  has  been  proved  by 
Van  Deen,  by  Valentin,  and  by  A.  J.  Spence  *  that  when  strychnine  is 
placed  upon  the  cut  upper  surface  of  the  brain  or  spinal  cord  so  that  it 
will  diffuse  itself  within  the  spinal  cord  without  being  carried  by  the  cir- 
culation, convulsions  appear  in  those  muscles  whose  nerves  have  their 
origin  near  the  point  of  application,  and  spread  from  muscle  to  muscle 
as  the  poison  creeps  through  the  cord.  The  accuracy  of  the  statement 

*  Some  of  the  phenomena  stated  by  Spence  to  have  occurred  are  at  present  very  diffi- 
cult to  explain.  Thus,  he  noted  that  as  the  poison  travelled  down  the  cord  there  was  a 
time  when  irritation  of  the  fore  feet  caused  only  spasm  in  them  ;  later  in  the  experiment, 
irritation  of  the  front  feet  caused  spasm  of  both  the  front  and  hind  feet,  although  irrita- 
tion of  the  latter  did  not  produce  other  than  normal  reflex  movements  ;  later  still  in  the 
poisoning  came  a  stage  when  irritation  of  the  front  legs  was  powerless  to  cause  spasm  in 
the  hind  legs,  although  irritation  of  the  latter  would  now  cause  spasm  in  the  former. 


216  GENERAL  REMEDIES. 

of  Claude  Bernard,12  that  when  all  the  posterior  nerve-roots  are  cut  no 
convulsions  occur,  whereas,  if  a  single  afferent  root  remains,  irritation  of 
its  nerve  will  cause  general  tetanic  spasm,  has  been  denied  by  Spitzka, 
but  is  probably  correct.  If  so,  it  demonstrates  that  the  reflex  motor  gan- 
glionic  cells  are  incapable  of  originating  an  impulse,  and  in  strychnine- 
poisoning  are  simply  in  such  a  condition  of  over-excitability  as  renders 
them  exceedingly  sensitive  to  slight  irritations  and  causes  them  to  re- 
spond most  energetically  to  the  feeblest  stimulus,  the  convulsion  always 
being  therefore  a  reflex  phenomenon. 

That  the  action  of  the  alkaloid  is  upon  the  motor  centres  of  the  cord 
seems  further  to  be  demonstrated  by  the  ingenious  experiments  of  Van 
Deen,13  who  so  divided  all  the  tissues  that  the  anterior  portion  of  an 
eviscerated  frog  was  connected  with  the  posterior  solely  by  the  posterior 
columns  of  the  cord.  When  one  or  two  drops  of  a  solution  of  strych- 
nine were  placed  in  the  mouth  of  the  prepared  batrachian,  tetanus,  con- 
fined to  the  anterior  segment  of  the  body,  was  developed  ;  and  it  was 
also  found  that  while  irritation  of  the  posterior  feet  caused  in  them  only 
ordinary  reflex  movements,  in  the  front  legs  tetanic  spasms  were  simul- 
taneously induced. 

Strychnine  is  evidently  a  powerful  stimulant  to  the  motor  cells  of  the 
whole  spinal  tract  up  to  the  pons  Varolii.  Hare48  found  demonstrable 
histological  changes  in  the  cells  of  the  anterior  cornua.  Biernacki14 
believes  that  the  cortical  portion  of  the  pyramidal  or  motor  tract  does  not 
share  in  the  stimulation,  because  he  has  found  that  in  the  strychnized 
rabbit  the  psycho-motor  centres  in  the  brain  are  even  less  susceptible  to 
stimulation  than  in  the  normal  animal. 

Motor  Nerves. — After  death  from  strychnine,  the  functions  of  the 
motor  nerves  are  always  found  to  be  more  or  less  impaired,  so  that  gal- 
vanization of  the  nerve-trunk  produces  either  very  feeble  contractions  in 
the  tributary  muscles  or  none  at  all.* 

That  the  exhaustion  produced  by  the  excessive  number  of  violent 
impulses  which  travel  along  the  motor  nerves  during  the  period  of  strych- 
nic  convulsions  is  a  distinct  factor  in  causing  the  loss  of  functional  power 
in  the  nerve-trunk  was  proved  in  1856  by  Kolliker,15  who  found  that  when 
he  cut  the  sciatic  nerve  in  the  frog  and  exhibited  strychnine  the  divided 
nerve  would  respond  to  galvanic  stimulation  after  all  functional  power 
had  been  lost  in  the  nerve  whose  connection  with  the  centres  was  intact. 

*  See  Matteucci  (  Traitt  des  Phenomenes  electro-physiologiques,  Paris,  1844),  Moreau 
(Comptes-Rendus  Soc.  de  Biol.,  1855),  M.  Ambrosoli  (Gazette  Medicate,  1857,  525),  Wit- 
tich  (Bericht  d.  Fortschritte  d.  Anat.,  1857,  434),  Kolliker  (  Virc how's  Archiv,  1856,  x. 
239),  and  Vulpian  (Archives  de  Physiologic,  Nov.  1870,  125).  The  statement  of  W.  H. 
Klapp,  that  he  has  found  in  thirty-seven  experiments  the  motor  nerve  unimpaired  in  the 
frog  after  death  from  strychnine  (Journ.  Ment.  and  Nerv.  Dis.,  Oct.  1878),  may  depend 
upon  the  fact  that  in  some  species  of  frogs  the  nerves  are  extraordinarily  refractory  to  the 
action  of  strychnine,  or  it  may  be  that  he  employed  such  powerful  stimuli  that  all  appar- 
ent differences  were  lost.  Sautesson  found  that  strychnine  acts  twelve  times  more 
powerfully  upon  the  nerves  of  Rana  esculenta  than  upon  those  of  JR.  temporaria.  S. 
Leduc  believes  that  he  has  demonstrated  that  strychnine  can  be  electrolytically  carried 
into  a  human  nerve  and  temporarily  suspend  its  functional  power  ( C.  R.  S.  B.,  1902,  liv.). 


EXCITO-MOTORS.  217 

These  experiments  have  been  confirmed  by  Martin-Magron  and  Buisson, 
and  must  be  accepted.  Nevertheless,  it  has  been  demonstrated  by  Vul- 
pian,  by  E.  Poulson,16  by  C.  G.  Sautesson,"  and  others,  that  strych- 
nine has  a  direct  paralyzing  action  upon  the  peripheral  motor  nerves. 
When  the  nerve  has  been  divided,  as  in  the  experiments  of  Kolliker, 
it  finally  becomes  paralyzed  in  strychnine- poisoning  ;  and  Vulpian  has 
found  that  if  the  doses  have  been  properly  adjusted  the  motor  nerve 
after  a  time  will  regain  in  the  poisoned  frog  its  activity  before  stimulation 
of  the  spinal  cord  has  altogether  passed  off,  so  that  the  history  of  such  an 
experiment  is,  first,  tetanus, — then  paralysis,  due  to  the  loss  of  power  by 
the  nerve-trunks, — and  then  again  a  tetanus  which  gradually  subsides  into 
the  normal  condition.  Further,  as  pointed  out  by  Richet,  and  as  we 
have  frequently  seen,  if  an  enormous  dose  of  strychnine  be  injected  into 
the  jugular  veins  of  the  dog,  death  immediately  results  practically  without 
convulsion,  it  being  possible  by  artificial  respiration  to  maintain  the  circu- 
lation for  a  considerable  length  of  time.  Under  these  circumstances  the 
motor  nerves  will  be  found  to  have  entirely  lost  their  power  of  responding 
to  galvanic  or  other  stimulation,  although  they  may  still  be  able  to  trans- 
mit sufficient  afferent  impulses  from  the  spinal  cord  to  produce  slight  but 
distinct  choreic  muscular  contractions. 

Sensory  Nerves. — The  afferent  or  sensory  nerves  appear  not  to  be 
affected  by  strychnine.  Martin-Magron  and  Buisson  having  tied  all  the 
tissues  of  a  hind  leg  of  a  frog  except  the  nerve,  and  injected  strychnine 
into  the  body  of  the  batrachian,  found  that  at  a  time  when  convulsions 
had  ceased  in  all  portions  of  the  body  except  the  leg  to  whose  nerve  the 
poison  had  not  had  access,  slight  irritation  of  the  poisoned  foot  would 
induce  tetanic  spasms  in  the  protected  leg,  thus  showing  that  though  the 
motor  nerves  to  which  the  strychnine  had  had  access  were  completely 
paralyzed,  the  afferent  nerves  were  still  functionally  active. 

Circulation. — The  full  dose  of  strychnine  produces  a  rise  of  the  arte- 
rial pressure  which  is  enormously  increased  during  the  convulsion,  after 
which  there  is  a  very  pronounced  fall  in  the  arterial  pressure.*  The  pri- 
mary rise  is  not  due  to  the  convulsion,  since  it  precedes  the  convulsion, 
and  occurs  in  curarized  animals.  It  is  largely  due  to  vaso-motor  con- 
traction, since  Mayer,18  Klapp,19  and  Reichert20  have  all  found  that  after 
paralysis  of  the  dominant  vaso-motor  centres  by  section  of  the  cord,  strych- 
nine causes  no  rise  at  all,f  or  an  exceedingly  slight  one,  of  the  arterial 
pressure.  The  fall  of  the  arterial  pressure  has  been  shown  by  Klapp  and 
Reichert  to  be  due,  in  part  at  least,  to  paralysis  of  the  vaso-motor  centres. 
By  the  intravenous  use  of  very  large  doses  of  strychnine  it  is  possible 

*  See  also  Richter  ( Zeitschrift f.  ration.  Med.,  1863,  xviii.),  Denys  (Arch.f.  Exper. 
Path.  Pharm.,  xx.  306),  Kionka  (Arch,  de  Pharmacod.  interend.,  1898,  v.). 

t  Schlesinger  (loc.  cil.)  found  after  the  division  of  the  cord  that  the  rise  of  arterial 
pressure  caused  by  strychnine  both  absolutely  and  relatively  exceeds  that  produced  in 
the  normal  animal.  This  result  we  believe  to  have  been  due  to  imperfect  section  of  the 
cord.  For  an  elaboration  of  the  reasons  for  this  belief,  see  tenth  edition  of  this  treatise. 


218  GENERAL  REMEDIES. 

to  produce  immediate  paralysis  of  those  centres,  with  corresponding  fall 
of  the  arterial  pressure. 

Our  knowledge  of  the  cardiac  action  of  strychnine  is  still  imperfect. 
Although  Lahousse  believes  that  in  any  dose  strychnine  depresses  the 
intra-cardiac  ganglia,  it  is  probable  that  the  small  dose  has  a  stimulating 
influence  upon  the  heart.  In  the  experiments  of  I.  Steiner,  confirmed  by 
Klapp,  it  was  found  that  strychnine  affected  the  isolated  frog's  heart  much 
more  markedly  when  it  was  placed  upon  the  posterior  than  when  it  was 
placed  upon  the  anterior  face  ;  also  that  it  acted  much  more  promptly  and 
severely  upon  the  separated  sinus  venosus  than  upon  the  separated  ven- 
tricles or  auricles,  leading  to  the  natural  conclusion  that  it  acts  especially 
upon  the  ganglia  of  the  sinus. 

In  regard  to  the  action  of  the  alkaloid  upon  the  vagi  there  is  much 
difference  of  statement  by  investigators.  Carl  Heinemann,  Mayer,  and 
Klapp  all  affirm  that  the  heart  under  the  influence  of  strychnine  can  be 
arrested  by  galvanization  of  the  par  vagum,  but  Martin-Magron  and 
Buisson,  E.  T.  Reichert  and  Lahousse,21  state  that  the  sufficient  dose  of 
strychnine  paralyzes  inhibition.*  Reichert  has  found  that  the  early  effect 
of  strychnine  is  to  stimulate  the  peripheral  inhibitory  apparatus  of  the 
heart,  but  that  if  the  dose  have  been  sufficient  this  stimulation  is  followed 
by  pronounced  depression  or  even  complete  paralysis,  f 

Blood. — Harley  found  that  blood  shaken  for  twenty-four  hours  with 
air  contained  11.33  parts  of  oxygen  and  5.96  parts  of  carbonic  acid; 
while  blood  treated  in  a  precisely  similar  manner,  except  in  the  addition 
of  strychnine,  yielded  17.80  parts  of  oxygen  and  2.73  parts  of  carbonic 
acid.  Kionka 22  found  that  blood  taken  from  the  strychnized  animal  does 
not  absorb  oxygen  with  the  avidity  of  normal  blood,  although  no  spec- 
troscopic  changes  could  be  discovered  in  it.  Moreover,  his  analysis  of 
blood  gases  shows  during  the  dyspnoeic  stage  of  the  poisoning  an  extreme 
lack  of  oxygen  without  any  excess  of  carbonic  acid.  Maurel 33  states  that 
five  centigrammes  of  strychnine  sulphate  are  sufficient  immediately  to  kill 
the  leucocytes  in  one  hundred  grammes  of  blood,  and  that  in  poisoning 
by  strychnine  sulphate  the  death  of  the  leucocytes  and  of  the  animals 
takes  place  at  the  same  time.! 

*  For  the  paper  of  Brunton  and  Cash  showing  that  strychnine  increases  the  "  refrac- 
tory period"  of  the  isolated  frog's  heart,  see  Proc.  Roy.  Soc.,  1883.  A  consideration  of 
this  memoir  would  require  an  elaborate  discussion  of  the  minute  points  of  cardiac  physi- 
ology, and,  as  it  would  throw  at  present  no  light  upon  the  practical  use  of  the  drug,  is  not 
entered  upon. 

t  According  to  Reichert,  when  the  salt  of  strychnine  is  injected  intravenously  into  the 
dog  there  is,  first,  a  transient  increase  in  the  pulse-rate,  due  to  the  immediate  overwhelm- 
ing action  of  the  undistributed  strychnine  upon  the  inhibitory  apparatus  of  the  heart ; 
second,  a  lessening  of  the  pulse-rate,  due  to  slight  stimulation  of  the  pneumogastric  end- 
ings ;  third,  a  marked  increase  in  the  pulse-rate,  due  to  pneumogastric  depression  ;  and, 
finally,  a  decrease  in  the  pulse-rate,  the  result  of  an  influence  upon  the  heart-muscle  or 
its  ganglia.  Reichert  determined  that  five  milligrammes  of  strychnine  per  kilogramme 
of  weight  will  paralyze  the  peripheral  vagi  in  the  dog. 

t  The  statement  of  Carl  Heinemann,  that  the  diminished  frequency  of  cardiac  move- 
ment and  the  diastolic  pauses  taking  place  in  the  heart  of  the  strychnized  frog  occur  after 


EXCITO-MOTORS.  219 

Respiration. — The  injection  of  strychnine  produced  in  the  dog  an  ex- 
traordinary increase  in  the  respiratory  air-movement,  which  in  H.  C. 
Wood' s 24  experiments  never  amounted  to  less  than  seventy-five  per  cent. , 
and  sometimes  rose  to  three  hundred  per  cent.  On  chloralized  dogs  the 
respiratory  effects  of  the  alkaloid  were  even  more  pronounced. 

Strychnine  is  among  the  most  certain  of  the  respiratory  stimulants,  its 
action  upon  the  respiratory  centres  being  evidently  a  portion  of  its  wider 
influence  upon  the  whole  motor  tract. 

Temperature. — We  know  of  no  recorded  temperature-curve  in  human 
poisoning,  but  in  the  lower  animals  there  is  usually  a  primary  elevation  of 
the  temperature  followed  by  a  pronounced  fall,  both  the  rise  and  fall  ap- 
parently being  in  greater  or  less  measure  independent  of  the  convulsions. 

According  to  the  experiments  of  Kionka,  during  both  temperature  periods, 
heat-production,  and  heat-dissipation  are  above  the  normal,  but  during  the  rise  of 
temperature  the  increase  in  heat-production  is  greater  than  the  increase  of  heat- 
dissipation,  whilst  during  the  period  of  falling  temperature  the  overplus  of  heat- 
dissipation  is  greater  than  that  of  heat-production.  Harnack  *9  confirms  the  results 
of  Kionka,  but  has  found  also  that  irregularly  at  any  time  during  the  poisoning  there 
may  be  a  sudden  arrest  of  heat-production  without  corresponding  fall  in  heat-dissi- 
pation, so  that  the  temperature  of  the  animal  rapidly  descends.  Anton  Obermeier  *5 
has  found  that  in  the  rabbit  strychnine  causes  a  notable  increase  in  the  production 
of  carbonic  acid, — i.e.,  of  oxidation  ;  and  U.  Mosso26*  affirms  that  even  in  the  cura- 
rized  dog  a  very  pronounced  rise  of  rectal  temperature  may  be  produced  by 
strychnine.  The  final  fall  of  temperature  is  due  to  the  excessive  dissipation  of  heat, 
which  in  turn  is  probably  the  outcome  of  vaso-motor  paralysis. 

It  would  appear  that  the  action  of  strychnine  upon  heat-production  and 
heat-dissipation  is  independent  of  its  convulsive  influence,  and  is  probably 
the  outcome  of  some  effect  upon  the  central  nerve-system,  but  we  have 
not  sufficient  evidence  to  determinate  the  exact  nature  of  this  influence. 

Eye. — The  effect  of  strychnine  upon  the  normal  eye  has  been  studied 
by  Von  Hippel28  and  Cohn,29  with  rather  different  results.  They  both, 
however,  found  the  sharpness  of  vision  increased. 

SUMMARY. — In  small  therapeutic  dose  strychnine  produces  little 
apparent  effect,  but  acts  as  a  powerful  bitter,  increasing  at  the  same 
time  the  general  tone  of  the  body.  After  large  therapeutic  doses  there 
is  probably  a  pronounced  general  stimulation  and  increase  of  bodily 
tone.  The  fullest  permissible  doses  stimulate  very  powerfully  the  respi- 
ratory centres,  and  also  slightly  increase  blood-pressure  by  stimulation 
of  the  vaso-motor  centres,  and  probably  also  of  the  heart  itself.  Toxic 
cases  produce  violent  reflex  tetanic  convulsions,  -without  loss  of  con- 
sciousness, by  causing  such  excessive  irritability  and  excitement  of 
the  ganglionic  spinal  cells  that  these  cells  respond  overwhelmingly  to 

section  of  the  vagi,  of  course  does  not  disprove  vagi  stimulation  by  small  doses  of  the 
drug.  It  is  entirely  possible  that  the  strychnine  may  diminish  cardiac  frequency,  partly 
by  vagi  stimulation,  partly  in  another  way. 

*  Denied,  however,  by  M.  C.  Delezenne,27  who  states  that  in  curarized  animals  the 
exhibition  of  strychnine  is  always  followed  by  an  abatement  of  the  central  temperature, 
which  is  often  but  not  always  accompanied  by  an  increase  in  the  temperature  of  the  sur- 
face, which  increase  he  explains  by  the  supposition  that  the  drug  has  the  power  of  dilating 
the  peripheral  vessels. 


220  GENERAL  REMEDIES. 

the  slightest  stimuli ;  they  also  lower  the  functional  activity  of  the 
motor  nerve-trunks  by  producing  exhaustion  and  by  a  direct  paralytic 
influence.  Death  occurring  during  a  convulsion  is  due  to  cramp  as- 
phyxia, and  is  usually  immediately  preceded  by  loss  of  consciousness ; 
death  between  the  convulsions  is  the  result  of  a  paralytic  asphyxia, 
produced  in  part  by  an  exhaustion,  and  perhaps  also  a  direct  or  second- 
ary paralysis,  of  the  respiratory  centres,  and  in  part  by  a  loss  of  func- 
tional power  of  the  respiratory  nerve-trunks ;  upon  the  cerebrum  and 
upon  the  sensory  nerves  the  alkaloid  exerts  no  demonstrable  influence, 
unless  it  be  that  it  stimulates  feebly  the  special  sense  centres.  There 
is  also  reason  for  believing  that  the  toxic  dose  paralyzes  the  peripheral 
pneumogastric  nerve  and  greatly  depresses  the  heart  itself  and  the 
vaso-motor  system.  The  ozonizing  power  of  the  red  blood-corpuscles 
appears  to  be  lessened  by  toxic  doses  of  strychnine.  The  absorption 
and  the  elimination  of  strychnine  are  rapid,  the  alkaloid  escaping  partly 
in  the  form  of  strychnic  acid  and  partly  unchanged. 

THERAPEUTICS. — Clinical  experience  shows  that  strychnine  is  a  pow- 
erful bitter,  tonic,  and  stomachic,  stimulating  digestion  and  increasing 
the  appetite,  a  conclusion  which  has  been  elaborately  confirmed  by  S.  F. 
Hamper,30  who,  using  Ewald's  test-breakfast,  found  that  the  drug  in- 
creases the  volume  and  digestive  power  of  the  gastric  juice  as  well  as  the 
movements  of  the  stomach.  Strychnine  is,  however,  more  than  a  mere 
stomachic  :  it  is  a  most  useful  tonic  when  there  are  general  relaxation  and 
loss  of  nerve-power.  A  portion  of  its  value  probably  arises  from  ks 
action  upon  the  spinal  motor  nerve-centres  ;  but  in  all  likelihood  it  in- 
fluences other  portions  of  the  cord,  affecting  the  vaso-motor  centres,  and 
most  probably  also  the  trophic  centres.  Be  these  things  as  they  may, 
strychnine  is  the  best  of  all  tonics  in  general  functional  atony  and  relax- 
ation. 

Many  years  ago  Trousseau  taught  that  in  certain  cases  of  chorea 
minor  the  strychnine  preparations  are  very  valuable,  and  Morris  Bene- 
dict 31  asserts  that  the  remedy  is  useful  against  choreic  movements.  It  is 
not  probable  that  in  such  cases  strychnine  exerts  any  specific  influence. 
H.  C.  Wood  has  experimentally  proved  that  in  choreic  dogs  it  greatly 
increases  the  activity  of  the  movements  ;  and  any  good  which  it  may 
achieve  in  chorea  minor  is  probably  due  to  its  tonic  powers. 

The  great  influence  of  strychnine  upon  the  function  of  voluntary 
motion  early  led  to  its  use  in  cases  of  paralysis,  often  with  the  result  of 
doing  harm  rather  than  good.  It  is  very  evident  that  it  can  be  useful 
only  when  the  paralysis  is  dependent  upon,  or  at  least  accompanied  by, 
a  depressed  state  of  the  spinal  motor  centres.  Whenever  there  is  inflam- 
mation or  irritation  of  these  latter,  strychnine  may  do  great  injury  by  in- 
creasing such  irritation,  and  must  never  be  employed.  Like  galvanism, 
in  hemiplegia  it  can  do  only  a  very  limited  amount  of  good,  and  should 
not  be  exhibited  until  irritation  from  the  clot  has  ceased.  It  is  probably 
useful  in  many  forms  of  lead  paralysis,  but  when  the  symptoms  resemble 
those  of  poliomyelitis — i.e. ,  when  there  is  a  multiple  paralysis  with  rapid 
wasting  of  the  affected  muscles  and  alterations  of  the  electro-contractility 


EXCITO-MOTORS.  221 

— we  have  found  strychnine  pushed  to  the  verge  of  poisoning  extraordi- 
narily efficacious. 

The  value  of  strychnine  in  amaurosis  was  first  asserted  by  Nagel.32  In 
atrophy  of  the  essential  nerve-structure  experience  has  shown,  however, 
that  little  is  to  be  expected  from  it  or  any  other  remedy.  To  be  of  use 
the  drug  must,  therefore,  be  used  before  the  stage  of  atrophy  has  been 
reached.  It  is  most  useful  when  employed  in  cases  of  subsiding  neuritis, 
when  atrophy  is  imminent,  as  indicated  by  the  increasing  impairment  of 
vision  and  the  contraction  of  the  fields  for  form  and  color.  Its  value  in 
the  toxic  amblyopias  is  undisputed,  especially  where  the  toxic  agent  is 
tobacco  or  alcohol.  The  distressing  headache  so  frequently  present  during 
the  progressing  atrophy  of  the  optic  nerves  is  often  signally  relieved  by 
steadily  increasing  doses  of  strychnine  or  nux  vomica,  even  although  the 
advancing  loss  of  vision  is  not  arrested.  The  prompt  action  of  the  drug, 
secured  by  daily  or  twice  daily  hypodermic  injections  in  the  temple,  seems 
to  offer  better  results  than  other  methods  of  administration.  The  physio- 
logic impression  should  be  maintained  by  steadily  ascending  doses.  Com- 
mencing with  one-thirtieth  of  a  grain,  the  dose  can,  within  a  few  weeks,  be 
increased  to  one-tenth  or  more,  the  dosage  being  controlled  only  by  the 
tolerance  of  the  patient,  which  varies  greatly,  a  slight  dryness  or  sense  of 
constriction  in  the  throat  or  twitching  of  the  calves  following  the  injection 
being  the  indications  as  to  dosage.  The  acuity  of  vision  and  a  widening 
of  the  fields  may  often  be  noted  within  an  hour  after  the  injection,  which, 
however,  subside  to  former  conditions  as  the  influence  of  the  drug  dis- 
appears. It  must  be  said,  however,  that  in  most  cases  of  serious  optic 
neuritis  the  stage  of  atrophy  is  reached  and  progresses  in  spite  of  all 
known  medical  measures,  but  in  some  cases  strychnine  seems  to  maintain 
the  nutrition  of  the  parts  involved  until  the  stage  of  shrinking  is  at  an  end, 
and  thus  aids  in  preserving  permanently  some  increment  of  vision. 

Strychnine  in  ascending  doses  is  often  of  signal  benefit  in  restoring  the 
proper  binocular  balance  in  cases  of  insufficiency  of  the  ocular  muscles  in 
debilitated  patients, — e.g. ,  after  attacks  of  influenza.  The  strychnine 
should  be  given  hypodermically  in  full  and  ascending  doses  sufficient  to 
produce  and  maintain  a  distinct  physiological  effect.  A  widening  of  the 
field  of  vision  and  improved  central  acuity  may  often  be  noted  after  the 
injection,  which,  however,  subsides  as  the  physiological  impression  dis- 
appears. 

For  a  discussion  of  the  value  of  strychnine  as  a  respiratory  stimulant, 
see  Respiratory  Stimulants,  page  268.  The  alkaloid  is  extremely  valu- 
able in  acute  or  chronic  diseases  of  the  lungs  whenever  the  respiratory 
function  is  failing.  In  long-standing  bronchitis  or  winter  cough,  and  in 
other  obstinate  pulmonic  diseases  with  dilated  right  heart,  the  combina- 
tion of  strychnine  and  digitalis  yields  most  excellent  results.  Much 
advantage  may  often  be  derived,  especially  in  feeble  subjects,  by  adding 
strychnine  to  ordinary  cough  mixture. 

The  value  of  strychnine  in  the  treatment  of  the  respiratory  accidents 


222  GENERAL  REMEDIES. 

of  anaesthesia,  which  was  first  pointed  out  in  the  address  of  H.  C.  Wood 
before  the  Berlin  Congress  in  1890,  is  now  universally  acknowledged. 
The  drug  has  no  less  value  in  other  similar  acute  respiratory  poisonings. 
Very  frequently  the  best  results  are  obtainable  by  using  it  in  combina- 
tion with  other  respiratory  stimulants. 

In  dyspepsia  or  constipation  or  diarrhoea,  connected  with  atony  of  the 
visceral  muscular  coat,  strychnine  is  a  very  valuable  remedy.  In  various 
local  paralyses,  such  as  prolapse  of  the  rectum,  atonic  retention  of  urine, 
atonic  incontinence,  and  loss  of  voluntary  motion  in  certain  groups  of  mus- 
cles from  pressure  upon  or  temporary  injury  of  the  supplying  nerve,  it 
may  be  very  useful.  There  is  reason  to  believe  that  it  sometimes  does 
good  in  these  cases  by  influencing  the  nutrition  of  the  affected  muscle  or 
the  peripheral  nerves  ;  it  should  be  injected  into  the  affected  part. 

Strychnine  is  also  a  serviceable  remedy  as  a  stimulant  in  cases  of 
mental  and  physical  depression  due  to  prolonged  excitement  and  over- 
work. J.  H.  Musser S3  asserts  that  during  the  strain  of  student-life  before 
examinations  it  is  especially  valuable  in  preventing  the  development  of 
asthenopia. 

Strychnine  is  an  extremely  serviceable  remedy  in  the  treatment  of 
cardiac  diseases  with  weakness  of  muscle.  In  mitral  insufficiency  we  have 
seen  it  prolong  life  for  years  after  the  failure  of  digitalis,  and  when  before 
its  administration  immediate  death  seemed  inevitable.  It  should  always 
be  tried  in  cases  of  failing  heart  where  digitalis  disagrees,  it  not  being 
possible  at  present  to  pick  out  those  cases  in  which  brilliant  results  are  to 
be  achieved  by  it.  To  be  effective  it  must  be  given  in  rapidly  ascending 
doses,  the  patient  being  kept,  if  necessary,  for  weeks  and  months  on  the 
verge  of  strychnine-poisoning,  with  distinctly  heightened  reflexes  and 
some  muscular  stiffness.  Clinical  experience  shows  that  it  has  no  cumu- 
lative action,  but  that  the  patient  becomes  accustomed  to  its  use,  so 
that  a  grain  a  day  may  finally  be  given  without  any  serious  effects. 
In  acute  narcotic  poisoning,  in  serious  respiratory  diseases,  in  chronic 
alcoholism,  and  in  plumbic  poliomyelitis,  whenever  strychnine  is  used  for 
a  very  decided  immediate  effect  much  larger  doses  should  be  employed 
than  have  been  heretofore  used.  These  doses  should  be  given  hypo- 
dermically  at  intervals  of  from  four  to  six  hours,  under  the  immediate 
care  of  a  trained  nurse  or  other  equally  skilful  person,  who  should  vary 
the  dose  according  to  the  effect  produced.  In  chronic  neurasthenia  ex- 
cellent results  are  sometimes  obtained  by  slowly  ascending  doses  carried 
over  a  period  of  one  or  two  years. 

TOXICOLOGY. — Sufficient  has  already  been  said  in  regard  to  the  gen- 
eral symptoms  of  stiychnine-poisoning.  It  only  remains  to  discuss  the 
diagnosis.  *  This  is  especially  important,  because  strychnine  is  frequently 


*  A  lesion  found  in  one  case  by  Moriz  Rosenthal  may  possibly  be  characteristic.  It 
consists  of  numerous  small  cross-rents  in  the  heart-muscle,  accompanied  by  small  ex- 
travasations (Nen'enkrankheiten,  1870,  334). 


EXCITO-MOTORS. 


223 


used  criminally,  and  because  not  rarely  it  is  impossible  for  the  chemist  to 
detect  it  after  death. 

The  only  disease  with  which  a  typical  case  of  strychnine-poisoning 
seems  to  be  readily  confounded  is  tetanus,  in  its  various  forms  of  idio- 
pathic,  traumatic,  infantile,  and  hysterical.  Cases  of  strychnine-poison- 
ing have,  however,  occurred  in  which  the  symptoms  have  appeared  to 
point  towards  some  cerebral  disease  or  cerebral  poisoning.  Thus,  in  the 
case  reported  by  Henry  Pilkington,34  the  patient  was  found  unconscious, 
surrounded  by  vomited  matters,  with  excessively  uneven  pupils  and  an 
elevated  temperature.  After  death  both  lateral  ventricles  were  found  to 
contain  clots,  and  there  can  be  little  doubt  that  the  high  arterial  press- 
ure during  an  early  convulsion  had  produced  an  apoplexy  which  was  the 
cause  of  the  subsequent  symptoms  and  death.  It  has  been  asserted 
that  in  fatal  cases  the  duration  of  the  attack  will  always  distinguish  be- 
tween natural  tetanus  and  that  produced  by  poison.  Louis  Starr,55  how- 
ever, reports  traumatic  tetanus  fatal  in  twelve  hours  after  the  first  muscular 
twitchings,  and  within  one  hour  and  a  half  after  the  first  convulsion  ;  and 
death  from  tetanus  has  occurred  fifteen  minutes  after  the  reception  of 
the  injury  (Jaccoud36). 

The  following  table  shows,  we  think,  in  as  clear  and  brief  a  manner  as 
possible  the  differences  between  traumatic  or  idiopathic  tetanus  (No.  i), 
hysterical  tetanus  (No.  2),*  and  strychnic  poisoning  (No.  3).  The  refer- 
ences in  column  No.  3  are  to  authorities  who  affirm  that  the  symptoms 
there  given  are  peculiar  to  poisoning  : 


No.  i. 


Muscular  symptoms  usually 
commence  with  pain  and  stiff- 
ness of  the  back  of  the  neck, 
sometimes  with  slight  muscular 
twitchings  ;  come  on  gradually. 

Jaw  one  of  the  earliest  parts 
affected ;  rigidly  and  persist- 
ently set. 


No.  2. 

Commenced    with    blindness 
and  weakness. 


Muscular  symptoms  com- 
menced with  rigidity  of  the 
neck,  which  gradually  "  crept 
over  the  body,"  affecting  the 
extremities  last. 

Jaw  rigidly  set  before  a  con- 
vulsion, and  remained  so  be- 
tween the  paroxysms. 


No.  3. 

Begins  with  exhilaration  and 
restlessness,  the  special  senses 
being  usually  much  sharpened  .f 
Dimness  of  vision  may  in  some 
cases  be  manifested  later,  after 
the  development  of  other  symp- 
toms ;  but  even  then  it  is  rare. 

Muscular  symptoms  develop 
very  rapidly,  commencing  in 
the  extremities,  or  the  convul- 
sion, when  the  dose  is  large, 
seizes  the  whole  body  simul- 
taneously.! 

Jaw  the  last  part  of  the  body 
to  be  affected  :  its  muscles  relax 
first,  and,  even  when  during  a 
severe  convulsion  it  is  set,  it 
drops  as  soon  as  the  latter 
ceases,  jj 


*  Column  No.  2  is  from  an  actual  case.  See  trial  of  Mrs.  VVharton,  New  York  Medi- 
cal Record,  1873. 

t  Taylor,  On  Poisons,  683 ;  Wormley,  Micro- Chemistry  of  Poisons,  536. 

t  Wormley,  536;  Still€,  Therapeutics,  ii.  148. 

\  Taylor,  On  Poisons,  134,  682  ;  Wormley,  536,  540,  541 ;  Tardieu,  Sur  V  Empoisonne- 
ment,  924. 


224 


GENERAL  REMEDIES. 


No.  i. 

Persistent  muscular  rigidity, 
very  generally  with  a  greater 
or  less  degree  of  permanent 
opisthotonos,  emprosthotonos, 
pleurothotonos,  or  orthotonos. 


Consciousness  preserved  un- 
til near  death,  as  in  strychnic 
poisoning. 


Draughts,  loud  noises,  etc., 
produce  convulsions,  as  in 
strychnic  poisoning. 

May  complain  bitterly  of 
pain. 


Eyes  open,  rigidly  fixed,  dur- 
ing the  convulsion. 


No.  2. 

Persistent  opisthotonos,  and 
intense  rigidity  between  the 
convulsions ;  and  after  the  con- 
vulsions had  ceased  the  opis- 
thotonos and  intense  rigidity 
lasted  for  hours. 


Consciousness  lost  as  the  sec- 
ond convulsion  came  on,  and 
lost  with  every  other  convul- 
sion, the  disturbance  of  con- 
sciousness and  motility  being 
simultaneous. 


Desired  to  be  fanned. 


Crying-spells,  in  which  he 
"  sobbed  violently,"  and  "  cried 
like  a  child,"  alternated  with 
the  convulsions. 

Eyes  closed. 

The  spasms  in  the  leg  must 
have  been  partial,  as  the  feet 
were  crossed  and  toes  inverted, 
which  could  not  happen  if  all 
the  muscles  were  involved,  be- 
cause the  muscles  of  eversion, 
being  very  much  the  stronger, 
would  of  necessity  overcome 
the  antagonistic  muscles,  and 
the  feet  be  everted. 


No.  3. 

Muscular  relaxation  (rarely  a 
slight  rigidity)  between  the  con- 
vulsions, the  patient  being  ex- 
hausted and  sweating.  If  re- 
covery occur,  the  convulsions 
gradually  cease,  leaving  merely 
muscular  soreness,  and  some- 
times stiffness  like  that  felt  after 
violent  exercise.* 

Consciousness  always  pre- 
served during  convulsions,  ex- 
cept when  the  latter  become  so 
intense  that  death  is  imminent 
from  suffocation,  in  which  case 
sometimes  the  patient  becomes 
insensible  from  asphyxia,! 
which  comes  on  during  the  lat- 
ter part  of  a  convulsion,  and  is 
almost  a  certain  precursor  of 
death. 

The  slightest "  breath  of  air" 
produces  a  convulsion. J: 

Patient  may  scream  with  pain, 
or  may  express  great  appre- 
hensions, but  "  crying-spells" 
would  appear  to  be  impossible. 

Eyes  stretched  wide  open.fi 

Legs  stiffly  extended,  with 
feet  everted, ||  as  the  spasms 
affect  all  the  muscles  of  the  leg. 


Death  from  strychnine  in  man  and  other  mammals  mostly  occurs  in 
a  convulsion,  and  under  these  circumstances  is  undoubtedly  due  to  as- 
phyxia, caused  by  the  unyielding,  spasmodically  contracted  muscles.  In 
man,  death  sometimes  occurs  not  in  a  paroxysm,  but  during  relaxation, 
and  probably  then  is  the  result  not  only  of  the  exhaustion  following  effort, 
but  also  of  the  direct  action  of  the  poison  upon  the  respiratory  centre 
and  nerves. 

In  frogs,  death  must  occur  from  other  causes,  since  a  frog,  as  shown  by  Claude 
Bernard,  will  live  for  days  after  removal  of  its  lungs,  probably  by  breathing  through 
its  skin.  The  causes  of  death  in  the  frog  are  not  hard  to  find  when  the  physiological 
action  of  the  drug  is  known.  The  lymph  and  true  hearts  (Kolliker,  Harley37)  are 
very  much  affected,  but  the  chief  factor  is  no  doubt  paralysis  of  the  motor  nerves. 

*  Taylor,  On  Poisons,  134,  136,  682 ;  Wormley,  536,  540,  541  ;  Tardieu,  924,  938,  939 ; 
Husemann,  Handbuch  der  Toxicologie,  168. 

t  Wormley  (ist  ed.),  536;  Taylor,  Medical  Jurisprudence,  331,  332;  Wharton  and 
Stille,  Medical  Jurisprudence,  paragraph  757 ;  Tardieu,  923 ;  Stille,  Therapeutics,  148. 
J  Stille,  Therapeutics,  148. 

#  Ibid.  ;  Wormley,  536 ;  Tardieu,  924. 

||  Tardieu,  924 ;  also  other  authorities,  which  we  have  neglected  to  note,  and  at  present 
writing  have  not  at  hand. 


EXCITO-MOTORS.  225 

Honigmann S8  reports  a  remarkable  case,  in  which  acute  inflammation 
of  the  kidneys  followed  strychnine-poisoning. 

The  minimum  fatal  dose  of  strychnine  is  probably  something  under 
half  a  grain  ;  the  latter  quantity  has  several  times  caused  death,  once 
in  a  man  in  twenty  minutes  ; 39  one- third  of  a  grain  given  at  intervals  in 
fractional  doses  has  produced  such  alarming  symptoms  as  to  indicate  that 
in  a  single  dose  it  might  readily  destroy  life  ;  one-hundredth  of  a  grain 
is  said  to  have  killed  a  child  three  and  a  half  months  old  ; *°  but  ten  grains 
(Tschepke41),  twenty  grains  (A.  E.  Connor"),  also  twenty-two  grains 
(George  Gray43) — taken  on  a  full  stomach  and  retained  two  hours — have 
failed  to  cause  death,  in  each  case  probably  on  account  of  slow  absorption.* 

The  question  as  to  the  possibility  of  acquiring  immunity  to  strychnine 
has  become  an  important  one  in  certain  cases  of  alleged  murder,  and  also 
has  some  bearing  upon  the  practical  use  of  the  drug.  Clinical  experience 
undoubtedly  favors  the  view  that  strychnine  may  be  given  continuously 
for  months  or  years  without  any  distinct  immunity,  and  H.  A.  Hare48  has 
been  unable  to  produce  in  rabbits  by  ascending  doses  any  distinct  lessen- 
ing of  susceptibility  to  the  poison. 

In  treating  poisoning  by  strychnine,  a  chemical  antidote  should  be  at 
once  administered,  such  as  tannic  acid  or  iodine  or  one  of  its  soluble  salts. 
As,  however,  the  compounds  formed  in  the  stomach  by  these  substances 
are  not  permanent,  theoretically  a  quick  emetic  may  sometimes  be  ad- 
visable. Potassium  permanganate  has  the  power  of  oxidizing  strychnine, 
but  its  value  as  a  practical  antidote  has  not  as  yet  been  determined.  For 
the  lessening  of  the  excitability  of  the  spinal  cord  various  spinal  depress- 
ants have  been  from  time  to  time  recommended.  No  spinal  depressant, 
however,  which,  like  aconite  or  tobacco,  is  also  powerfully  depressant  to 
the  circulation,  should  be  used.  The  remedies  which  may  be  employed 
are  potassium  bromide,  chloral, f  chloroform,  and  amyl  nitrite.  Alcohol 
has  been  strongly  recommended  by  some  authorities  (Amagat,  Stacchini) 
as  antidotal ;  and  when  the  great  muscular  relaxation  of  drunkenness  is 
remembered,  it  seems  very  probable  that  the  commendation  has  some 
basis.  Husemann  has,  however,  shown  that  alcohol  can  scarcely  be 
looked  upon  as  a  real  antagonist  to  the  alkaloid. 

The  best  treatment  of  strychnine-poisoning  is  apparently  to  be  found 
in  the  conjoint  use  of  chloral  and  potassium  bromide,  with,  when  convul- 
sions are  very  threatening,  inhalations  of  amyl  nitrite  or  chloroform. 
Half  an  ounce  of  the  bromide  with  half  a  drachm  to  a  drachm  of  chloral 

*  In  a  preliminary  investigation,  William  Salant  (Amer.  Med.,  Aug.  1902)  failed  to 
detect  small  quantities  of  strychnine  which  had  been  previously  added  to  the  contents  of 
the  large  intestine  of  normal  rabbits.  Subsequently  (Amer.  Med.,  June,  1903),  however, 
he  proved  that  these  strychnized  contents  were  actively  poisonous,  and  that  therefore  the 
failure  to  detect  strychnine  lay  at  the  door  of  the  chemical  methods  employed,  and  sug- 
gested a  new  method  of  looking  for  the  alkaloid.  The  chief  importance  of  this  investi- 
gation is  the  side-light  which  it  throws  upon  failures  of  chemists  in  cases  of  poisoning. 

t  For  detailed  discussion  of  the  relations  of  strychnine  and  chloral,  with  account  of 
experiments  by  various  investigators,  see  tenth  edition  of  the  present  treatise. 

15 


226  GENERAL  REMEDIES. 

may  be  given  at  once  in  a  severe  case  ;  and,  if  necessary,  every  twenty 
minutes  afterwards  two  drachms  of  the  first  and  fifteen  grains  of  the 
second  remedy  may  be  exhibited. 

Chloroform  or  amyl  nitrite  should  be  given  by  inhalation  whenever 
the  convulsions  are  extremely  severe,  and  if  the  patient  cannot  swallow, 
a  drachm  of  chloral  may  be  injected  into  the  rectum,  or,  especially 
where  respiration  is  very  seriously  affected,  five  minims  of  amyl  nitrite 
may  be  given  hypodermically.  It  is  essential  to  remember  that  any 
disturbance  of  the  patient  may,  when  the  symptoms  are  well  developed, 
bring  about  a  fatal  convulsion.  Thus,  we  have  seen  death  occur  in 
a  convulsion  caused  by  an  effort  to  get  the  mouth  open  to  give  a  remedy. 
Hence,  unless  the  case  is  seen  in  the  beginning,  no  attempt  should  be 
made  to  evacuate  the  stomach.  Artificial  respiration,  which  has  been 
highly  commended  by  some,  cannot,  we  believe,  ever  be  of  service  in 
human  poisoning. 

Leube  was,  we  believe,  the  first  to  demonstrate  that  forced  artificial  respira- 
tion in  animals  will  not  only  very  greatly  lessen  the  production  of  convulsions  by 
strychnine,  but  will  also  affect  the  final  result  of  the  poisoning.  After  considerable 
discussion,  the  accuracy  of  the  results  reached  by  Leube  has  been  finally  estab- 
lished. The  method  in  which  the  forced  respiration  acts  is  at  present  unknown.  It 
has  been  shown  by  W.  J.  Gies  and  S.  J.  Meltzer46  that  whilst  artificial  respiration 
completely  suppresses  the  reflex  irritability  due  to  strychnine-poisoning,  it  does  not 
distinctly  affect  the  increased  reflex  irritability  induced  by  section  of  the  spinal  cord  : 
that  the  influence  of  the  artificial  respiration  is  not  the  result  of  any  superoxidation 
of  the  blood  seems  to  be  proven  by  the  fact  discovered  by  Gies  and  Meltzer,  that 
insufflation  of  the  lungs  of  the  animal  with  pure  hydrogen  gas  has  the  same  effect  as 
artificial  respiration.  None  of  the  ordinary  methods  of  artificial  respiration  in  man 
is  sufficiently  powerful  to  be  of  any  value,  whilst  the  manipulations  of  the  physician 
would  certainly  tend  to  increase  the  strychnic  spasm.  The  curious  discovery  of 
Leube  is  therefore  of  scientific  rather  than  of  practical  value.* 

ADMINISTRATION. — As  a  tonic,  strychnine  sulphate  may  be  given  in 
granule  in  doses  of  from  one-fortieth  to  one-twentieth  of  a  grain  (0.0016- 
0.0032  Gm. ).  Whenever  it  is  desired  to  push  the  remedy  to  its  physiologi- 
cal limit,  it  should  be  given  hypodermically  in  ascending  doses  until  restless- 
ness, general  excitement,  muscular  twitching,  stiffness  of  the  neck  or  legs,  or 
other  symptoms  are  manifested.  In  many  cases  of  palsies,  especially  with 
trophicchanges  in  the  muscles,  the  best  effect  seems  to  be  obtained  by  inject- 
ing the  strychnine  salt  directly  into  the  affected  muscle.  If  proper  antiseptic 
precaution  be  taken,  hypodermic  injections  do  not  cause  local  irritation. 


*  Gies  and  Meltzer  found  that  the  animal  under  strychnine  could  be  kept  alive  by 
insufflation  of  pure  hydrogen  for  thirty  minutes,  without  manifesting  any  signs  of 
asphyxia,  dyspnoea,  or  cyanosis.  This  is  so  absolutely  destructive  of  the  foundations  of 
modern  physiology  that  it  is  impossible  to  avoid  believing  there  was  some  mistake  or 
fallacy  in  the  experimental  technic.  The  literature  of  this  subject  is  so  thoroughly  given 
in  the  paper  of  Gies  and  Meltzer  that  we  content  ourselves  with  adding  Jochelsohn 
(Rossbach's  Untersuchungen,  \.  92). 


EXCITO-MOTORS.  227 

BRUCINE. — Strychnine  clings  so  closely  to  brucine  that  the  physio- 
logical actions  attributed  to  brucine  may  be  in  truth  caused  by  contami- 
nating strychnine.  L.  Wintzenreid l  found  that  brucine  acts  as  a  stimu- 
lant to  the  spinal  cord  and  a  paralyzant  to  the  motor  nerves,  but  does  not 
influence  the  cerebrum  or  the  sensory  nerves  ;  and  that  in  the  higher  ani- 
mals, at  first  it  increases  the  arterial  pressure  and  afterwards  lessens  it, 
in  large  doses  paralyzes  the  vagi,  causes  death  by  asphyxia,  and  in  other 
ways  acts  like  strychnine.  The  more  recent  experiments  of  Lauder 
Brunton 2  are  in  accord  with  the  results  obtained  by  Wintzenreid  in  show- 
ing that  brucine  causes  spinal  convulsions  in  mammals  when  injected  di- 
rectly into  the  circulation.  Brunton  found,  however,  that  when  taken  by 
the  mouth  it  produces  no  symptoms,  probably  because  it  is  excreted  as 
rapidly  as  it  is  absorbed.  In  an  elaborate  study,  Edward  T.  Reichert* 
reached  the  conclusion  that  the  physiological  action  of  brucine  is  pre- 
cisely that  of  strychnine,  except  that  brucine  is  much  less  rapidly 
absorbed,  is  from  forty  to  fifty  times  less  powerful  as  a  convulsant,  is  more 
poisonous  to  the  sensory  nerves,  and  is  more  uncertain  in  its  effect  upon 
bodily  temperature.  Further,  brucine  appears  to  have  an  action  upon 
the  volitional  centres  of  the  frog  different  from  that  of  strychnine,  pro- 
ducing a  brief  period  of  motor  paralysis  preceding  the  stage  of  spinal 
convulsion  (Mays,  Reichert).*  Thomas  I.  Mays*  found  that  brucine 
locally  applied  to  the  nerves  of  the  frog  rapidly  produces  a  paralysis  of 
the  sensory  fibres.  This  led  him  to  test  it  as  a  local  anaesthetic  in  man, 
and  he  asserts  that  a  five  or  ten  per  cent,  solution  applied  to  the  mucous 
membrane  of  the  mouth  caused  rapid  loss  of  sensibility  ;  also  that  a 
twenty  per  cent,  solution  applied  to  the  back  of  the  hand  caused  pro- 
nounced impairment  of  sensibility.  Mays  used  this  solution  with  excel- 
lent results  for  the  relief  of  the  itching  of  chronic  pruritus.  Ralph  W. 
Seiss 5  and  Charles  H.  Burnett  have  found  that  the  application  of  a  five 
per  cent,  solution  in  the  local  pruritus  of  inflammation  in  or  about  the 
external  ear  usually  gives  very  marked  relief.  Burnett  states  that  his 
results  were  far  more  satisfactory  than  those  which  he  has  obtained  with 
cocaine.  In  using  brucine  as  a  local  anaesthetic  it  is  essential  that  it 
be  chemically  pure  :  the  nitrate  or  the  sulphate  may  be  selected,  and  one 
drop  of  hydrochloric  or  sulphuric  acid  should  be  added  to  the  solution 
for  each  three  grains  of  the  alkaloid  salt. 


REFERENCES. 

STRYCHNINE.  5.  RAUTENFELD    .   .  In.  Dis.,  Dorpat,  1884. 

1.  BOULEY   and    COLIN     .  Trait6    de    Physiol.         6-  WORMLEY  ....  Micro-Chemistry,  2d  ed. 

comparte,  ii.  91.  7-  KRATTKR    .   .   .   .  W.  M.  W.,  1882. 

2.  MELTZER    ....  J.  Ex.  M.,  i. ;   A.  J.  M.  S.,         8-  PLUGGE Arch.  d.  Pharm.,  1883. 

Nov.  1899.  9-  BORZI A.  I.  B.,  1899. 

3.  LOVETT J.  P.,  ix.  I0-  LEUBE A.  A.  P.,  1867,  630. 

4.  LESSER Vierteljahrschr.  f.  gericht.        "•  DEMME Syd.  Soc.  Year-Book,  1865- 

Med.,i898,  xv.27and26i.  '66,441. 

*  For  a  research  showing  the  comparative  action  of  strychnine  and  brucine  on  differ- 
ent species  of  frogs,  see  Sautesson  (Archivf.  Exper.  Path.  u.  Pharm.,  xxxv.). 


228 


GENERAL  REMEDIES. 


12.  BERNARD  .  .  . 
13.  VAN  DEEN  .  .  . 

14.  BlERNACK!  .  . 
15.  KOLLIKER  .  .  . 

REFERENCE 

.  Lemons  sur  les  Substances 
Toxiques. 
.  Physiol.  de  la  Moelle  6pi- 
niere,  1860,  iii.  130. 
.  Th.  M.,  xii. 
.  V.  A.  P.  A.,  x. 

IS.—  Continued. 

33.  MITSSER  .  .  . 

.   .  T.  G.,  ii.  10. 

34.   PlLKlNGTON    . 

35.  STARR  .... 

.   .  L.  L.,  1893,  i. 
P.  M.  T  ,  iii.  311 

36.  JACCOUD  .  .  . 
37.  HARLEY  .  .   . 

.   .  Path.  Intern.,  i.  441. 
.  .  L.  L.,  July  1856. 

38.   HONICMANN  . 
39- 

40. 
41.  TSCHEPKE  .  . 
42.  CONNOR  .  .  . 
43.  GRAY    .... 

.   .  S.  Jb.,  ccxxiii.  21. 
Guy's     H.     R.,     1865,    xi. 
208. 
P.  J.  and'Tr.,  viii.  1010. 
.  .  D.  K.  C.,  1861. 
.   .  O.  M.  R.,  1879,  12. 
.   .  B.  M.  J.,  1880,  i.  477. 

16.  POULSON  .  .  . 
17.  SAUTESSON  .  . 
18  MAYER  .  . 

.  A.  E.  P.  P.,  xxvi. 
A  E  P  P  ,  1894,  xxxv. 

Med  Jahrb  d  k  k  Geseli- 

19.  KLAPP  . 

schaft  d.  Aerzte  zu  Wien, 
1872,  112. 
J.  N.  M.  D.,  Oct.  1878. 

20.  REICHERT  .  .  . 
21.  LAHOUSSE  .  .  . 

22.  KlONKA  .  .  .  . 

.  T.  G.,  April,  1892. 
.  C.  R.  S.  B.,  xci. 
.  A.  P.  I.,  1898,  v.  in. 

44.  FALCK  .... 

.  Cb.  M.  W..  1800.  XT. 

45.  DERBY  B.  M.  and  S.J.,  1902,  cxlvi. 
508. 
46.  GIES   and    MELTZBR  .  J.   Ex.   M.,  1902,  vi. 
107. 
47.  CARRARA    ....  Cb.  Inner.  Med.,  1901. 
48.  HARK   A.  T.  P..  IOOT.  v. 

23.  MAURKL 

.  B.  G.  T.,  March,  1892. 

24.  WOOD  

.  J.  P.,  1892. 

25.  OEEKMEIER  .  . 
26.  Mosso  

.  In.  Dis.,  Erladgen,  1891. 
A.  I.  B.,  1886. 

27.  DELEZBNNK  .  . 
28.  VON  HIPPEL  .  . 

29.  COHN  
30.  HAMPER  .  . 

.  Bull.  Med.  du.  Nord,  1895, 
xxxiv. 
.  Wirkung   des    Strychnins 
auf     die    normale    und 
kranke    Augen,    Berlin, 
1873- 
.  W.  M.  W.,  1873,  No.  42. 
L.  M   R  ,  Feb  1891 

49.  HARNACK  .   . 

.  A.  E.  P.  P..  IOOT.  xlix. 

50.  MKLTZBR  and  LANGMANN  .  J.  M.  R.,   1903, 
ix. 

BRUCINE. 

i.  WINTZENREID  .   .  In.  Dis.,  Geneva,  1882. 
2.  BRUNTON    .  .   .  .  J.  Chem.  S.,  188. 
3.  REICHERT  .  .  .  .  M.  News,  April,  1893. 
4.  MAYS    T.  P..  viii. 

31.  BENEDICT  .  .  . 
32.  NACEL  .  .  .  . 

.  W.  M.  W.,  1891,  xli. 
.  Die  Behandlung  der  Am- 

T    C"             '"    Acn 

aurosen  u.  Amblyopeen 
mil     Strychnin,    Tubin- 
gen, 1871. 

FAMILY   VI.— DEPRESSO-MOTORS. 


UNDER  this  heading  are  considered  certain  drugs  which  are  used  for 
the  purpose  of  lessening  the  activity  of  the  spinal  cord.  They  have, 
except  in  this  particular,  but  little  in  common  in  their  action,  and  must 
be  studied  individually. 

PHYSOSTIGMA— CALABAR    BEAN.     U.S. 

An  irregular,  kidney-shaped  bean,  about  an  inch  in  length  and  three- 
fourths  of  an  inch  wide,  the  product  of  the  Physostigma  venenosum,  a 
perennial  woody  creeper  of  Calabar,  Africa,  where  the  bean  has  been 
used  by  the  natives  as  an  ordeal  test  for  criminals,  witches,  etc. ,  since 
time  immemorial.  It  contains  an  alkaloid  known  as  physostigmine,  or 
eserine.  E.  Harnack  and  L.  Witkowski 1  have  described  a  powerful  teta- 
nizing  alkaloid,  calabarine,  which  is  sometimes  abundant  in  commercial 
extracts  of  Calabar  bean.  It  is  probably  a  decomposition  product  from 
that  alkaloid  (see  also  Husemann2).  Isophysostigmine  according  to  Ogiu34 
is  similar  in  its  action  to  physostigmine  but  more  powerful. 

PHYSIOLOGICAL  ACTION. — Local  Action  and  Elimination. — No  ap- 
parent irritant  action  occurs  from  therapeutic  doses  of  Calabar  bean  or  its 
alkaloid. 

Both  absorption  and  elimination  are  very  rapid.  N.  Teich  and  D. 
Schweder 3  have  both  found  physostigmine  in  the  urine  half  an  hour  after 
its  ingestion.  Although  the  alkaloid  has  been  detected  in  various  secre- 
tions by  Dragendorff  and  his  pupil  Pauder,  it  chiefly  escapes  through 
the  kidneys.  Its  effect  upon  the  urinary  secretion  has  never  been 
studied,  excepting  in  that  Merson  *  states  that  it  decreases  the  excretion 
of  urea  and  other  urinary  solids  in  paresis. 

General  Action. — No  sensible  effects  are  perceptible  after  the  full 
therapeutic  dose  of  Calabar  bean,  except  it  be  slight  weakness  and  dis- 
like for  muscular  exertion.  The  symptoms  produced  by  large  doses 
are  giddiness,  lessened  heart-action,  great  muscular  weakness,  with,  in 
most  cases,  contraction  of  the  pupil,  and  sometimes  vomiting,  and  still 
more  commonly  purging,  which  may  be  very  free.  A  pupil  of  Gubler 
took  0.15  grain  of  eserine  sulphate,  and  suffered,  after  a  time,  nausea, 
giddiness,  and  intense  muscular  weakness,  so  that  he  could  not  stand  ; 
three-quarters  of  an  hour  afterwards  he  vomited  some  of  the  solution 
mixed  with  bile,  but  his  strength  did  not  begin  to  return  for  two  and  a 
half  hours. 

When  an  animal  receives  a  small  fatal  dose  of  Calabar  bean,  after  a  time  mus- 
cular tremors  appear,  and  almost  immediately  the  victim  falls  to  the  ground,  or 
lies  down,  in  a  state  of  perfect  muscular  flaccidity.  The  pupils  generally  contract, 

229 


230  GENERAL    REMEDIES. 

and  the  respirations  become  slow,  irregular,  and  often  stertorous.  All  reflex  actions 
are  almost  at  once  diminished,  and  this  diminution  grows  greater  and  greater,  until 
it  ends  in  their  complete  abolition.  So  long  as  the  condition  of  the  motor  system 
allows  of  it,  evidences  of  sensibility  are  manifested  whenever  the  animal  is  in  any 
way  injured.  According  to  dementi  Papi,5  the  voice  is  completely  lost.  The  mus- 
cular tremors  persist  during  the  whole  period  of  paralysis,  and,  indeed,  even  after 
cessation  of  the  respiration.  They  vary  greatly  in  intensity,  and  in  some  cases  are 
so  severe  (Eraser)  as  to  simulate  general  convulsions.  As  the  minutes  go  by,  the 
rhythm  of  the  respiration  becomes  more  and  more  affected,  and  at  last  death  takes 
place  quietly,  consciousness  being  preserved  until  the  last  few  gasping  respirations 
close  the  scene.*  The  pupils  sometimes,  but  not  always,  dilate  immediately  after 
death.  According  to  the  experiments  of  Fraser,  the  bodily  temperature  is  slightly 
elevated. 

After  a  small  lethal  dose  of  the  poison,  the  fatal  result  is  always  due  to  failure 
of  the  respiration,  and  if  the  body  be  at  once  opened  the  heart  is  found  still  beat- 
ing ;  indeed,  it  has  been  seen  to  continue  to  do  so  for  one  and  a  half  hours  after 
death  ( Fraser) .  If  a  very  large  amount  of  the  drug  be  given,  the  animal  falls  almost 
at  once,  paralyzed,  with  only  a  few  muscular  twitchings.  The  pupils  contract,  and  in  a 
very  short  time  the  gasping  respiration  ceases.  The  heart  is  now  found  distended 
and  passive,  but  often  will  contract  under  the  stimulation  of  a  galvanic  current. 

Nervous  System. — Upon  the  cerebrum  physostigmine  has  no  per- 
ceptible influence.  The  paralysis  and  loss  of  reflex  activity  which  it 
produces  are  undoubtedly  due  to  a  depressant  action  upon  the  motor 
cord.  Thus,  Fraser,  Harnack,  Witkowski,  and  others  have  found  that 
if  in  the  frog  a  peripheral  nerve  be  protected  by  tying  its  artery  and  the 
batrachian  be  poisoned  with  Calabar  bean,  the  paralysis  in  the  protected 
limb  occurs  part  passu  with  that  in  the  remainder  of  the  body.  Again, 
Fraser  divided  the  spinal  cord  of  a  frog,  and  then  cut  or  tied  all  the 
blood-vessels  going  to  the  posterior  section  of  it.  After  this,  the  animal 
was  poisoned  with  physostigma,  and  while  the  usual  symptoms  developed 
themselves  in  the  anterior  portion  of  the  body,  reflex  actions  were  unaf- 
fected in  the  posterior  part.  Further,  Fraser 6  has  found  that  when  the 
poison  is  applied  directly  to  the  cord,  fibrillary  contractions,  due  prob- 
ably to  a  local  irritant  influence,  are  induced  in  the  muscles  supplied  from 
below  the  point  of  application,  but  in  a  little  while  all  movements  cease, 
and  even  galvanization  of  the  cord  itself  is  unable  to  elicit  response.  It 
is  asserted  by  several  investigators  that  the  extremely  minute  dose  of 
physostigmine  acts  as  a  stimulant  to  the  spinal  cord.  Although  this  may 
be  true,  it  seems  at  present  writing  improbable,  f 

*  Kohler,  Rossbach,  and  others  have  affirmed  that  Calabar  bean  produces  a  tetanic 
intoxication.  A  plausible  explanation  of  these  singular  observations,  and  of  many  of  the 
discrepancies  of  authorities,  is  to  be  found  in  the  discovery  of  calabarine.  Its  discoverers 
state  that  it  produces  first  a  violent  tetanus,  and  afterwards  paralysis.  It  is  plain  how  its 
presence  in  varying  amounts  in  Calabar  bean  preparations  would  modify  their  action. 
The  researches  of  Kohler,  of  Vintschgau,  and  of  Rossbach  and  Frohlich  are  especially 
open  to  doubt,  on  account  of  their  statements  that  Calabar  bean  tetanizes.  It  is  very 
probable  that  the  extracts  used  by  them  contained  a  notable  percentage  of  calabarine. 

t  Papi  states  that  in  frogs  the  stage  of  exaltation  and  reflex  activity  precedes  the 
stage  of  depression.  M.  Vintschgau  ( Stitzungsb.  Math.  Nat.  Classe  Akad.  Wissen.  Wien., 
1867,  Bd.  lv.,  Abth.  ii.  49)  affirms  that  in  a  frog  whose  iliacs  he  had  tied  the  poison  pro- 
duced violent  convulsions,  which  affected  the  protected  legs,  and  must,  therefore,  have 
been  of  central  origin.  Two  plausible  explanations  of  this  suggest  themselves  :  first, 


DEPRESSO-MOTORS.  231 

Nerves. — Although  there  is  reason  for  believing  that  physostigmine  is 
capable  of  affecting  both  motor  and  sensory  nerve-trunks,  yet  this  action 
is  so  feeble  as  probably  to  take  no  part  in  the  production  of  symptoms. 
The  afferent  nerves  are  less  sensitive  than  the  efferent,  since  Eraser  has 
found,  first,  that  the  local  application  of  a  strong  solution  of  the  poison 
to  a  nerve  kills  the  efferent  or  motor  fibres  before  the  afferent  or  sensory, 
although  the  functions  of  both  of  them  are  finally  abolished  ;  second, 
that  when  the  arteries  in  the  left  leg  of  a  frog  are  tied,  and  the  animal 
poisoned  both  with  Calabar  bean  and  strychnine,  there  comes  a  time 
when  reflex  movements  are  excited  in  the  left  leg  by  irritation  of  the  right 
foot,  although  irritation  of  the  left  foot  does  not  cause  movements  in 
the  right  leg, — i.e.,  the  impulse  is  able  to  travel  up  the  poisoned  nerve 
of  the  right  leg  but  not  down  it. 

The  extreme  feebleness  of  the  influence  of  physostigmine  is  shown  by 
the  fact  that  the  frog's  nerves  are  often  active  after  death  from  Calabar 
bean  (Laschkewich,7  Vintschgau,8  and  Eraser)  ;  and  Eraser  has  deter- 
mined that  after  the  fatal  result  has  been  produced  rapidly  with  physo- 
stigmine, the  rate  of  conduction  of  impulse  is  as  rapid  in  the  nerve  to 
which  the  poison  has  had  free  access  as  in  one  which  has  been  protected 
by  the  tying  of  its  artery. 

Loss  of  power  in  the  motor  nerves  after  poisoning  by  Calabar  bean  has 
been  found  in  the  frog  only,  and,  further,  only  when  the  dose  has  been  so 
small  that  the  heart  has  continued  to  beat  long  after  the  cessation  of  res- 
piration, so  that  the  nerves  had  been,  as  it  were,  macerated  in  a  solution 
of  the  poison.  Harnack  and  Witkowski  deny  that  physostigmine  has  even 
this  feeble  influence  upon  the  nerve-trunks.  The  loss  of  power  is  prob- 
ably in  the  termination  of  the  nerve  rather  than  in  the  trunk,  for  Eraser 
found  that  when  all  the  blood-vessels  supplying  the  gastrocnemius  muscle 
were  cut  in  a  frog  and  the  animal  poisoned,  at  a  certain  time  irritation  of 
the  crural  nerve  produced  spasms  of  the  gastrocnemius  alone. 

Muscles. — The  continuance  of  the  muscular  movements  after  death 
indicates  that  they  are  due  to  a  direct  action  of  the  drug  upon  the  muscles. 
This  conclusion  is  established  by  the  experiments  of  Laschkewich,  of 
Eraser,  and  of  Leven  and  Laborde.9  All  of  these  investigators  have 
noted  that  after  death  these  contractions  are  increased  by  exposure  to  the 
air  and  by  direct  stimulation  of  the  muscles  ;  and  Eraser  has  found  that 
they  occur  in  the  frog  during  life  after  section  of  the  supplying  nerve, 
and  also  in  a  muscle  actually  cut  out  of  the  body.  Laschkewich  has  con- 
firmed the  latter  fact  in  the  case  of  warm-blooded  animals,  and  Leven 
and  Laborde  have  proved  that  previous  destruction  of  the  lower  end  of 

that  the  physostigmine  used  contained  calabarine  or  other  active  impurity  ;  second,  the 
well-known  fact  that  certain  spinal  depressants  produce  convulsions,  or  even  excite  re- 
flex action,  by  paralyzing  reflex  inhibition,  or  in  some  unknown  way.  The  probability  of 
the  impurity  of  the  alkaloid  is  increased  by  the  assertion  of  Harnack  that  Merck's  "  cala- 
barinum  purum"  contains  little  or  no  calabarine.  Schweder,  however,  asserts  that  pure 
physostigmine,  in  small  doses,  acts  as  a  distinct  stimulant  to  the  cerebral,  respiratory,  and 
vaso-motor  centres. 


232  GENERAL   REMEDIES. 

the  spinal  cord  in  a  guinea-pig  does  not  prevent  the  development  of  the 
muscular  twitchings  in  the  hind  legs.  Schweder  contends  that  the  action 
of  the  poison  is  not,  however,  upon  the  muscular  structure  itself,  but 
upon  the  peripheral  nerve-endings  in  the  muscle,  basing  his  conclusions 
especially  upon  the  asserted  fact,  that  previous  hypodermic  injections 
of  atropine  or  curare  prevent  the  development  of  rigidity  in  the  snake 
poisoned  with  physostigmine.  It  is  certain  that  the  final  paralysis  pro- 
duced by  Calabar  bean  is  not  of  muscular  origin,  since  at  the  time  of 
death  the  contractility  of  the  muscles  is  in  no  way  diminished,  but,  on  the 
contrary,  Fraser  has  noted  that  loss  of  contractility  and  rigor  mortis  are 
greatly  delayed  in  Calabar-bean  poisoning. 

Circulation. — In  the  mammal,  after  therapeutic  and  even  toxic  doses, 
the  cardiac  action  of  physostigmine  is  subordinate  to  its  influence  upon 
the  nerve-centres  ;  but,  as  has  been  shown  by  Fraser,  when  overwhelm- 
ing doses  of  the  poison  are  administered,  especially  if  they  be  injected 
into  the  jugular  vein,  death  results  from  syncope,  or  from  consentaneous 
failure  of  the  cardiac  and  the  respiratory  functions,  and  the  heart  is  found 
arrested  in  diastole,  flaccid,  but,  according  to  Fraser  and  to  C.  Arnstein 
and  P.  Sustschinsky,10  responding,  though  feebly  and  uncertainly,  to 
direct  stimulation.  In  the  poisoned  frog  the  early  contractions  of  the 
heart  are  slower  and  more  forcible  than  the  normal  (Harnack  and  Wit- 
kowski)  ;  whilst  the  arrested  heart  is  insensible  to  stimuli  (Rossbach  and 
Frohlich11). 

When  smaller  doses  of  the  poison  are  exhibited,  there  is  slowing  of 
the  heart's  action  (Laschkewich,  Fraser,  and  J.  Tachau12).  Although, 
according  to  the  experiments  of  Fraser,  there  is  at  first  a  slight  fall  of  the 
blood-pressure,  which  is  probably  due,  as  he  believes,  to  diminished 
pulse-frequency,  yet,  in  spite  of  the  continuance  of  the  slow  pulse,  the 
arterial  tension  soon  recovers  itself,  and  remains  for  a  long  time  much 
above  the  normal  point,  while  at  the  same  time  the  individual  cardiac 
beats  are  greatly  increased  in  strength  (Fraser,  Bezold  and  Gotz*). 
Finally,  the  arterial  pressure  falls  far  below  normal,  and  the  power  of  the 
heart  is  gradually  extinguished. 

That  the  rise  of  arterial  pressure  must  be  largely  the  result  of  a  stimu- 
lant action  upon  the  heart  or  upon  the  vessel-walls  is  shown  by  the  finding 
of  Bezold  and  Gotz,  that  the  arterial  pressure  still  rises  under  the  influ- 
ence of  physostigmine  after  high-up  section  of  the  spinal  cord  ;  and  by 
that  of  Harnack  and  Witkowski,  that  when  the  vaso-motor  centres  are 
paralyzed  with  chloral,  physostigmine  causes  a  very  decided  increase  of  the 
arterial  pressure.  The  facts — that  section  of  the  vagi  does  not  interfere 
with  the  production  of  the  cardiac  phenomena  of  Calabar  bean,  and  that 
in  the  frog  physostigmine  acts  in  its  usual  way  on  the  heart,  although 
the  brain  and  medulla  have  been  destroyed  (Vintschgau) ;  also  that 


*  We  have  not  seen  the  original  paper  of  these  authorities  in  the  Centralblalt fur 
Med.  Wissenschaft,  1867,  but  quote  them  from  the  paper  of  Arnstein  and  Sustschinsky. 


DEPRESSO-MOTORS.  233 

when  physostigmine  is  placed  directly  on  the  heart,  or  into  one  of  its 
chambers,  it  causes  a  long  diastolic  pause,  followed  by  contractions,  inter- 
rupted by  pauses,  and  finally  by  resumption  of  regular  contractions,  or 
else  by  diastolic  arrest,  the  heart  still  retaining  its  power  of  responding 
in  an  embarrassed  manner  to  stimuli  (Fraser) — would  appear  to  demon- 
strate that  physostigmine  directly  affects  the  heart.  How  far  this  in- 
fluence is  upon  the  cardiac  ganglia  and  how  far  upon  the  muscle-fibre 
has  not  been  determined.  It  seems,  however,  probable  that  physostig- 
mine affects  the  cardiac  muscles  in  the  same  way  as  it  does  the  muscles 
of  voluntary  life. 

There  is,  however,  much  reason  for  believing  that  physostigmine 
affects  the  peripheral  inhibitory  apparatus,  although  the  evidence  is  not 
entirely  clear.  Arnstein  and  Sustschinsky  found  in  rabbits  and  also  in 
guinea-pigs  that  the  influence  of  galvanic  irritation  of  the  vagi  upon  the 
heart  is  much  greater  after  than  before  poisoning  with  physostigmine, 
diastolic  arrest  being  produced  much  more  easily  and  continuing  much 
longer  than  normal  after  the  withdrawal  of  the  stimuli.  Moreover,  after 
having  completely  paralyzed  the  peripheral  cardiac  vagi  in  the  rabbit  by 
large  doses  of  atropine,  they  restored  functional  power  to  these  nerves  by 
injections  of  Calabar  bean.  If  the  accuracy  of  these  experiments  be  ad- 
mitted, it  must  also  be  admitted  that  physostigmine  is  a  powerful  stimulant 
to  the  peripheral  cardiac  inhibitory  apparatus.  Kohler,  however,  using 
the  frog,  and  Rossbach  and  Frohlich,  using  the  rabbit,  failed  to  resusci- 
tate the  atropinized  vagi  by  means  of  Calabar  bean,  but  a  negative  result 
in  such  a  case  might  be  due  to  an  improper  proportion  in  the  doses  of 
the  counter-poison,  or  to  the  atropine  being  employed  in  overwhelming 
amount. 

Physostigmine  appears  to  have  no  paralyzing  effect  upon  the  vagi  ;  at 
least  in  warm-blooded  animals  these  nerves  are  never  paralyzed  (Fraser, 
Arnstein  and  Sustschinsky,  Harnack  and  Witkowski)  ;  and  the  loss  of 
functional  power  which  has  been  detected  by  Fraser,  Rossbach  and 
Frohlich,  Harnack  and  Witkowski,  in  the  vagi  of  the  frog  does  not  ap- 
pear until  so  long  after  the  cessation  of  respiration  that  it  is  very  probably 
a  secondary  result. 

That  Calabar  bean  does  not  affect  the  cardiac  inhibitory  centres  would 
seem  to  follow  from  the  experiments  of  Arnstein  and  Sustschinsky,  in 
which  an  injection  of  the  drug  through  the  carotid  into  these  centres 
failed  to  affect  at  once  the  rate  of  the  heart. 

The  question  as  to  the  effect  of  physostigmine  upon  the  blood-vessels 
cannot  at  present  be  positively  answered.  Evidence  concerning  it  has 
been  brought  forward  by  Fraser  and  Harley  in  the  form  of  observations 
made  upon  the  web  of  the  frog.  We  have  already  stated  our  belief  that 
this  sort  of  evidence  is  of  very  little  value.  In  the  present  instance,  as 
usual,  it  is  entirely  contradictory  as  given  by  different  observers.  (For 
details,  see  tenth  edition  of  this  treatise. ) 

The  fact  that  the  rise  of  arterial  pressure  produced  by  physostigmine 


234  GENERAL    REMEDIES. 

after  section  of  the  cord  is  not  nearly  so  great  as  in  an  uninjured  animal 
suggests,  but  does  not  prove,  that  the  drug  affects  the  vaso-motor  centre. 
Analogy  makes  it  probable  that  the  muscular  fibres  in  the  coats  of  the 
vessels  share  the  wide-spread  muscular  action  of  the  poison,  and  that  the 
peripheral  contraction  of  the  arteries  is  an  efficient  cause  in  producing 
rise  of  blood-pressure.  In  considering  the  general  physiological  action 
of  the  drug,  it  must  not  be  forgotten  that  its  influence  upon  the  heart  is 
entirely  subservient  to  its  influence  on  the  nervous  system,*  and  that 
death  in  the  mammal  occurs  before  the  stage  of  cardiac  palsy  is  reached, 
unless  the  drug  be  injected  directly  into  the  heart  in  overwhelming  dose. 

Blood. — According  to  Fraser,  after  death  from  physostigmine  the 
blood  coagulates  slowly  and  loosely,  and  the  red  disks  present  various 
irregularities  of  outline  ;  it  is  probable  that  these  changes  are  due  to  the 
long  asphyxia,  and  that  the  poison  does  not  directly  affect  the  blood. 

Intestines. — Intestinal  peristalsis  is  primarily  much  increased  by  the 
action  of  Calabar  bean  (Westermann,13  Papi,  Fraser).  After  poisonous 
doses  there  is  at  first  a  stage  of  exceedingly  active  movements  in  the 
bowels  ;  then  spasmodic  tetanic  contraction  of  the  intestines  occurs,  so 
that  their  calibre  is  very  much  diminished  ;  and  finally  relaxation  and 
dilatation  take  place.  After  death  the  vermicular  movements  are  found 
very  much  lessened  (Fraser)  or  altogether  abolished  (Tachau).  The 
action  of  Calabar  bean  upon  the  intestines  appears  to  be  peripheral,  due 
to  contact  of  the  poison  in  the  blood  with  the  muscular  fibres  or  the 
nerve- elements  in  the  walls  of  the  bowels  ;  for  Westermann  found  that 
extirpation  of  the  cardiac  ganglion  had  no  effect  upon  the  action  of  the 
drug,  but  that  tying  of  the  mesenteric  and  of  the  cceliac  arteries,  before 
poisoning,  prevented  any  increase  in  the  peristalsis. 

Secretion. — Calabar  bean  probably  increases  intestinal  secretion.  Its 
action  upon  the  salivary  glands  is  often  decided,  and,  according  to  Heiden- 
hain,  is  not  prevented  by  atropine. 

Eye. — The  contraction  of  the  pupil  which  is  produced  by  Calabar 
bean  is,  without  reasonable  doubt,  caused  by  a  local  peripheral  influence. 
The  fact  that  physostigmine  will  contract  the  atropinized  pupil  is  relied 
upon  by  Schmiedeberg "  to  prove  that  the  action  of  physostigmine  is 
directly  upon  the  iris  muscle  ;  a  deduction  which  seems  unwarranted. 
As  well  argue  that  atropine  acts  upon  the  muscle  because  it  antagonizes 
physostigmine. 

The  closeness  of  the  analogy  between  the  pupillary  action  of  atropine  and  that 
of  physostigmine  is  seen  in  the  fact  that,  like  the  former,  the  latter,  as  shown  by 
the  experiments  of  Ve'e  and  Leven 15  on  chickens,  does  not  affect  the  irides  of 
birds.  It  is  probable  that  the  two  alkaloids  are  directly  antagonistic  in  their 
action  upon  the  peripheral  nerve-endings  in  the  pupil. 

It  has  been  held  by  various  authorities  that  if  galvanization  of  the  sympathetic 

*  For  a  discussion  of  the  peculiar  cardiac  relations  of  physostigmine  and  muscarine, 
see  the  paper  by  Harnack  and  Witkowski.  Those  authors  believe  that  Calabar  bean  sets 
in  motion  the  heart  arrested  in  diastole,  not  by  paralyzing  the  cardiac  inhibitory  appa- 
ratus, but  by  stimulating  the  cardiac  muscle. 


DEPRESSO-MOTORS.  235 

fibres  in  the  neck  fails  to  expand  a  contracted  pupil,  the  myosis  must  be  due  to 
paralysis  of  the  sympathetic.  Evidently,  however,  this  is  asserting  too  much,  for,  as 
pointed  out  by  Griinhagen,16  it  is  conceivable  that  an  oculo-motor  spasm  can  exist 
of  such  intensity  that  the  antagonistic  nerve  is  unable  to  dilate  the  pupil.  The  tes- 
timony as  to  whether  galvanic  stimulation  of  the  sympathetic  does  or  does  not 
dilate  the  physostigminized  pupil  is  somewhat  conflicting.  Schultz,33  and  Griin- 
hagen, each  affirms  that  dilatation  always  occurs  ;  whilst,  on  the  other  hand,  Gustav 
Engelhardt "  has  found  that  galvanization  of  the  cervical  sympathetic  has  no  effect 
upon  the  physostigminized  pupil.  The  experiments  of  Fraser,  of  Bernstein  and 
Dogiel,  and  of  Rosenthal 18  would  seem  to  reconcile  these  differences,  and,  by  their 
accord,  to  prove  that  under  the  maximum  influence  of  Calabar  bean  the  sympathetic 
nerve  is  powerless,  while  when  the  contraction  is  the  result  of  a  milder  influence  of 
the  drug,  stimulation  of  the  sympathetic  nerve  will  cause  some  dilatation.*  Fraser, 
and  also  Engelhardt,  have  found  that  if  the  poles  of  a  battery  be  applied  directly  to 
an  iris  even  most  profoundly  contracted  by  physostigma,  immediate  dilatation 
occurs. 

If  it  be  true  that  direct  stimulation  of  the  muscle-fibres  of  the  iris 
causes  dilatation  of  the  physostigminized  pupil,  whilst  stimulation  of  the 
sympathetic  nerve  fails  of  effect,  it  would  appear  that  Calabar  bean  par- 
alyzes the  sympathetic  nerve-endings  in  the  iris.  On  the  other  hand,  the 
well-known  force  of  the  myosis  indicates  that  it  is  not  due  simply  to  loss 
of  power  in  the  dilating  fibres  ;  an  indication  which  is  corroborated  by  the 
fact  that  section  of  the  cervical  sympathetics  will  not  produce  a  myosis 
as  complete  as  that  caused  by  physostigmine.  It  would  seem,  there- 
fore, that  the  whole  influence  of  Calabar  bean  is  a  simultaneous  stimula- 
tion of  the  oculo-motor  nerve-endings  and  paralysis  of  the  peripheral 
sympathetic  nerve-endings. 

The  observations  of  Rossbach  and  Frohlich,  that  overwhelming  doses 
of  physostigmine  finally  dilate  the  pupil,  have  been  confirmed  in  cases  of 
human  poisoning  (see  Leibholz).  It  would  seem,  therefore,  that  when 
the  alkaloid  is  in  sufficient  amount  the  primary  oculo-motor  stimulation  is 
followed  by  oculo-motor  palsy. 

SUMMARY. — The  dominant  physiological  action  of  Calabar  bean  is 
a  persistent  depression  of  the  motor  centres  of  the  spinal  cord,  involving 
also  the  respiratory  centres  in  the  medulla,  and  producing  loss  of  reflex 
action  -with  an  increasing  paralysis,  ending  in  death  from  centric  para- 
lytic asphyxia.  Contraction  of  the  pupil  is  usually  seen  in  the  poison- 
ing, and  is  always  produced  by  the  local  application  of  the  drug ;  it  is 
due  to  a  peripheral  influence  and  probably  to  paralysis  of  the  sympa- 
thetic nerve-filaments  with  stimulation  of  the  oculo-motor  nerve-end- 
ings. The  motor  nerve-trunks  are  scarcely  affected,  but  in  slow  poi- 
soning probably  suffer  some  depression  of  function  which  especially 
affects  their  peripheral  endings.  Neither  the  cerebral  cortex  nor  the 
sensory  nerve  nor  the  sensory  nerve-centres  are  acted  upon,  unless 
secondarily  in  the  latest  stages  of  poisoning.  Calabar  bean  acts  as  a 

*  More  recently  Rossbach  and  Frohlich  affirmed  that  galvanization  of  the  sympathetic 
still  causes  dilatation,  even  when  the  action  of  the  physostigmine  is  most  vigorous.  As  it 
is  scarcely  conceivable  that  the  various  other  investigators  should  have  been  so  much  in 
error,  it  is  probable  that  Rossbach  and  Frohlich  used  such  strong  currents  that  they  were 
directly  transmitted  to  the  iris. 


236  GENERAL    REMEDIES. 

stimulant  directly  either  upon  the  muscle  structure  itself  or  upon  the 
peripheral  nerve-endings  in  the  muscles.  The  influence  of  the  drug 
upon  the  circulation  is  entirely  subordinate.  Early  in  the  poisoning 
there  is  a  rise  of  the  blood-pressure,  -which  is  in  great  part,  if  not 
altogether,  due  to  a  direct  stimulation  of  the  cardiac  muscle  or  its 
contained  ganglia,  although  it  is  probable  (not  proved)  that  there  is 
some  contraction  of  the  blood-vessels,  -which  may  be  due  to  an  influ- 
ence upon  the  muscle-fibre  in  the  vessel-walls  similar  to  that  upon 
other  muscle-fibres,  striated  and  non-striated.  We  have  no  informa- 
tion as  to  the  effect  of  the  poison  on  the  vaso-motor  centre.  Accord- 
ing to  some  authorities,  the  peripheral  vagi  are  strongly  stimulated. 
Intestinal  peristalsis  is  greatly  increased  by  the  direct  action  of  Calabar 
bean  upon  the  muscular  fibres  or  the  peripheral  nerve-endings  in  the 
intestinal  -walls.  The  alkaloids  of  Calabar  bean  are  rapidly  absorbed, 
and  are  eliminated  chiefly  by  the  kidneys. 

THERAPEUTICS. — The  physiological  action  of  Calabar  bean  has  sug- 
gested its  use  in  spasmodic  affections,  in  atony  of  the  muscular  coats  of 
the  bowel,  and  in  various  diseases  of  the  eye. 

The  action  of  Calabar  bean  upon  the  spinal  cord  very  early  led  to  its 
use  in  spasmodic  affections,  and  especially  in  tetamis.  In  the  paper  of 
B.  Roemer19  are  collected  forty-seven  cases,  of  which  twenty  proved 
fatal.  To  these  we  are  able  to  add  the  twenty  whose  references  are  given 
below,*  making  in  all  sixty-seven  cases,  with  thirty-seven  recoveries  and 
thirty  deaths, — not  a  very  flattering  record. 

It  is,  however,  proper  to  state,  as  affecting  the  value  of  these  statistics, 
that  much  of  the  Calabar  bean  extract  which  has  been  offered  in  the 
market  is  practically  inert,  and  in  all  probability  in  some  of  these  cases 
the  drug  did  not  have  a  fair  trial  ;  and  that  when  especial  care  was  taken 
by  certain  observers  better  results  were  achieved,  although  on  so  small  a 
scale  as  to  leave  the  issue  in  much  doubt,  f 

In  trismus  neonatorum,  Calabar  bean  has  been  employed  with  results 
certainly  no  more  encouraging  than  those  obtained  in  tetanus.  In  chorea 
it  has  also  been  used  by  some  practitioners  with  asserted  advantage,  but 
further  experience  hardly  justifies  its  administration.20 

The  physiological  action  of  physostigmine  upon  the  unstriped  intestinal 
muscle-fibres  has  led  to  its  employment  in  atony  of  the  muscular  coat  of 
the  bowels  and  other  similar  organs.  V.  Subbotin 21  has  used  the  extract 

*  FATAL  CASES. — Fenwick,  one  (Glasgow  Medical  Journal,  1869,  300)  ;  Franzolin, 
one  (The  Doctor,  Oct.  i,  1871)  ;  Laborde,  one  (British  Medical  Journal,  June,  1872)  ; 
Valdivieso,  one  (Philadelphia  Medical  Times,  i.  455) ;  Tyson,  one  (Ibid.,  418) ;  Johnson. 
one  (Ibid.,  372) ;  one  (London  Lancet,  1874) ;  Silbermann,  one  (Charier' s  Thesis,  1881)  ; 
Delaraarre,  one  (Paris  Thesis,  1875);  Richelot,  one  (These  de  Concours,  1875).  RE- 
COVERIES.— Fenwick,  one  (Glasgow  Medical  Journal,  1869,300) ;  Newman,  one  (Medi- 
cal Examiner,  July,  1869) ;  W.  W.  Keen,  one  (Philadelphia  Medical  Times,  i.  195)  ;  J. 
H.  Packard,  one  (Ibid.,  138)  ;  Cunningham,  one  (British  Medical  Journal,  i.  1874) ;  one 
(Cincinnati  Lancet,  Sept.  1878).  All  these  cases  were  of  the  traumatic  form  of  the  dis- 
ease. Charier,  one  (Paris  Thesis,  1881)  ;  Burnam,  one  (Lancet,  Jan.  1881) ;  Pooley,  one 
(New  York  Med.Journ.,  Sept.  1878) ;  Silbermann,  one  (Charter's  Thesis,  1881). 

t  For  a  favorable  record,  see  Watson  (Glasgow  Medical  Journal,  N.  S.,  1869,  i.  54)  ; 
consult  also  London  Practitioner,  Sept.  1869- 


DEPRESSO-MOTORS.  237 

with  the  happiest  results  in  a  case  of  chronic  bronchial  catarrh  with  in- 
tense dyspnoea,  believed  to  be  due  to  weakness  of  the  bronchial  muscular 
fibres,  and  also  in  one  of  apparently  '  'phantom  tumor, ' '  with  chronic  in- 
testinal dyspepsia  and  catarrh.  In  constipation  dependent  upon  relaxa- 
tion, and  as  an  addition  to  laxative  pills,  we  have  found  it  very  useful. 
A.  Hiller  "  strongly  endorses  the  value  of  the  extract  in  chronic  intestinal 
atony,  after  or  during  a  catarrh,  in  the  convalescence  from  fever,  etc.,  and 
in  constipation  with  flatulence,  in  meteorism,  etc. 

Calabar  bean  has  also  been  employed  in  strychnine-poisoning,  and  a 
recovery  obtained  after  the  ingestion  of  three  grains  of  the  latter  alkaloid 
is  reported  by  J.  W.  Keyworth. 2S 

In  epilepsy,  some  trials  have  been  made  of  the  drug,  but  its  value  is 
very  doubtful.  Harnack  and  Witkowski  have  found  that  in  epileptic 
guinea-pigs  physostigmine  causes  a  succession  of  fits  lasting  for  hours  and 
days.  They  have  further  noted  a  similar  influence  upon  man.  Atten- 
tion has  also  been  called  to  the  employment  of  Calabar  bean  as  a  galac- 
tagogue™  the  extract  being  applied  to  the  breast  itself. 

The  Use  of  Eserine  in  Diseases  of  the  Eye.* — The  instillation  of  a 
drop  of  a  one-quarter  to  one-half  per  cent,  solution  of  eserine  sulphate 
into  the  eye  is  followed  by  strong  contraction  of  the  sphincter  of  the  iris 
and  by  spasm  of  the  ciliary  muscle  which  adapts  the  eye  for  the  near 
point.  Its  action  begins  in  about  one  minute,  usually  reaching  its  maxi- 
mum in  from  twenty  to  thirty  minutes,  and  lasts  from  twenty -four  to  thirty- 
six  hours.  The  intraocular  tension  is  reduced,  provided  it  has  been  raised 
above  the  normal  point  before  the  application  of  the  drug.  Eserine,  when 
first  instilled  into  the  eye,  is  apt  to  produce  twitching  of  the  eyelids  and 
sharp  supraorbital  pain  due  to  its  causing  spasm  of  accommodation.  It  is 
used  by  ophthalmologists  :  First,  to  reduce  abnormally  high  intraocular 
tension,  particularly  in  glaucoma,  and  in  those  ocular  conditions  in  which, 
other  things  being  equal,  it  is  desired  to  diminish  the  intraocular  tension  ; 
second,  to  prevent  prolapse  of  the  iris  after  simple  cataract  extraction,  and 
sometimes  to  reduce  a  prolapse  when  this  has  occurred  in  the  periphery 
of  the  cornea  as  the  result  of  an  operation  or  of  a  perforating  corneal  ulcer  ; 
third,  to  limit  the  progress  of  deep  ulcers  near  the  margin  of  the  cornea, 
because  it  is  supposed  to  promote  absorption  through  dilatation  of  the 
ciliary  vessels  and  to  check  the  sloughing  process  ;  fourth,  to  counteract 
the  effect  of  the  milder  acting  mydriatics, — for  example,  homatropine, — 
especially  in  eyes  in  which  their  use  has  tended  to  raise  intraocular  ten- 
sion ;  fifth,  to  overcome  paresis  of  the  ciliary  muscle  resulting  from 
various  diseases, — for  example,  diphtheria,  diabetes,  syphilis  ;  sixth,  to 
reduce  the  vascularization  in  certain  types  of  keratitis,  episcleritis,  and 
scleritis,  provided  there  be  no  associated  iritis.  Eserine  too  freely  used, 
especially  in  hyperaemic  eyes,  is  capable  of  causing  slight  iritis,  the  so- 
called  eserine  iritis.  If  the  indications  for  a  local  anaesthetic  are  present 

*  This  section  has  been  written  by  Professor  George  E.  de  Schweinitz. 


238  GENERAL  REMEDIES. 

in  conjunction  with  those  demanding  a  myotic,  there  is  no  objection  to 
combining  in  the  same  solution  eserine  and  cocaine,  or  eserine  and  dionine. 

ADMINISTRATION. — Calabar  bean  is  usually  administered  as  an  extract 
(EXTRACTUM  PHYSOSTIGMATIS,  U.  S. ),  the  commencing  dose  of  which  is 
one-tenth  to  one-fifth  of  a  grain  (0.0065-0.013  Gm. ).  The  dose  of  the 
tincture  (TINCTURA  PHYSOSTIGMATIS — ten  per  cent.,  U.  S. )  is  twenty 
to  forty  minums  (1.25-2.5  C.c. ).  The  alkaloid  is  preferable,  on  account 
of  its  certainty.  The  salicylate  (PHYSOSTIGMINE  SALICYLAS,  U.  S. )  is 
preferable  to  the  sulphate  (PHYSOSTIGMINE  SULPHAS,  U.S.)  as  more 
permanent,  the  sulphate  being  very  deliquescent.  The  thirtieth  of  a 
grain  (0.002  Gm. )  of  either  the  alkaloid  or  its  salt  may  be  considered  to 
be  the  full  dose. 

TOXICOLOGY. — So  far  as  we  know,  Calabar  bean  has  not  been  used, 
either  in  Europe  or  in  this  country,  with  criminal  intent.  In  Liverpool 
seventy  children  were  accidentally  poisoned  at  one  time.25  Many  of  the 
victims  vomited  spontaneously,  and  thus  relieved  themselves.  Those 
brought  to  the  hospital  were  in  a  state  of  extreme  prostration  and  muscular 
relaxation.  They  appeared  to  suffer  almost  no  pain,  some  of  them,  how- 
ever, saying  that  they  had  a  ' '  belly-ache. ' '  Among  some  thirteen  ex- 
amined, one  had  the  pupils  contracted.  The  only  child  who  did  not 
recover  was  excessively  weak,  and,  crying  out  suddenly,  was  dead  of 
syncope.  The  heart  was  found  relaxed  and  flabby,  both  sides  equally 
full  of  blood.  Half  a  bean  produced  in  a  strong  man26  great  muscu- 
lar weakness,  tightness  across  the  chest,  temperature  of  96.6°  F. ,  very 
slow,  intermittent,  irregular  pulse,  and  collapse,  without  vomiting,  purg- 
ing, contraction  of  the  pupils,  or  abdominal  pain.  Lodderstaedt 27  re- 
ports a  hypodermic  injection  of  one-half  a  milligramme  of  the  physo- 
stigmine  sulphate  in  a  boy  nine  years  old,  followed  in  a  quarter  of  an 
hour  by  violent  headache,  free  sweating,  salivation,  slowing  of  the  pulse, 
repeated  vomiting,  contraction  of  the  pupils,  and,  finally,  deep  collapse, 
from  which,  however,  the  patient  recovered.  Two  girls  took  between 
them  o.i  gramme  (1.53  grains)  of  physostigmine,  with  the  result  of 
sudden  unconsciousness,  great  redness  of  the  face,  muscular  relaxation, 
vomiting,  widely  dilated,  immovable  pupils,  and,  on  recovery  of  con- 
sciousness, violent  abdominal  pains,  with  pulse  60,  and  hard  ;  recovery 
after  some  hours  (Leibholz28). 

In  1864  Kleinwachter  first  used  successfully  atropine  in  Calabar  bean 
poisoning,  and  thereby  started  much  discussion  and  research. 

Bourneville M  detailed  in  1867  some  experiments  which  seemed  to  show  that 
there  is  a  real  antagonism  between  Calabar  bean  and  the  mydriatic,  and  in  1870 
published  five  experiments  upon  guinea-pigs,  which  were  very  decisive  in  that  a 
proved  fatal  dose  of  physostigmine  was  given  in  each  case  and  recovery  obtained 
by  the  use  of  non-lethal  doses  of  atropine.  In  1869  Roberts  Bartholow,  of  Cin- 
cinnati, on  the  strength  of  a  few  really  indecisive  experiments,  arrived  at  a  con- 
clusion opposite  to  that  of  Bourneville. 

In  an  extremely  thorough  research,  which  might  well  serve  as  a  model  to  any 
one  studying  the  antagonistic  action  of  poisons,  Fraser30  demonstrated  that  within 


DEPRESSO-MOTORS.  239 

certain  limits  atropine  may  be  relied  upon  as  a  counter-irritant  poison  to  physostig- 
mine.  He  found  that  in  the  rabbit  one-fiftieth  of  a  grain  of  atropine  could  success- 
fully antagonize  one  and  a  half  but  not  twice  the  minimum  fatal  dose  of  Calabar 
bean,  one-fortieth  of  a  grain  of  atropine  could  overcome  two  to  two  and  a  half  times 
the  minimum  lethal  dose  of  physostigmine,  and  three-fiftieths  was  sufficient  for 
three  times  the  minimum  fatal  dose.  When  four  times  the  lethal  dose  of  physo- 
stigmine was  given  to  the  rabbit,  atropine  was  powerless  to  do  good.  In  all  these 
cases  the  atropine  was  given  just  before  the  administration  of  the  Calabar  bean. 
\Yhen  the  atropine  was  given  five  minutes  after  the  physostigmine  the  largest  dose 
of  the  physostigmine  which  could  be  combated  successfully  was  three  times  the 
minimum  fatal  dose.  No  experiments  were  made  by  Fraser  to  test  the  value  of 
physostigmine  in  atropine-poisoning.  These  experiments  of  Fraser  *°  have  been  in 
some  degree  confirmed  by  the  imperfect  researches  of  Amagat.31 

The  antagonism  between  physostigmine  and  pilocarpine  is  at  least  as 
great  as  that  between  atropine  and  pilocarpine.  (  See  article  on  Jaborandi. ) 
The  practical  deduction  from  the  scientific  and  clinical  evidence  is  that  in 
any  case  of  Calabar  bean  poisoning  both  of  the  antagonistic  alkaloids 
should  be  used  in  doses  proportionate  to  the  amount  of  the  poison 
ingested. 

J.  Pal M  asserts  that  physostigmine  is  an  antidote  to  curare  ;  it  being 
possible  with  it  to  bring  about  voluntary  respiration  in  an  animal  which  has 
been  entirely  paralyzed  by  the  South  American  poison.  We  know  of  no 
experiments  as  to  the  value  of  curare  in  physostigmine-poisoning. 

POTASSII    BROMIDUM— POTASSIUM    BROMIDE.     U.S. 

Potassium  bromide  occurs  in  milk-white  cubic  or  quadrangular  pris- 
matic crystals  of  an  acrid  saline  taste,  freely  soluble  in  water  and  slightly 
so  in  alcohol.  When  its  solution  is  mixed  with  starch,  and  chlorine  is 
added,  a  yellow  color  is  developed.  A  bluish  tint  betrays  contamination 
with  an  iodide. 

PHYSIOLOGICAL  ACTION. — Local  Action. — When  a  solution  of  the 
bromide  is  applied  locally  to  the  heart,  it  produces  instantly  marked 
lessening  of  its  action,  and,  if  in  sufficient  amount  and  concentration, 
even  instantaneous  diastolic  arrest.1  Upon  the  voluntary  muscles  it  acts 
in  a  similar  manner  when  similarly  applied.  If  its  solution  be  not  too 
concentrated  or  abundant,  however,  the  muscle  of  the  frog  is  first  thrown 
into  a  tetanic  spasm,  and  Purser  suggests  that  the  tetanic  symptoms  seen 
in  the  frog  poisoned  by  potassium  bromide  are  due  to  this,  action  on  the 
muscles.  On  the  nerve- trunks,  and  also  on  the  nerve-centres,  the  bro- 
mide acts,  when  applied  locally,  as  a  paralyzing  poison  (Amory,2  Ringer 
and  Morshead3).  It  is,  therefore,  evident  that  potassium  bromide  in 
sufficient  quantity  is  a  poison  to  all  the  higher  animal  tissues.  In  general 
poisoning  of  animals  by  hypodermic  injection  of  the  bromide,  this  local 
action  is  often  very  manifest,  and  paralysis  of  the  part  into  which  the  solu- 
tion has  been  thrown  follows  very  rapidly  upon  the  injection. 

Potassium  bromide  is  distinctly  irritating,  and  when  in  the  form  of 
powder  it  is  affirmed  to  be  somewhat  caustic,  and  has  been  highly  recom- 
mended for  the  destruction  of  excessive  granulations,  etc. 


240  GENERAL  REMEDIES. 

Absorption  and  Elimination. — Potassium  bromide  is  freely  absorbed 
and  circulates  in  the  blood  as  a  bromide.  Elimination  takes  place  to  a 
certain  extent  through  the  skin,  and  probably  largely  through  the  intes- 
tinal mucous  membranes,  though  the  chief  avenue  is  the  kidney. 

P.  Guttmann  *  has  recognized  bromine  in  the  contents  of  the  acne  pustules  of 
bromism  ;  Bill 5  detected  the  bromide  in  marked  quantities  in  the  faeces  of  men 
taking  it ;  and  H.  Quincke6  found  that  when  forty  grains  of  sodium  bromide  were 
given  to  dogs  with  intestinal  fistula,  two  and  a  half  hours  afterwards  the  intestinal 
juices  were  free  from  the  bromide,  which  reappeared  in  them  three  to  six  hours 
later.  The  salt  has  been  found  by  Voisin,  Amory,  Namias,  Bill,  etc.,  in  the  saliva 
and  in  the  urine,  and  by  Amory 7  in  the  perspiration.  In  the  body  of  a  man  who 
died  while  taking  it,  M.  Namias 8  found  it  in  all  the  liquids,  as  well  as  in  the  brain, 
liver,  spinal  cord,  lungs,  etc.  The  rapidity  of  elimination  seems  to  vary :  thus, 
Amory  recovered  one-half  of  the  amount  ingested  during  the  first,  and  one-third 
during  the  second,  twenty-four  hours,  and  Ware  (Thesis  of  H.  P.  Bowditch)  ob- 
tained a  little  more  than  half  of  the  amount  ingested  in  the  urine  of  the  succeeding 
thirty-two  hours,  while  Bill  was  not  able  to  get  more  than  one-eighteenth  of  it 
during  the  first  day.  Bill  has  frequently  found  the  bromide  in  the  urine  two  weeks 
after  the  last  dose  had  been  exhibited  ;  and  Rabuteau  has  seen  its  presence  persist 
under  similar  circumstances  for  a  month.  According  to  T.  Hondo,10  when  the  diet 
is  rich  in  sodium  chloride  the  bromides  are  eliminated  much  more  freely  than  when 
common  salt  is  withheld. 

When  a  bromide  is  given  continuously  it  accumulates  in  the  body  and 
may  be  found  in  every  tissue,  but,  according  to  Doyon  and  Cazeneuve9 
(confirmed  by  Fere  and  Herbert10),  it  is  stored  up  in  the  nerve-centres 
much  more  largely  than  elsewhere. 

General  Action. — Potassium  bromide  administered  to  frogs  in  minute 
doses  produces  as  a  first  result  a  tetanoid  condition,  in  which  there  may 
be  very  marked  opisthotonos.  After  a  short  time  this  stage  of  muscular 
excitement  gives  way  to  one  of  great  muscular  relaxation  and  total  aboli- 
tion of  reflex  actions.  Voluntary  movements,  however,  often  occur 
during  this  period,  and  the  frog  which  has  been  lying  limp  and  appar- 
ently dead  will  startle  the  observer  by  a  sudden  vigorous  leap.  This  fact 
has  been  so  frequently  witnessed  that  there  can  be  no  doubt  of  its  truth.* 
Very  early  in  the  paralytic  stage  the  respiratory  movements  are  affected, 
and  they  gradually  grow  less  until  their  final  arrest.  When  a  very  large 
dose  of  the  bromide  is  given,  death  may  be  induced  by  paralysis  of  the 
heart  (Albert  Eulenberg  and  Paul  Guttmann11)  ;  but  after  a  small  toxic 
dose  this  viscus  continues  to  beat  long  after  the  cessation  of  breathing. 
If  the  drug  be  given  by  an  injection  practised  in  the  vicinity  of  the  heart, 
sudden  cardiac  arrest  always  occurs. 

Upon  mammals  12  (Eulenberg  and  Guttmann  ")  the  bromide  acts  very 
much  as  upon  frogs,  inducing  progressive  paralysis,  depression  of  tem- 
perature, and  death  by  asphyxia  when  given  in  small  poisonous  doses  ; 

*  It  is  vouched  for  by  the  following  observers :  J.  M.  Purser  (Dublin  Journ,  Med.  Set., 
1869,  xlvii.  324) ;  Lewisky  aus  Kazan  (  Virchozv's  Archiv,  1869,  xlv.  191)  ;  J.  V.  Laborde 
(Archives  de  Physiol.  Norm,  et  Palhol.,  1868,  i.  423,  and  Comptes-Rendus,  1867,  Ixv.)  ; 
Damourette  and  Pelvette  (Bull.  Thlrafi.,  1867,  Ixxiii.  249). 


DEPRESSO-MOTORS.  241 

and  great  disturbance  of  the  circulation,  with  finally  diastolic  arrest  of  the 
heart,  when  very  freely  administered. 

So  far  as  we  know,  no  fatal  case  of  acute  poisoning  by  potassium 
bromide  is  on  record.  In  our  own  experience  an  ounce  taken  by  mis- 
take by  a  young  adult  produced  violent  pain  in  the  oesophagus,  nausea 
with  a  little  vomiting,  great  thirst,  feeling  of  weight  in  the  head,  and  ex- 
cessive sleepiness,  which  lasted  for  three  days.  In  a  case  reported  by 
Dougall 1S  an  ounce  and  a  half  taken  within  twenty-four  hours  was  fol- 
lowed by  coma,  with  weak  pulse,  cold  extremities,  temperature  96.8°  F., 
total  abolition  of  the  reflex  action,  and  general  cutaneous  anaesthesia, 
followed  by  excessive  drowsiness  interrupted  by  periods  of  talking  de- 
lirium and  by  periods  of  rationality,  the  symptoms  gradually  subsiding 
during  a  fortnight. 

The  results  of  the  continuous  employment  of  large  doses  of  the  bro- 
mide, however,  demonstrate  that  it  acts  upon  man  as  upon  the  lower 
animals.  When  it  is  taken  with  sufficient  freedom  to  accumulate  in  the 
system,  a  conjunction  of  phenomena  known  as  bromism  arises.  The 
cerebral  symptoms  are  a  sense  of  mental  weakness,  heaviness  of  intellect, 
failure  of  memory,  partial  aphasia,  great  somnolence,  and  depression  of 
spirits.  With  these  there  may  be  decided  impairment  of  the  sensibility 
of  the  mucous  membranes  and  of  the  skin,  so  that  titillation  of  the  fauces 
may  be  without  effect,  and,  according  to  Puche,  even  heat  applied  to  the 
skin  calls  forth  no  complaint  ;  Huette  "  has  seen  in  some  cases  absolute 
anaesthesia  of  the  sclerotic  conjunctiva.  The  sexual  function  is  abolished. 
There  are  also  very  generally  fetid  breath  and  an  eruption  of  acne  which 
may  indeed  be  very  severe.  Of  course,  in  any  individual  case  of  bromism 
many  of  these  symptoms  may  be  wanting  ;  but  when  the  use  of  the 
remedy  is  persisted  in,  they  all  at  last  become  developed  in  an  intense 
degree.  In  the  words  of  Edward  H.  Clarke  : 

"  The  fetid  breath  becomes  nauseous  ;  oedema  supervenes  on  congestion  of  the 
uvula  and  fauces  ;  the  whispering  voice  sinks  into  aphonia  ;  sexual  weakness  de- 
generates into  impotence  ;  muscular  weakness  becomes  complete  paralysis  ;  reflex, 
general,  and  special  sensations  disappear  ;  the  ears  do  not  hear,  nor  the  eyes  see, 
nor  the  tongue  taste  ;  the  expression  of  hebetude  becomes  first  that  of  imbecility, 
then  that  of  idiocy  ;  hallucinations  of  sight  and  sound,  with  or  without  mania,  pre- 
cede general  cerebral  indifference,  apathy,  and  paralysis ;  the  respiration,  without 
the  stertor  of  opium  or  alcohol,  i§  easy  and  slow  ;  the  temperature  of  the  body  is 
lowered  ;  as  the  bromism  becomes  more  profound,  the  patient  lies  quiet  in  bed,  un- 
able to  move  or  feel  or  swallow  or  speak,  with  dilated  and  uncontractile  pupils,  and 
scarcely  any  change  of  the  color  of  his  skin  or  face." 

Death  has  been  attributed  to  the  continuous  use  of  the  bromide  in 
large  doses.  Thus,  Hameau  reports  the  case  of  a  young  woman  who 
took  four  and  a  half  pounds  during  the  course  of  ten  months,  and  while 
in  a  condition  of  cachexia,  with  yellowish  skin,  a  copper- colored  erup- 
tion upon  the  forehead,  colic,  gastralgia,  insomnia,  etc.,  suddenly  be- 
came greatly  prostrated,  and  had  delirium  with  profuse  sweats,  followed 

.  16 


242  GENERAL  REMEDIES. 

by  death  in  four  days.  Anton  Eigner15  details  the  case  of  a  woman  who 
took  five  pounds  in  less  than  a  year,  and  while  having  very  pronoun  ed 
symptoms  of  bromism  was  seized  with  delirium  and  suffered  from  hal- 
lucinations of  sight  and  hearing,  saying  that  she  was  being  poisoned,  and 
finally  died  of  pneumonia.  In  neither  of  these  cases  can  it  be  considered 
probable  that  the  bromide  was  the  direct  cause  of  death. 

Nervous   System. — The   persistence  of    voluntary  movement  in  the 
frog  after  the  abolition  of  reflex  actions  shows  that  the  influence  of  the 
drug  is  not  chiefly  exerted  upon  the  cerebral  centres  of  motor  impulse, 
nor  upon  those  cells  of  the  cord  which  originate  movement,  but  upon 
either  the  afferent  nerves  or  those  portions  of  the  cord  which  transmit  the 
impulse  from  these  nerves  to  the  cells  presiding  immediately  over  motion. 
This  is  confirmed  by  some  experiments  of  Lewisky,  in  which  it  was  shown 
that  previous  separation  of  the  cord  from  the  cerebrum  had  no  influence 
upon  the  action  of  the  bromide.      Both  he  and  Purser 16  also  found  that 
death  occurred  from  small  doses  before  the  motor  nerve-trunks  and  the 
muscles  had  lost  their  irritability  (confirmed  by  Saisson17).     This  being 
so,  the  question  arises  whether  the  paralysis  be  spinal  or  due  to  paralysis 
of  the  peripheral  afferent  nerves.     There  is  an  apparent  conflict  in  the  evi- 
dence upon  this  point.    Eulenberg  and  Guttmann  found  that  when  access 
of  the  poison  was  prevented  to  one  or  more  limbs  by  tying  the  arteries, 
reflex  actions  were  abolished  in  these  parts  as  rapidly  as  in  others.      Simi- 
lar results  have  been  obtained  by  Lewisky,18  by  Roberts  Bartholow,19  by 
Purser,*  and  by  Laborde.20     The  latter  observer  has  also  found  that  elec- 
trical stimulation  of  a  nerve  high  up  will  cause  violent  spasms  in  the  mus- 
cles directly  supplied  by  it,   although  it  may  be  unable  to  excite  the 
slightest  reflex  tremor.      On  the  other  hand,  Damourette  and  Pelvette 
assert  a  contrary  result.     Unfortunately,  they  do  not  give  the  details  of 
their  experiments.     They  state,   however,   that  if  the  lumbar  plexus  of 
vessels  be  tied  before  the  poisoning,  the  fore  feet  lose  their  reflex  activity 
before  the  hinder.     There  are  two  possible  methods  of  reconciling  their 
results  with  those  of  the  other  observers.      In  some  way  the  operation 
may  have  interfered  with  the  circulation  in  the  lower  part  of  the  cord,  and 
consequently  the  poison  have  reached  more  freely  the  upper  part  of  it 
and  acted  first  upon  it.     Again,  if  the  injection  was,  as  is  very  probable, 
thrown  into  the  anterior  portion  of  the  body,  the  poison  may  have  reached 
the  anterior  extremities  in  so  concentrated  a  form  as  to  have  acted,  as  it 
were,  locally  upon  their  nerves  and  muscles.     The  same  observers  in  an- 
other portion  of  their  memoir  show  that  the  solution's  of  these  salts  in  the 
frog  travel  rapidly  by  imbibition  ;  and  this  and  their  local  action  seem  to 
us  to  be  the  cause  of  the  differences  of   experimental  results.      It  seems 
well  established  that  cutaneous  anaesthesia  in  greater  or  less  degree  ac- 
companies the  loss  of  reflex  activity  ;   for,   as  Purser  says,  a  poisoned 

*  From  the  wording  of  his  memoir,  however,  it  is  doubtful  whether  Purser  performed 
the  experiment  himself. 


DEPRESSO-MOTORS.  243 

animal  quite  able  to  jump  submits  to  pinching,  pricking,  burning,  etc., 
without  moving.  Eulenberg  and  Guttmann  have  seen  the  same  thing  in 
some  rabbits.  Damourette  and  Pelvette21  have  noticed  a  condition  in 
which  electrical  stimulation  of  a  nerve-trunk  produced  marked  reflex 
action,  although  no  excitement  of  the  skin  supplied  by  the  afferent  fibres 
of  the  nerve  was  capable  of  doing  this,  showing  that  the  extremities  of 
the  sensitive  nerves  are  affected  before  the  trunks.  The  evidence  is,  we 
think,  sufficient  to  prove  that  potassium  bromide  affects  all  parts  of  the 
nervous  system  of  the  lower  animals,  but  that  the  cerebrum,  the  motor 
tract  of  the  cord,  and  the  efferent  nerves  are  the  last  portions  to  be 
affected  ;  that  the  most  sensitive  to  its  action  is  the  receptive  portion  of 
the  cord, — that  which  receives  and  transmits  reflex  impulses, — and  next 
to  this,  and  perhaps  almost  equally  susceptible  with  it,  are  the  peripheral 
ends  of  the  afferent  nerves. 

Upon  the  cerebrum  of  the  higher  animals  the  bromides  undoubtedly 
exert  an  influence,  and  the  researches  of  Albertoni M  have  thrown  much 
light  upon  the  usefulness  of  the  drug  in  epilepsy.  That  observer  found 
that  when  administered  to  dogs  the  bromide  depresses  very  markedly  the 
power  of  the  motor  zone  of  the  cerebral  cortex  to  respond  to  stimuli,  and 
to  give  forth,  on  decided  irritation,  epileptic  discharges  ;  it  was  also  dis- 
covered that  this  action  of  the  bromide  was  much  more  decided  when  there 
had  been  a  prolonged  saturation  of  the  system  with  the  drug  than  after  a 
single  large  or  even  toxic  dose.  According  to  the  researches  of  A. 
Crisafulli,31  the  action  of  the  bromides  upon  the  cells  of  the  cerebral  cortex 
is  so  powerful  that  vacuolization  and  other  demonstrable  changes  are 
produced  by  it.  The  intellectual  symptoms  of  bromism  show  that  in  man 
the  action  of  the  bromide  on  the  cerebral  cortex  is  more  marked  than  in 
the  lower  animals,  on  account,  no  doubt,  of  the  higher  cerebral  develop- 
ment. The  drug  in  other  respects  acts  upon  man  as  upon  lower  mam- 
mals, lowering  the  reflex  excitability  of  his  spinal  cord,  paralyzing  the 
ends  of  the  peripheral  nerves,  etc. 

According  to  the  researches  of  B.  Schulze,23  there  is  under  the  influ- 
ence of  the  bromide  a  decided  decrease  in  the  elimination  of  phosphorus, 
— an  indication  that  the  protoplasmic  molecular  changes  in  the  nervous 
system  are  lessened  by  the  drug. 

Circulation. — It  is  well  established  that  large  toxic  doses  of  the  bro- 
mide exert  a  direct  paralyzing  action  on  the  heart,  lessening  both  the  force 
and  the  frequency  of  the  beat,  and  finally  causing  diastolic  arrest.*  J.  G. 
Schouten  M  found  that  during  the  slow  injection  of  a  two  per  cent,  solu- 
tion into  the  vena  cava  of  a  rabbit  the  cardiac  systole  grew  slower,  the 
diastolic  pauses  longer,  and  finally  the  heart  stood  still,  exhibiting  only 
fibrillary  contractions  of  its  walls.  The  same  observer  is,  so  far  as  we 
know,  the  only  one  who  has  made  manometrical  studies  of  the  action 
of  small  doses  of  the  drug.  He  found  that  such  amounts  of  the  bromide 

*  For  experiments  upon  the  isolated  frog's  heart,  see  Med.-Chir.  Trans.,  1882. 


244  GENERAL  REMEDIES. 

administered  hypodermically  or  by  the  stomach  always  produced  in- 
creased pulse-frequency  with  lessened  arterial  pressure. 

It  would  appear,  therefore,  that  even  small  doses  of  potassium  bro- 
mide are  directly  depressant  to  the  circulation.  The  fall  of  the  arterial 
pressure  is  certainly  largely  of  cardiac  origin.  It  is  probable,  though  not 
proved,  that  the  vaso-motor  system  also  shares  the  paralyzing  influence 
of  the  drug.  How  far  the  base  in  potassium  bromide  is  responsible  for 
the  cardiac  action  has  never  been  determined. 

Temperature. — In  warm-blooded  animals,  toxic  doses  of  potassium 
bromide  lower  very  decidedly  the  temperature.  There  have  been  no 
calorimetric  experiments  to  determine  whether  this  fall  of  temperature  is 
due  to  a  diminished  heat-production  or  an  increase  in  heat-elimination. 
The  relaxed  condition  of  the  vaso-motor  system  under  the  influence  of 
the  bromide  favors  the  escape  of  heat,  and  it  is  probable  that  the  fall  of 
bodily  temperature  is  due  in  part  or  altogether  to  an  excessive  loss  of 
heat. 

Nutrition. — The  symptoms  of  bromism  show  that  potassium  bro- 
mide has  a  distinct  influence  upon  the  general  nutrition  of  the  body,  and 
it  would  appear  probable  that  on  account  of  the  potassium  in  it  there 
would  be  an  increase  in  tissue-waste.  The  results  reached  by  investiga- 
tors are,  however,  distinctly  conflicting,  although  in  many  ways  they 
appear  to  be  the  a  priori  expectation. 

It  should  be  further  recognized  that  we  have  no  knowledge  whatsoever 
as  to  the  general  influence  of  bromine  upon  the  tissue- changes. 

Rabuteau  K  found  that  while  taking  the  bromide  there  was  slight  lessening  in 
the  daily  elimination  of  urea.  The  experiment  was,  however,  a  single  one,  and 
the  daily  dose  of  the  bromide  was  only  fifteen  grains,  an  amount  so  small  as  to  have 
no  determinate  influence.  H.  Bill,  in  an  elaborate  study  of  the  action  of  the  bro- 
mides upon  elimination,  determined  that  there  was  a  very  decided  decrease  in  the 
amount  of  carbonic  acid  thrown  off  from  the  lungs,  but  that  the  elimination  of  urea 
was  not  sensibly  affected.  On  the  other  hand,  the  quantity  of  urine  was  usually 
increased,  the  coloring-matters  invariably  augmented,  and  the  action  on  phosphoric 
acid  varied  :  after  smaller  doses  it  appeared  to  be  slightly  increased.  Schulze, 
whose  article  we  have  seen  only  in  abstract,  in  an  apparently  very  careful  investiga- 
tion on  his  own  person,  found  as  the  result  of  the  ingestion  of  one  hundred  and 
fifty  grains  of  bromide  a  day  that  the  urinary  secretion  was  greatly  increased,  the 
phosphorus  diminished,  the  sulphur  very  much  increased,  and  the  nitrogen  slightly 
increased.  The  experiments  of  Chittenden  and  Culbert 26  were  made  with  the 
maximum  dose  of  one  hundred  and  fifty  grains  a  day.  They  found  diminished 
excretion  of  phosphorus,  but  a  pronounced  increase  of  urea.  In  Chittenden  and 
Culbert's  experiments  ammonium  bromide  acted  like  potassium  bromide,  but  more 
powerfully,  so  far  at  least  as  the  urea  was  concerned.* 

*  It  has  been  asserted  (Binz,  London  Pract.,  1874)  that  potassium  bromide  owes  its 
physiological  and  therapeutic  powers  solely  to  its  base.  This  is  plainly  not  the  case, 
as  the  bromide  is  not  largely  decomposed  in  the  system,  and  the  symptoms  caused  by  it 
are  very  different  from  those  produced  by  potassium  carbonate :  in  a  later  publication 
(Arch.  f.  Exper.  Path.  Tlierap.,  xiii.)  Binz  himself  has  shown  that  bromine  vapor  pro- 
duces in  frogs  effects  in  many  respects  similar  to  those  caused  by  the  potash  salt.  At 
the  same  time  it  is  almost  certain  that  the  potash  influences  the  system  to  some  extent. 


DEPRESSO-MOTORS.  245 

SUMMARY. — When  in  sufficient  concentration  potassium  bromide 
acts  as  a  powerful  depressant  upon  all  of  the  higher  tissues.  It  is 
absorbed  rapidly  and  eliminated  in  all  the  secretions  more  slowly; 
so  that  when  given  continuously  it  accumulates  and  causes  bromism, 
usually  first  manifested  by  fetid  breath,  acne  eruption,  sleepiness,  mus- 
cular relaxation,  and  general  depression.  The  portions  of  the  human 
organism  most  sensitive  to  its  influence  are  the  whole  cerebral  cor- 
tex, the  receptive  side  of  the  spinal  cord,  and  the  afferent  peripheral 
nerve-endings.  The  influence  of  potassium  bromide  upon  the  circula- 
tion is  subordinate  to  its  action  on  the  nervous  system.  In  full  dose, 
however,  it  is  directly  depressing  both  to  the  heart  and  to  the  blood- 
vessels, and  we  have  no  knowledge  that  it  acts  in  any  dose  as  a  stimu- 
lant either  to  the  heart  or  the  vaso-motor  system.  The  fall  of  temper- 
ature which  has  been  noted,  chiefly  in  the  lower  animals,  after  toxic 
doses  of  the  bromide  is  in  all  probability  due  to  extreme  heat-dissi- 
pation, in  turn  the  outcome  of  vaso-motor  depression. 

THERAPEUTICS. — Potassium  bromide  is  employed  by  the  therapeutist 
to  quiet  cerebral  excitement  when  not  inflammatory  in  its  nature  ;  to  lessen 
over-susceptibility  of  the  spinal  centres  of  reflex  action,  or  of  the  periph- 
eral afferent  nerves  which  lead  to  these  centres  ;  and  to  subdue  nervous 
excitement  of  the  genital  system. 

The  bromides  are  contra-indicated  by  an  excessive  irritability  of  the 
gastro-intestinal  mucous  membrane  ;  when  such  condition  exists  they 
may  provoke  exhausting  diarrhoea.  Great  exhaustion,  and  especially 
great  nutritive  exhaustion  of  the  nerve-centres,  is  a  centra-indication  to 
their  use.  Thus,  owing  to  the  excitement  that  attends  confusional 
insanity, — i.e. ,  the  insanities  following  child-birth,  typhoid  fever,  surgical 
operations,  etc., — bromides  are  frequently  administered  in  large  doses,  to 
the  great  detriment  of  the  patient.  We  are  well  convinced  that  under 
such  circumstances  they  greatly  lower  the  nutrition  and  check  recovery. 
In  the  same  way,  in  cerebral  softening,  senile  dementia,  and  allied  dis- 
orders, they  must  be  used,  if  at  all,  only  with  the  greatest  reserve. 

There  are  various  forms  of  nervous  excitement,  or  unrest,  such  as 
sometimes  follow  excessive  intellectual  toil,  anxiety,  and  other  nervous 
strain,  or  occur  during  convalescence  from  acute  disorder,  in  which  the 
salt  now  under  consideration  is  very  valuable.  The  same  may  be  said 
of  some  forms  of  hysteria.  In  some  cases  of  neuralgia  the  bromide 
affords  great  relief,  but  in  the  majority  of  cases  it  fails.  It  has  seemed 
to  us  useless  in  neuralgia  dependent  upon  anaemia  or  want  of  power  ; 
and  our  experience  agrees  with  that  of  Anstie,  that  it  is  especially  useful 
in  persons  of  good  nervous  power,  muscular  force,  and  activity  of  circu- 
lation. As  an  hypnotic,  it  is  employed  in  wakefulness  from  nervous  ex- 
citement and  in  delirium  tremens,  but  is  of  very  feeble  power. 

G.  Krosz  (Arch./.  Exper.  Path.  Therap.,  vi.  43),  in  three  experiments  upon  man,  found 
decided  difference  in  the  results  produced  by  proportionate  doses  of  potassium  bromide 
and  of  sodium  bromide.  He  attributes  the  lessening  of  reflex  activity  to  the  bromine 
(see  also  Steinauer,  Vlrchow's  Archiv,  lix.). 


246  GENERAL  REMEDIES. 

The  chief  use  of  the  bromide  is  to  lessen  motor  activity.  It  is 
especially  in  epilepsy  that  it  has  attained  a  well-deserved  reputation, 
doing  far  more  good  than  all  other  remedies  combined,  sometimes  ap- 
parently effecting  cures,  more  commonly  ameliorating  the  symptoms,  _but 
occasionally  failing  entirely.  There  is  no  known  method  of  distinguish- 
ing before  trial  with  any  certainty  in  what  cases  it  will  do  good.  The 
assertion  of  Trousseau,  that  it  is  least  efficient  in  the  mild  form  of  the 
disorder  known  as  petit  mal,  accords  with  our  experience.  The  most 
brilliant  results  have,  as  a  rule,  been  obtained  in  cases  of  not  too  long 
duration  in  which  the  fits  were  frequent  and  severe.  The  governing 
principle  in  its  use  is  to  try  it  in  every  case,  increasing  the  dose  until  a 
mild  degree  of  bromism  is  induced,  and  being  guided  by  the  results. 

The  salt  is  also  often  efficacious  in  various  reflex  spasmodic  neuroses  : 
in  the  vomiting  of  pregnancy  or  of  uterine  diseases ;  in  the  gastric  con- 
vulsions of  children  ;  and,  according  to  J.  T.  Rothrock,  in  preventing  the 
so-called  urethral  fever  induced  in  very  susceptible  males  by  the  intro- 
duction of  the  catheter  or  bougie,  it  is  very  useful.  The  physiological 
action  of  the  salt  seemingly  indicates  that  it  is  one  of  the  remedies  best 
suited  for  the  treatment  of  tetanus.  Clinical  experience  certainly  accords 
with  this  conclusion  :  in  a  table  published  in  previous  editions  of  this 
treatise  were  collected  thirty-four  cases  of  tetanus,  nearly  all  traumatic, 
treated  chiefly  by  potassium  bromide,  with  but  four  deaths.  Not  less 
than  a  half-ounce  of  the  salt  should  be  exhibited  in  the  day,  and  at  night 
chloral  should  be  used  as  an  hypnotic.  (See  CHLORAL.) 

In  strychnine-poisoning,  Saisson  has  demonstrated  the  value  of  the 
bromide  by  experiments  on  animals,  and  Charles  B.  Gillespie '"  and  C.  L. 
Bard 28  have  each  reported,  under  its  use,  recovery  without  vomiting  after 
the  ingestion  of  three  grains  of  the  alkaloid. 

In  nervous  excitement  connected  with  the  genital  function,  potassium 
bromide  is  often  of  value.  When  there  is  actual  inflammatory  disease, 
as  in  gonorrhoea,  the  drug  frequently  fails  to  effect  the  desired  end. 
If,  however,  there  be  no  organic  lesion  of  the  organs  or  of  their  nerve- 
centres,  the  continued  dose  will  usually  succeed  to  a  greater  or  less  extent. 
We  have  found  the  remedy  effective  in  cases  of  semi- impotence  from 
over- irritability  of  the  organs  causing  emission  too  soon  during  attempted 
sexual  congress.  There  is  abundant  evidence  as  to  its  value  in  nympho- 
mania.  As  an  adjuvant  to  other  physical  and  moral  measures  of  relief, 
the  salt  may  be  used  with  satisfaction  in  men  suffering  from  masturbation. 
In  nervous  symptoms  occurring  at  the  time  of  the  menopause  or  compli- 
cating uterine  disease,  and  in  the  peculiar  train  of  morbid  phenomena 
arising  from  the  forced  suppression  of  the  sexual  function  in  vigorous 
individuals  of  either  sex  to  whom  circumstances  have  denied  marriage, 
the  bromides  have  almost  a  ' '  unique  power. ' ' 

Ch.  Bernard  **  affirms  that  potassium  bromide  in  doses  of  from  twenty 
to  forty-five  grains  a  day  removes  with  marvellous  quickness  malarial 
enlargements  of  the  spleen. 


DEPRESSO-MOTORS.  247 

ADMINISTRATION. — We  have  known  half  an  ounce  of  the  bromide  to 
be  taken  at  once  without  inducing  any  serious  symptoms  ;  and  in  severe 
acute  cases,  as  in  tetanus  and  strychnine-poisoning,  it  is  perfectly  safe  to 
administer  two-drachm  doses  at  short  intervals,  as  the  case  may  require. 
Almost  all  the  indications  for  the  use  of  the  bromide  are  best  met  by  the 
so-called  continuous  dose, — i.e.,  by  the  administration  of  so  much  in  the 
twenty-four  hours  until  an  effect  is  induced.  In  epilepsy,  from  one 
to  two  drachms  (4-8  Gm.)  may  be  exhibited  daily  (see  page  246); 
although  as  little  of  the  remedy  as  will  suffice  to  prevent  the  recurrence 
of  the  fit  must  be  used,  yet  any  amount  necessary  to  do  this  should  be 
given,  unless  distinct  bromism  be  produced  before  the  paroxysms  are 
arrested.  The  remedy  must  be  exhibited  in  a  freely  diluted  solution. 
In  some  cases  it  causes  diarrhcea,  which  may  generally  be  checked  with 
small  doses  of  opium.  It  is  essential  in  epilepsy  and  other  chronic  dis- 
orders to  persist  in  the  continuous  administration  of  the  bromide,  it  may 
be  for  years  ;  and  it  is  remarkable  how  rapidly  the  symptoms  of  long- 
continued  bromism  subside  upon  the  withdrawal  of  the  drug.* 

AMMONII    BROMIDUM— AMMONIUM    BROMIDE.     U.S. 

Ammonium  bromide  may  be  obtained  in  colorless  crystals,  but  gen- 
erally occurs  in  a  granular  powder,  which  becomes  yellowish  on  exposure. 
It  has  a  saline,  pungent  taste,  and  is  readily  soluble  in  water,  sparingly 
so  in  alcohol.  When  mixed  with  mucilage  of  starch,  if  chlorine- water  be 
added  it  becomes  yellowish  brown  ;  a  blue  tint  would  indicate  the  pres- 
ence of  iodine. 

PHYSIOLOGICAL  ACTION. — The  physiological  action  of  ammonium 
bromide  has  not  as  yet  been  fully  investigated  ;  but  our  present  knowl- 
edge indicates  that  in  many  points  it  resembles  that  of  the  corresponding 
salt  of  potassium,  whilst  in  others  it  differs  from  the  latter.  According 
to  N.  Bistroff1  when  two  decigrammes  are  administered  to  a  frog,  a 
period  of  quietude  and  lessened  irritability  is  induced,  which,  after  fifteen 
or  twenty  minutes,  gives  place  to  violent  tetanic  convulsions.  Later, 
all  excitability  is  lost,  so  that  even  burning  calls  forth  no  recognition  ; 
the  frog  lies  in  whatever  position  it  is  placed  in,  the  spasms  become  more 
violent,  and  death  ensues.  Similar  phenomena  have  been  witnessed 
also  by  Amory *  in  the  rabbit  and  the  guinea-pig,  although  in  one  of 
Amory's  experiments  the  guinea-pig  died  without  convulsions  having 
been  noted.  The  curious  abolition  of  reflex  action  and  of  sensibility  con- 
sentaneously with  the  occurrence  of  violent  convulsions  was  noted  fre- 
quently, and  death  seems  always  to  have  resulted  from  asphyxia.  In  the 

*  Ch.  Fere  asserts  that  many  of  the  disagreeable  symptoms  of  bromism  are  due  to 
its  disturbance  of  the  alimentary  canal,  and  are  prevented  by  the  daily  exhibition  of 
four  grammes  of  beta-naphtol  and  four  grains  of  bismuth  salicylate,  which  doses  are 
borne  for  months  without  any  inconvenience,  usually  with  much  benefit  to  the  appetite 
and  digestion  (Nouv.  Iconog.  de  la  Salp&tr.,  1890). 


248  GENERAL  REMEDIES. 

experience  of  Bistroff,  moderate  non-fatal  doses  produced  only  weakness 
and  uncertain  movements  in  the  rabbit. 

Ammonium  bromide  appears  to  exert  very  little  influence  upon  the 
peripheral  motor  apparatus.  Amory  has  seen  the  nerves  retain  their 
power  of  conduction  after  having  been  placed  in  a  "  strong  solution  ;' ' 
and,  according  to  Bistroff,  muscles  retain  their  irritability  after  soaking 
five  minutes  in  a  ten  per  cent,  solution.  According  to  the  latter  observer, 
the  heart  always  continued  beating  after  death  from  the  drug,  and  the 
heart  removed  from  the  batrachian  and  laid  in  a  ten  per  cent,  solution  did 
not  in  any  degree  lose  its  normal  activity.  Even  a  twenty  per  cent,  so- 
lution dropped  upon  the  bared  heart  produced  only  a  momentary  arrest 
of  the  ventricular  systole.  On  the  other  hand,  Purser  asserts  that  the 
heart  is  soon  arrested  in  diastole  in  poisoning  by  this  salt,  and  that  the 
nerves  and  muscles  also  lose  their  irritability  sooner  than  after  poisoning 
by  potassium  bromide. 

The  subject  certainly  needs  further  investigation  ;  yet  it  seems  to  us 
probable  that  ammonium  bromide  exerts  less  influence  upon  the  cardiac 
and  other  muscles  than  does  potassium  bromide,  but  that  in  other  respects 
their  actions  are  very  similar.  The  experiments  of  Amory  indicate  that 
the  ammonium  salt  affects  temperature  and  acts  on  the  capillaries  in  the 
same  way  as  that  of  potassium,  and  that  it  is  also  eliminated  in  a  similar 
manner.  The  experiments  of  Bistroff  show  that  in  the  cat,  at  least,  am- 
monium bromide  -has  no  especial  influence,  as  has  been  asserted,  upon 
the  superior  laryngeal  nerves. 

THERAPEUTICS. — Ammonium  bromide  is  capable  of  fulfilling  all  the 
indications  for  which  potassium  bromide  is  used,  and  is  especially  useful 
in  epilepsy.  (See  Strontium  Bromide.} 

SODIUM  BROMIDE,  U.  S. ,  closely  resembles  in  appearance  potassium 
bromide,  and  has  been  supposed  by  Voisin  to  have  very  similar  physio- 
logical and  therapeutic  properties.  On  the  other  hand,  M.  J.  V.  Laborde  * 
states  that  in  double  the  toxic  dose  of  potassium  bromide  he  has  found 
that  it  does  not  produce  any  characteristic  symptoms  in  the  frog,  the 
guinea-pig,  or  the  dog,  and  leaves  the  animal  perfectly  healthy. 

By  clinicians  the  drug  has  been  used  to  a  considerable  extent.  Mere- 
dith Clymer 2  asserts  that  it  will  arrest  epilepsy  without  producing  the 
unpleasant  cerebral  symptoms  of  bromism.  He  gives  twenty  grains 
three  times  a  day.  Hammond s  asserts  that  in  epilepsy  it  is  in  no  wise 
superior  to  the  potassium  salt,  but  affirms  that  its  hypnotic  power  is  much 
greater.  M.  E.  Decaisne,4  as  the  result  of  the  trial  of  the  drug  in  twenty- 
seven  cases  {epilepsy,  chorea,  hysteria},  asserts  that  its  action  is  the  same 
as  that  of  the  potassium  salt,  except  that  instead  of  causing  diarrhcea  it 
constipates.  Notwithstanding  this  testimony,  our  own  experience  is  in 
accord  with  the  physiological  teachings,  that  sodium  bromide,  although 
not  free  from  therapeutic  value,  is  not  equal  to  potassium  bromide  in 
subduing  nervous  excitation,  and  is  in  no  wise  superior  to  it. 


DEPRESSO-MOTORS.  249 

LITHIUM  BROMIDE,  U.  S. ,  was,  we  believe,  first  employed  in  medi- 
cine by  Gibb,1  who  recommended  it  as  gently  toxic  and  sometimes  diu- 
retic. He  used  it  in  very  small  doses.  Attention  was  first  called  to  its 
employment  in  nervous  affections  by  S.  Weir  Mitchell,2  who  stated,  as 
the  result  of  his  experience,  that,  when  administered  to  the  amount  of  half 
a  drachm  to  one  drachm  daily,  it  acts  in  some  cases  of  epilepsy  after 
potassium  bromide  has  failed,  and  that  it  is  generally  efficient  in  about 
one-half  the  dose  of  that  salt ;  also  that  its  hypnotic  action  is  much  more 
decided.  Clark  confirms  these  observations  ;  but,  according  to  our  ex- 
perience, the  drug  has  no  especial  value. 

STRONTII  BROMIDUM.  U.  S. — Strontium  bromide  occurs  in  colorless, 
odorless,  very  deliquescent  crystals  of  a  bitter  saline  taste,  soluble  in  1.05 
parts  of  water.  Strontium  bromide  shares  the  action  of  the  other  stron- 
tium salts  upon  the  alimentary  canal  and  of  other  bromides  upon  the 
nervous  system.  It  is  therefore  an  extremely  useful  remedy  in  the 
treatment  of  epilepsy.  It  yields  its  bromine,  however,  rather  slowly  to 
absorption,  and  we  have  found  that  it  usually  acts  much  better  in  con- 
junction with  ammonium  bromide  than  it  does  by  itself.  The  mixture  of 
the  two  bromides,  also,  is  much  better  tolerated  than  is  the  ammonium 
bromide  alone  ;  so  that  after  long  trials  in  many  hundreds  of  cases  of 
epilepsy  we  have  reached  the  conclusion  that  the  best  possible  results  are 
in  the  majority  of  cases  to  be  obtained  by  the  administration  of  a  mixture 
containing  in  each  dose  twenty  grains  of  ammonium  bromide,  ten  grains 
of  strontium  bromide,  five  grains  of  antipyrin,  and  three  minims  of  Fow- 
ler's solution,  given  morning  and  evening.  In  individual  cases  the  dose 
of  the  bromides  in  this  mixture  is  to  be  increased  or  decreased,  the  in- 
tent being  to  use  as  small  an  amount  of  the  bromides  as  possible  to  control 
the  paroxysms,  and  under  no  circumstances  to  go  beyond  the  production 
of  mild  bromism.  As  the  bromides  act  by  accumulation  in  the  system, 
and  as  patients  become  very  much  disgusted  by  the  long  continuance  of 
frequent  doses,  it  is  usually  much  better  to  give  the  drug  in  two  large 
than  in  three  smaller  doses  a  day. 

CALCII  BROMIDUM.  U.S. — Calcium  Bromide  is  a  white,  granular,  very 
deliquescent  salt,  of  a  sharp,  saline  taste,  soluble  in  half  part  of  water.  It 
is  undoubtedly  effective  in  epilepsy,  and,  according  to  Germain  Se'e,1  is 
absorbed  and  eliminated  rapidly,  and  acts  favorably  upon  the  digestion. 
Dose,  ten  to  twenty  grains  (0.66  to  1.33  Gm. ),  always  given  in  solution. 

ACIDUM  HYDROBROMICUM  DILUTUM.  U.  S. — Diluted  Hydrobromic 
Acid, — A  clear,  colorless,  strongly  acid,  odorless  liquid,  which  contains 
ten  per  cent,  by  weight  of  the  gas,  absolute  hydrobromic  acid.  In  the 
physiological  studies  of  E.  T.  Reichert,1  hydrobromic  acid  was  found  to 
produce  a  temporary  elevation  of  the  blood-pressure,  which  was  attributed, 
without  proof,  to  vaso-motor  spasm  of  peripheral  origin.  Large  doses 


25o  GENERAL  REMEDIES. 

were  directly  paralyzant  to  the  heart  and  to  a  less  extent  to  the  voluntary 
muscles.  Reflex  action  is  suspended  by  the  acid  in  the  frog,  and  all 
portions  of  the  spinal  cord  and  nerves  are  depressed  by  the  poison  ;  but 
Reichert  presents  experimental  facts  which  indicate  that  the  sensory  por- 
tions of  the  cord  and  the  sensory  nerves  are  affected  before  the  motor 
system  by  hydrobromic  acid  as  they  are  by  ordinary  bromides.  In  a  very 
thorough  test  of  hydrobromic  acid  in  a  large  number  of  hospital  epileptics, 
made  by  H.  C.  Wood,  it  was  found  that  hydrobromic  acid  in  equivalent 
doses  resembles  potassium  bromide  in  its  therapeutic  action,  and  is  less 
apt  to  produce  acne  eruption  or  muscular  depression.  It  was  determined, 
however,  that  the  acid  is  so  irritant  that  the  stomach  will  not  bear  full 
doses  of  it,  and  that  it  ought  to  be  used  only  in  combination.  The  official 
dose  is  one  fluidrachm  (4  C.c. ). 

Comparative  Power  of  Bromides. — It  is  probable  that  the  activity  of 
the  bromide  is  in  direct  proportion  to  the  amount  of  bromine  which  it 
contains.  It  is  interesting,  therefore,  to  note  that  the  calcium  bromide 
contains  eighty  per  cent,  of  bromine  ;  the  sodium  bromide,  seventy- 
seven  and  one-half  per  cent.  ;  the  potassium  bromide,  sixty-seven  per 
cent.  ;  the  strontium  bromide,  sixty-five  per  cent.  A  drachm  of  dilute 
hydrobromic  acid  is  equivalent  to  nine  grains  of  potassium  bromide. 

GOLD  BROMIDE. — The  original  assertion  of  Goubert,  that  gold  bromide  is 
exceedingly  valuable  in  the  treatment  of  epilepsy  and  migraine,  was  apparently 
experimentally  confirmed  by  Shtcherbak,  who  found  that  the  salt,  in  doses  of  o.  I 
to  0.2  gramme  per  kilogramme,  had  a  very  pronounced  effect  in  inhibiting  the 
psycho-motor  centres.  It  is  plain,  however,  that  one-eighth  of  a  grain  (8  Mg. )  of 
the  gold  bromide  (Goubert's  dose)  contains  too  little  bromine  for  that  element  to 
have  any  effect.  A  grain  of  the  gold  bromide  given  daily  has  produced  in  our 
experiences  no  perceptible  effect  in  epilepsy. 

BROMOFORMUM.  U.  S. — Bromoform.  Formyl  Bromide. — This  is  a  colorless 
liquid  with  an  ethereal  odor  and  sweetish  taste,  which,  first  brought  forward  in 
1849  by  Nunneley  and  Schuchard  as  an  anaesthetic,  was  found  too  dangerous 
for  use  as  such,  but  has  been  employed  to  a  considerable  extent  internally  in  the 
treatment  of  whooping-cough  and  other  diseases  for  which  the  bromides  are  used. 
It  is  probably  broken  up  in  the  system,  but  its  products  are  eliminated  with  great 
slowness.  It  is  undoubtedly  capable  of  acting  like  the  bromide,  but  has  no  advan- 
tage over  the  older  preparations  and  is  distinctly  more  dangerous.  W.  Gerhardi *  * 
has  shown  that  bromoform  is  capable  of  producing  wide-spread  fatty  degeneration 
in  the  lower  animals.  E.  Kiwull  *  has  collected  twenty  cases  of  poisoning  by  it ; 
the  symptoms  have  been  pallor,  titubation,  dilatation  of  the  pupil,  coma,  heart- 
failure,  and  collapse.  The  dose  for  the  adult  is  six  or  seven  drops  in  capsules. 

Two  substances,  apparently  parallel  in  that  they  are  saturated  solutions  of  bro- 
mine in  oil  and  in  that  the  bromine  is  stated  to  be  in  combination  with  olein,  have 
been  put  upon  the  market  by  manufacturers,  and  are  probably  identical  in  their 
physiological  influence. 

Bromolein  is  a  clear,  yellow,  oily  liquid,  said  to  contain  twenty  per  cent,  of 
bromine  in  oil  of  sweet  almonds. 

*  See  also  Wien.  Med.  Jahrb.,  1883,  497.  For  poisoning,  see  Times  and  Register, 
1892;  also  Annals  of  Gyn&cology,  1896-97;  Pest.  Med.-Chir.  Presse,  1897. 


DEPRESSO-MOTORS.  251 

Bromipin  is  a  similar  liquid,  prepared  with  bromine  and  sesame  oil,  and  sup- 
plied to  the  market  by  the  manufacturers  in  two  strengths,  one  containing  ten,  the 
other  thirty-three  and  one-third  per  cent,  of  bromine. 

According  to  Merck's  report,  thirty  grains  of  the  stronger  bromipin  are  equal 
to  fifteen  grains  of  potassium  bromide  ;  so  that  thirty  grains  of  bromolein  should  be 
considered  about  equal  to  ten  grains  of  potassium  bromide.  Of  the  weaker  bromi- 
pin one-half  ounce  may  be  given  as  dose  to  the  adult,  representing  theoretically 
twenty-four  grains  of  bromide. 

These  substances  may  be  used  hypodermically,  or  may  be  employed,  diluted 
with  oil,  endermically.  After  either  method  of  administration  bromine  soon  appears 
in  the  urine.  They  have  been  recommended  by  various  clinicians  in  epilepsy, 
insomnia,  neurasthenia,  and  other  diseases  in  which  the  bromides  are  commonly 
employed.  The  dose  of  either  substance  appears  to  be  in  direct  proportion  to  the 
amount  of  bromine  contained. 

CAMPHOR  A  MONOBROMATA.  U.  S. — Monobromated  Camphor  or  Bromated  Cam- 
phor.— This  is  a  compound  in  which  one  atom  of  hydrogen  in  the  camphor  has  been 
replaced  by  bromine.  It  occurs  as  a  crystalline  solid,  or  in  large  acicular  crystals 
several  inches  long. 

Our  present  knowledge  of  the  physiological  properties  of  bromated  camphor 
rests  upon  the  work  of  Bourneville,1  of  Lawson,2  of  Pathault,3  of  Richard  Peters,4 
and  of  Pellicani.5  In  frogs  there  is  progressive  loss  of  reflex  excitability  and  of 
voluntary  movement  (Peters),  which,  according  to  Pellicani,  is  due  to  paralysis  of 
the  motor  nerves.  Death  is  caused  by  arrest  of  respiration  (Peters).  In  mammals 
it  produces  violent  convulsions,  muscular  weakness  passing  almost  into  paralysis, 
reduction  of  temperature  (after  small  doses  preceded  by  a  rise — Peters),  great 
decrease  in  the  rate  of  the  respiration  and  of  the  pulse  (with  occasional  periods  of 
hurried  respiration — Peters),  profound  sleep  or  stupor,  and  finally  death.  Bourne- 
ville states  that  the  blood-vessels  of  the  eyes  and  ears  are  diminished  in  calibre. 
Upon  man  the  drug  probably  acts  as  upon  other  warm-blooded  animals  ;  in  a  case 
reported  by  M.  Rosenthal,6  forty-five  grains  of  it  caused  tremblings,  marked  slow- 
ing of  the  pulse,  and  coma  of  six  hours'  duration. 

Bromated  camphor  was  first  introduced  by  Deneffe7  as  a  nervous  sedative,  and 
as  an  antispasmodic,  especially  in  delirium  tremens,  but  is  of  little  value  ;  it  is  still 
used  in  hysteria,  and  has  an  especial  reputation  in  sexual  excitement  and.  spermator- 
rhoea. It  is  taken  with  difficulty,  and  is  apt  to  irritate  the  stomach.  It  is  too  irri- 
tant for  hypodermic  use.  Dose,  five  to  ten  grains  (0.3-0.6  Gm. ),  in  capsule  or 
coated  pill,  and  repeated  as  necessary. 

BROMOCOLL  is  a  yellow,  tasteless,  odorless  powder,  said  to  contain  twenty  per 
cent,  of  bromine,  ten  per  cent,  of  water,  thirty  per  cent,  of  gelatin,  and  forty  per 
cent,  of  tannic  acid.  According  to  the  experiments  of  Brat l  bromocoll  is  very 
resistant  to  gastric  juice,  but  is  readily  dissolved  with  decomposition  in  the  intes- 
tinal juices.  It  is  alleged  to  act  like  the  older  bromides  and  to  produce  less  dis- 
agreeable symptoms.  Friedlander 2  experimentally  determined  that  it  depresses  the 
irritability  of  the  psycho-motor  centres.  Dose,  thirty  to  seventy-five  grains  a  day. 

BROMALIN  {Bromethylformin}  occurs  in  colorless  scales  or  as  a  white  powder, 
nearly  tasteless  and  readily  soluble  in  water.  It  has  been  used  in  epilepsy  and 
therapeutically  allied  diseases,  especially  by  J.  Kollarits,1  and  found  to  have  no 
advantages  over  the  older  bromine  preparations.  The  dose  is  about  half  that  of 
potassium  bromide. 

For  a  resume  of  the  physiological  action  of  bromal  hydrate,  which  is 
certainly  valueless  as  a  practical  medicine,  see  the  tenth  edition  of  this 
treatise. 


252  GENERAL  REMEDIES. 

AMYL  NITRIS— AMYL  NITRITE.*     U.  S. 

Amyl  nitrite  was  discovered  by  the  French  chemist  Balard  in  1844, 
and  the  attention  of  physiologists  was  called  to  it  in  1859  by  Guthrie  ; 
but  it  was  not  until  1865  that  Richardson,  of  London,  introduced  it  to 
the  notice  of  the  profession.  It  is  a  yellowish,  oily,  very  volatile  liquid, 
of  a  very  penetrating,  persistent,  fruity  odor,  ' '  containing  eighty  per 
cent,  of  amyl  (principally  iso-amyl)  nitrite."  (U.  S.  P.).  It  is  prepared 
by  the  action  of  nitric  acid  on  amylic  alcohol,  or,  as  it  is  commonly 
called,  fusel  oil. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Amyl  nitrite  has  no  irri- 
tating properties.  It  causes  a  progressive  loss  of  functional  power  in  every 
highly  organized  tissue  with  which  it  comes  in  contact.  Nerve-centres, 
peripheral  nerves,  muscles  of  organic  and  voluntary  life,  all  succumb  to 
it  alike.  If  the  contact  be  not  continued  too  long,  the  tissue  may  recover 
even  after  a  total  suppression  of  its  function, — a  proof  that  the  poison  ex- 
erts no  destructive  chemical  or  devitalizing  influence  upon  the  tissues, 
such  as  that  of  sulphuric  acid  or  veratria. 

Absorption  and  Elimination. — Amyl  nitrite  is  absorbed  with  extraor- 
dinary rapidity,  especially  through  the  lungs,  and  must  also  be  eliminated 
from  or  destroyed  in  the  system  with  great  rapidity  on  account  of  the 
fugaciousness  of  its  action.  F.  Rohrmann *  believes  that  the  nitrites 
undergo  oxidation  in  the  system,  because  he  has  found  that  when  potas- 
sium nitrite  is  administered  to  the  lower  animals  it  appears  in  the  urine 
as  potassium  nitrate. 

General  Action. — The  most  prominent  symptoms  induced  when  amyl 
nitrite  is  inhaled  by  a  man  in  moderate  quantities  are  a  sense  of  great  ful- 
ness and  distention  of  the  head,  amounting  at  last  to  sev  :re  pain,  and  ac- 
companied by  intense  flushing  of  the  face,  a  deep,  labored  respiration,  and 
an  exceedingly  rapid,  violent  action  of  the  heart.  The  succession  of  these 
phenomena  is  usually  so  rapid  that  often  they  seem  to  be  simultaneous  ; 
but  it  is  said  that  the  cardiac  disturbance  is  sometimes  very  distinctly 
manifest  before  the  other  symptoms.  It  has  been  noticed  by  Peck  and 
confirmed  by  Ladendorf  that  objects  look  yellow  to  a  person  fully  under 
the  influence  of  the  drug.  After  poisonous  doses  the  symptoms  have 
been  great  pallor,  usually  dilatation  but  sometimes  contraction  of  the 
pupils,  excessive  muscular  relaxation,  slow,  scarcely  perceptible  pulse, 
haemoglobinuria,  and  irregular  respiration. 

In  the  lower  animals  the  first  stage  of  the  action  is  like  that  just 
described  in  man.  After  this  the  breathing  becomes  violently  hurried 
and  panting,  progressive  muscular  weakness  and  diminution  of  reflex 

*  Berloni's  ether  or  tertiary  amyl  nitrite,  a  mixture  of  amyl  nitrite  and  iso-butyl 
nitrite  has  been  found  by  Lauder  Brunton  and  T.  J.  Bokenham  to  act  very  much  as  does 
the  ordinary  amyl  nitrite,  except  that  its  effects  are  somewhat  more  slowly  developed 
and  are  more  permanent.  It  is  not  proved  to  be  more  stable  than  the  ordinary  amyl 
nitrite  and  has  no  advantages  over  the  latter.  According  to  Dunstan,  amyl  nitrite  of 
commerce  is  chemically  a  mixture  of  a  and  ft  amyl  nitrites,  iso-butyl  nitrite,  ethyl  nitrite, 
and  propyl  nitrite  (St.  Bartliolomew's  Hospital  Report,  28,  1892). 


DEPRESSO-MOTORS.  253 

activity  ensue,  and  finally  death  from  failure  of  respiration,  sensation, 
and  consciousness  being  preserved  almost  to  the  last.  A  very  peculiar 
symptom  is  that  a  long  time  before  death  both  the  arterial  and  the  venous 
blood  become  of  a  nearly  uniform  chocolate  color.  Convulsions  are  some- 
times present ;  but  in  our  experience  more  often  the  animal  is  exceedingly 
quiet  throughout  the  poisoning. 

Nervous  System. — The  influence  of  amyl  nitrite  upon  the  cerebrum  is 
very  feeble,  disturbances  of  intellection  and  of  consciousness  not  being 
produced  except  by  very  decided  toxic  doses,  and  not  being  prominent 
symptoms  of  the  poisoning.  As  was  shown  by  H.  C.  Wood,2  the  lessen- 
ing of  reflex  activity  and  of  voluntary  motion  which  undoubtedly  occurs 
in  toxaemia  from  the  agent  now  under  consideration  is  chiefly  spinal  in  its 
origin,  since  after  death  the  nerves  and  muscles  preserve,  though  in  an 
impaired  condition,  their  functional  power.  On  the  motor  centres  of  the 
cord  the  nitrite  acts  as  a  direct  and  powerful  depressant,  at  the  same  time 
that  it  exerts  a  similar  but  much  less  pronounced  influence  on  the  nerves 
and  muscles,  decreasing,  but  not  destroying,  their  functional  life.  The 
diminution  of  reflex  activity  is  never  preceded  by  a  stage  of  functional 
excitement.  In  some  animals  convulsions  do  occur,  especially  when  the 
drug  is  administered  by  inhalation  ;  but  they  are  in  all  probability  cere- 
bral, not  spinal,  and  due  to  the  asphyxiating  influence  of  the  poison. 
Over  the  sensory  nerves  and  centres  amyl  nitrite  has  but  little  power. 
They  are  among  the  last  portions  of  the  body  to  be  affected,  sensation 
being  intact  until  near  death  :  so  that  the  drug  is  in  no  sense  an  anaes- 
thetic. 

Respiration. — It  is  certain  that  the  respiratory  centres  are  greatly 
depressed  by  full  doses  of  amyl  nitrite,  the  breathing  becoming  both  slow 
and  shallow,  and  death  finally  occurring  from  centric  paralytic  asphyxia. 
Mayer  and  Friedrich  assert  that  small  doses  of  amyl  nitrite  increase  the 
rapidity  and  depth  of  respiration  by  stimulating  the  respiratory  centres  ; 
but  this  remains  at  present  doubtful,  it  being  probable  that  the  increased 
respiration  is  secondary  to  the  disturbance  of  the  circulation,  as  is  asserted 
by  Winkler. 

Circulation. — Although  the  pulse  may  be  much  increased  in  frequency 
sometimes  from  the  very  beginning  by  amyl  nitrite,  the  arterial  pressure 
is  diminished,  and  finally  is  reduced  almost  to  zero,  the  fall  of  pressure 
occurring  equally  after  section  of  the  vagi  as  at  other  times.  As  the  num- 
ber of  heart-beats  in  the  uninjured  animal  is  increased  rather  than  di- 
minished, while  the  strength  of  the  individual  beat  is  not  perceptibly 
lessened,  it  is  evident  that,  at  least  in  the  early  stages  of  the  poisoning,  the 
diminution  of  arterial  tension  is  not  cardiac  in  origin,  but  must  be  due  to 
dilatation  of  the  capillaries.  This  conclusion  is  confirmed  by  an  experi- 
ment of  Brunton,  who  found  that  if  the  descending  aorta  were  tied  high 
up,  no  perceptible  fall  of  pressure  was  produced  by  the  inhalation  of  the 
amyl  salt  until  very  late  in  the  poisoning,  when  the  heart  itself  was  acted 
upon  by  the  drug  ;  also  by  the  fact  noted  by  Amez-Droz*  and  by  Gaspy,* 


254  GENERAL  REMEDIES. 

that  the  vessels  of  the  rabbit's  ear  and  of  the  frog's  web  can  be  seen  to 
dilate  when  the  salt  is  inhaled.*  In  man  the  flushing  of  the  face  and  of 
the  retina,  as  noted  by  Charles  Aldridge,5  indicates  that  the  nitrite  acts 
locally,  probably  upon  some  centre,  before  it  does  generally,  as  general 
dilatation  of  the  vessels  causes  pallor. 

An  interesting  question  which  here  arises  is,  whether  the  dilatation  is 
centric,  due  to  an  action  on  the  vaso-motor  nerve-centres,  or  peripheral, 
due  to  a  direct  action  on  the  muscular  coat  of  the  arterioles.  We  be- 
lieve that  it  must  be  peripheral,  and  not  centric,  in  its  origin,  since  both 
in  our  own  experiments  and  in  those  of  Brunton  it  occurred  after  the  arte- 
rioles had  been  separated  from  the  vaso-motor  centres  by  division  of  the 
cord.  This  fact  appears  to  prove  that  the  fall  of  arterial  pressure  is  due  to 
a  direct  paralyzing  action  of  the  drug  upon  the  coats  of  the  arterioles, — 
a  conclusion  confirmed  by  our  knowledge  of  the  local  action  of  the  nitrite 
upon  muscular  tissue. 

Bernheim,  however,  asserts  that  this  cannot  be  so,  and  that  the  dilatation  must 
be  solely  due  to  an  action  upon  the  vaso-motor  centres,  because  he  found  that  gal- 
vanization of  the  cervical  sympathetic  still  caused  contractions  in  the  vessels  of  the 
ear  of  a  rabbit  to  which  amyl  nitrite  had  been  given.  As  pointed  out  by  Pick,6 
Bernheim's  experiment  does  not  warrant  his  conclusion.  It  only  shows  that  the 
muscle-fibres  in  the  walls  of  the  vessels  are  not  so  completely  paralyzed  as  to  be 
unable  to  respond  to  very  powerful  stimuli.  W.  Filehne 7  also  dissents  from  the 
view  that  the  action  of  the  nitrite  is  upon  the  vessels.  It  is  very  probable  from  the 
general  sedative  effect  of  the  drug  upon  the  motor  centres  that  it  acts  also  upon 
the  vaso-motor  centres  ;  and  when  the  local  flushings  caused  by  small  doses  of  the 
poison  are  borne  in  mind,  this  probability  is  greatly  enhanced.  Filehne  affirms  that 
when  to  animals,  whose  lungs  are  exposed,  inhalations  of  the  nitrite  were  given,  the 
change  of  color  was  not  nearly  so  great  as  in  the  ears,  and  that  if  the  sympathetic 
had  been  destroyed  in  the  neck  of  a  rabbit,  and  amyl  nitrite  exhibited,  the  ves- 
sels on  the  unwounded  side  actually  became  larger  than  those  of  the  opposite  ear. 
The  answer  to  these  results  is,  that  opening  the  chest  must  derange  most  profoundly 
the  pneumonic  circulation,  and  that  all  observations  upon  the  comparative  size  of 
vessels  are  very  apt  to  be  mere  guess-work  when  the  change  is  slight.  Moreover, 
in  Schuller's8  experiments,  after  destruction  of  the  cervical  sympathetic  in  a  rabbit, 
inhalations  of  the  nitrite  produced  still  further  dilatation  of  the  vessels  of  the  ear. 

Atkinson 9  and  D.  J.  Leech 10  have  each  found  that  the  nitrite  enor- 
mously increases  the  flow  of  blood-serum  which  is  being  forced  by  a 
steady  pressure  through  the  decapitated  tortoise,  or  through  a  recently 
excised  kidney  ;  a  solution  i  in  10,000  had  a  distinct  effect  in  widening 
the  blood-paths.  In  conclusion,  it  seems  to  us  established  that  amyl 
nitrite  does  act  locally  on  the  coats  of  the  arterioles,  although  it  may  at 
the  same  time  influence  the  vaso-motor  centres. 


*  A  noteworthy  fact  asserted  by  Amez-Droz  is  that  after  a  long  period  of  dilatation 
the  vessels  contract  again,  whether  the  inhalation  be  continued  or  not.  We  think  the 
explanation  of  this  is  simply  that,  owing  to  the  volatility  of  the  nitrite,  it  soon  all  escapes 
from  the  dossil  of  lint  on  which  it  is  placed  for  inhalation  ;  an  explanation  strongly  con- 
firmed by  a  statement  of  Amez-Droz,  that  in  these  cases  a  new  inhalation  was  followed  by 
dilatation  as  before.  Amez-Droz  says  only  the  arterioles  dilate,  but  Gaspy  found  that 
both  arterioles  and  veins  were  affected. 


DEPRESSO-MOTORS.  255 

In  man  the  pulse-rate  is  enormously  increased  by  amyl  nitrite.  In 
animals  the  amount  of  the  increase  varies,  but  in  the  higher  groups  the 
rule  appears  to  be  increase  of  the  pulse-rate,  which  is  especially  decided 
in  the  dog.  Filehne  has  by  a  single  very  ingenious  experiment  apparently 
shown  that  the  acceleration  is  due  to  a  depressing  influence  upon  the  in- 
hibitory centres.  He  divided  the  par  vagum  in  a  rabbit,  employed  an 
electric  current  to  the  sever  d  nerves  of  sufficient  strength  to  bring  the 
pulse-rate  to  normal,  and  found  that  the  amyl  salt  was  powerless  to  affect 
the  rapidity  of  the  cardiac  action.  Certain  experiments  performed  by 
Mayer  and  Friedrich  "  confirm  that  of  Filehne.  It  is  known  that  sudden 
asphyxia  slows  the  pulse  by  exciting  the  inhibitory  centre.  Mayer  and 
Friedrich  found  that  this  action  is  prevented  by  the  inhalation  of  the 
amyl  salt.  Then,  again,  they  found  that  when  by  compression  of  the 
arteries  the  blood  was  prevented  from  going  to  the  head,  the  nitrite  did  not 
increase  the  rapidity  of  the  pulse,  and  also  determined  that  the  reflex 
inhibitory  slowing  of  the  heart  by  irritation  of  a  sensitive  nerve  is  pre- 
vented by  amyl  nitrite.  Further,  in  dogs  with  a  powerful  cardiac  inhibi- 
tory apparatus  the  primary  influence  of  the  nitrite  is  more  marked  than  it 
is  in  rabbits,  whose  pneumogastrics  are  very  feeble.  The  sudden,  thump- 
ing action  of  the  heart  which  is  so  prominent  in  man  when  the  nitrite  is 
inhaled  is  therefore  probably,  at  least  in  part,  due  to  depression  of  the 
inhibitory  apparatus.  There  is,  however,  as  pointed  out  by  Reichert,12 
some  reason  for  believing  that  in  small  doses  the  nitrite  acts  primarily  as 
a  stimulant  to  the  heart.  Lauder  Brunton  long  ago  discovered  that  if  the 
aorta  be  compressed  so  as  to  eliminate  in  great  part  the  influence  of  the 
vaso-motor  system,  the  nitrite  causes  a  primary  rise  in  the  arterial  press- 
ure ;  and  it  is  perfectly  possible  for  an  excessive  heart-action  to  be  more 
than  neutralized,  so  far  as  the  arterial  pressure  is  concerned,  by  a  vaso- 
motor  depression,  so  that  the  immediate  fall  of  pressure  caused  in  the 
normal  animal  by  the  nitrite  is  not  proof  that  the  heart  may  not  be  stimu- 
lated. In  G.  A.  Atkinson's  experiments,  i  part  of  the  nitrite  in  20,000 
produced  a  slight  increase  in  the  working  power  of  the  cut-out  frog's 
heart  ( Williams' s  apparatus)  ;  i  in  10,000  caused  a  rise  for  four  or  five 
minutes,  followed  by  a  fall  ;  smaller  and  larger  amounts  than  these  had 
either  no  effect  or  lessened  the  heart's  action.*  It  seems,  therefore,  that 
our  present  physiological  evidence  justifies  the  belief  that  very  small  quan- 
tities of  amyl  nitrite  primarily  stimulate  the  heart,  although  it  is  demon- 
strated that  in  moderate  or  large  amounts  the  drug  respectively  depresses 
or  paralyzes  the  heart-muscle. 

Urine. — F.  A.  Hoffmann14  found  that  in  the  rabbit  a  hypodermic  in- 
jection of  o.  n  i  to  o.  1 1 3  gramme  of  the  drug  is  enough  to  cause  dia- 

*  There  is,  however,  still  much  uncertainty  about  the  matter.  D.  J.  Leech  affirms 
that  i  in  10,000  always  quickens  and  weakens  the  beat  of  the  isolated  frog's  heart  in  a 
Roy  apparatus.  In  a  single  experiment  made  with  amyl  nitrite  on  the  isolated  mam- 
malian heart,  Bock 13  came  to  the  conclusion  that  the  amyl  nitrite  has  no  effect  upon  the 
heart  itself.  The  experiment,  however,  does  not  seem  to  us  sufficient,  and  the  method 
employed  is  open  to  very  grave  objection. 


256  GENERAL  REMEDIES. 

betes.  If  twice  this  amount  of  the  amyl  salt  is  used,  the  sugar  becomes 
very  abundant  in  the  urine,  and  continues  to  be  present  for  from  twelve 
to  thirty  hours.  Consentaneously  with  the  elimination  of  sugar  there  is  a 
great  increase  in  the  amount  of  the  urine.  The  occurrence  of  glycosuria 
in  man  has  not  been  recorded  ;  it  is  produced  by  toxic  doses  only,  if  at  all. 
Temperature. — Amyl  nitrite,  in  whatever  way  exhibited,  if  given  in 
sufficient  amount,  reduces  most  remarkably  animal  temperature.  We  have 
seen  a  pigeon  perfectly  conscious  although  its  temperature  had  been 
brought  down  by  this  agent  some  13°  F.  This  influence  is  as  marked 
in  fever  as  in  the  normal  condition  of  the  animal,  and  is  independent  of 
the  nerve-centres,  occurring  after  section  of  the  cord,  and  even  after 
death  in  those  cases  in  which  post-mortem  rise  or  continuance  of  high 
temperature  normally  takes  place.  We  have  also  experimentally  deter- 
mined that  it  is  associated  with  diminished  excretion  of  carbonic  acid. 
It  must  therefore  be  due  to  a  direct  arrest  or  check  of  tissue-changes  or 
oxidation  within,  or  without,  the  blood.  The  mouth-temperature  in  man 
is  certainly  sometimes  elevated  by  the  inhalation  of  amyl  nitrite,  but 
the  rise  is  a  very  temporary  one.  W.  A.  Manassein  and  N.  Sassezki l* 
found,  in  a  number  of  studies  upon  normal  and  fevered  men,  that  while 
the  peripheral  temperature  was  at  first  increased  the  rectal  temperature 
was  always  reduced,  and  after  a  time  the  surface  of  the  body  grew 
cooler.  The  maximum  reduction  was  reached  in  one  to  one  and  a  half 
hours,  and  in  a  case  of  fever  amounted  to  3°  C. 

The  vapors  of  the  nitrite  have  a  very  marked  influence  over  oxida- 
tion outside  of  the  body,  as  is  shown  by  many  facts,  of  which  it  is  only 
necessary  here  to  cite  the  extinguishment  of  glowing  phosphorus  by  a 
few  drops  of  the  amyl  salt  diffused  through  the  jar.  It  cannot  be  doubted 
that  within  the  economy  the  same  thing  occurs.  If,  however,  the  arrest 
of  oxidation  were  complete,  instant  death  from  suffocation  would  result. 
The  true  explanation  of  the  symptoms  evidently  lies  in  diminution,  not 
destruction,  of  oxidation. 

When  an  animal  inhales  amyl  nitrite,  the  arterial  and  venous  blood 
soon  become  of  a  nearly  uniform  hue,  which  resembles  somewhat  that 
of  normal  venous  blood,  but  is  quite  distinct  from  it,  having  a  chocolate 
tint.  Moreover,  this  chocolate-colored  blood  does  not  assume  the  arterial 
hue  when  shaken  with  the  air. 

The  appearance  of  the  chocolate  color  of  the  blood  is  due  to  the  for- 
mation out  of  the  haemoglobin  of  a  new  substance  which  Gamgee 16  be- 
lieved to  be  a  nitrite-oxy haemoglobin,  but  which  has  been  considered  by 
most  observers,  on  account  of  similarity  of  spectrum,  to  be  the  methaemo- 
globin  of  Hoppe-Seyler."  Haldane,  Makgill,  and  Mavrogordato  "  assert, 
however,  that  the  spectra  are  not  absolutely  identical,  and  that  the  new 
compound  is  really  a  mixture  of  nitric-oxide-haemoglobin  and  haemoglobin. 

The  action  of  the  nitrites  upon  the  red  blood-corpuscles  immediately 
suggests  that  they  affect  the  animal  economy  by  overpowering  the  haemo- 
globin of  the  blood  and  putting  an  end  to  oxidation.  That  they  have 


DEPRESSO-MOTORS.  257 

an  influence  upon  the  interchange  of  gases  in  the  blood,  and  that  this 
influence  counts  for  much  in  their  action,  seems  certain.  On  the  other 
hand,  it  seems  almost  equally  certain  that  the  nitrites  in  therapeutic  doses 
do  not  arrest,  but  only  check  oxidation,  and  that  their  influence  upon 
the  nervous  system  and  circulation  is  independent  of  their  haemic  action. 

Gamgee  showed  conclusively  that  the  new  compound  in  the  blood  yields 
oxygen  to  a  reducing  agent,  and  that  when  nitrite  blood  is  brought  into  contact 
with  prepared  guaiacum-paper  it  still  oxidizes  it,  though  not  so  actively  as  normal ; 
so  that  evidently  the  blood-corpuscles  retain  to  a  greater  or  less  degree  their  power 
of  yielding  ozone  to  bodies  desiring  it,  and  are  capable  of  exerting  at  least  this  por- 
tion of  their  respiratory  function :  further,  when  this  ozone  is  given  up  and  the 
oxyhaemoglobin  changed  into  haemoglobin,  so  far  as  our  present  knowledge  goes, 
the  haemoglobin  must  absorb  more  oxygen  before  it  can  unite  with  the  nitrite. 
Evidently,  then,  absorption  of  oxygen  must  take  place  ;  evidently  the  blood-cor.- 
puscles  must  perform  their  respiratory  function  ;  but  evidently  also  they  are  greatly 
crippled  and  impaired  in  the  rapidity  and  ease  of  its  performance. 

Haldane,  Makgill,  and  Mavrogordato  found  that  when  an  animal  is  placed  in 
oxygen  gas,  under  a  pressure  sufficiently  high  to  so  saturate  the  serum  of  the  blood 
with  oxygen  that  it  (the  serum)  was  able  to  maintain  life,  ordinarily  fatal  doses  of 
the  nitrites  failed  to  kill,  although  by  increasing  the  amount  of  the  nitrite  death 
could  be  produced  ;  evidence  that  the  influence  of  the  nitrites  upon  oxidation  is  an 
important  but  not  a  sole  factor  in  their  toxic  influence.  Further,  Gamgee  showed 
that  potassium  and  other  nitrates  act  upon  the  blood  as  do  the  nitrites,  yet  the 
symptoms  caused  by  them  are  very  different  from  those  produced  by  the  nitrites. 
It  is  also  sure  that  various  drugs  in  toxic  doses  check  oxidation,  but  do  not  cause 
the  same  symptoms  as  are  produced  by  the  nitrites  ;  finally,  when  arrest  of  oxidation 
in  the  body  is  caused  by  substituting  oxygen  by  an  inert  gas,  such  as  nitrogen,  the 
symptoms  are  essentially  different  from  those  of  nitrite-poisoning,  the  brain  and  con- 
sciousness being  always  affected  before  the  spinal  centres,  whereas  under  the  influ- 
ence of  amyl  nitrite  the  contrary  occurs. 

In  sufficient  dose  amyl  nitrite  is  poisonous  to  the  white  corpuscles  ; 
Atkinson  has  found  that  i  in  1000  kills  the  corpuscles  in  from  fifteen  to 
twenty  minutes. 

SUMMARY. — The  dominant  physiological  action  of  amyl  nitrite  is 
upon  the  spinal  cord  and  the  circulation.  Under  its  influence  arterial 
pressure  falls  from  paralysis  of  the  blood-vessels,  chiefly  due  to 
a  direct  action  upon  the  muscles  in  their  •walls.  At  the  same  time 
the  vagi-centres  are  paralyzed  and  the  heart  is  stimulated  directly 
or  indirectly,  the  number  and  force  of  its  contractions  being  in- 
creased, this  period  of  stimulation  after  moderate  doses  gradually 
subsiding  into  the  normal  state,  but  after  toxic  doses  passing  into 
one  of  cardiac  paralysis,  -with  a  final  arrest  in  diastole,  -which  is  due 
to  a  direct  action  upon  the  heart-muscle  or  contained  ganglia.  Paral- 
ysis of  motion  and  loss  of  reflex  activity,  prominent  phenomena  of 
advanced  poisoning,  are  due  to  a  direct  action  upon  the  motor  side  of 
the  spinal  cord.  Death  results  finally  from  paralysis  of  the  respiratory 
centres.  By  a  direct  action  upon  the  red  blood-corpuscles  the  haemo- 
globin is  converted  into  a  new  compound,  probably  methaemoglobin. 
The  fall  of  the  bodily  temperature  is  probably  the  result  of  lessened 
oxidation.  Locally  applied  in  concentrated  form,  amyl  nitrite  paral- 
yzes all  higher  tissues. 

17 


258  GENERAL  REMEDIES. 

THERAPEUTICS. — Amyl  nitrite  is  employed  to  meet  indications  which 
are  very  closely  in  accord  with  its  known  physiological  action.  It  should 
be  remembered,  however,  that  its  influence  is  all  over  in  from  ten  to 
twenty  minutes  after  its  ingestion,  and  it  is  therefore  a  remedy  useful 
only  in  cases  of  crises  or  fugacious  conditions.  It  may  be  employed  in 
all  cases  in  which  it  is  desired  to  dilate  the  capillaries.  During  the  algid 
stage  of  an  ordinary  intermittent  fever  it  will  put  an  end  immediately  to 
the  chill,  but  does  not  affect  the  development  of  the  hot  stage.  It  might 
possibly  be  of  service  in  the  algid  stage  of  a  pernicious  malarial  fever. 

Led  by  the  evidences  of  arterial  spasm  in  the  sphygmographic  tracings 
in  a  case  of  angina  pectoris,  Lauder  Brunton  in  1867  suggested  its  use  in 
that  disease.  As  the  pathology  of  these  cases  of  heart-pang  is  not  defi- 
nitely made  out,  it  seems  useless  to  speculate  how  the  nitrite  acts  in 
many  cases  ;  but  there  is  abundant  evidence  of  its  value  in  relieving 
almost  instantly  agony  which  has  resisted  all  other  treatment.  This  ap- 
pears also  true  whether  valvular  disease  or  merely  functional  disorder 
exists.  Foster18  has  found  the  drug  of  great  service  in  aortic  insuf- 
ficiency with  excessive  hypertrophy  and  severe  frontal  headache. 

The  violent  cardiac  action  which  is  produced  by  the  inhalation  of 
the  nitrite  has  led  to  its  employment  as  a  cardiac  stimulant,  and  it  has 
been  much  commended  by  various  clinicians  in  all  forms  of  sudden  heart- 
failure^  even  when  such  failure  is  dependent  upon  fatty  degeneration  or 
other  disease  of  the  heart  itself.  The  direct  stimulant  influence,  if  it  exist 
at  all,  of  amyl  nitrite  upon  the  heart  is,  however,  of  the  briefest  duration, 
and  if  the  least  overdose  of  the  drug  be  given,  passes  into  cardiac  de- 
pression. The  zone  between  stimulation  and  depression  of  the  heart  by 
the  nitrite  is  so  narrow  that  the  greatest  care  must  be  exercised  whenever 
there  is  any  cardiac  disease,  or  whenever  the  heart  is  violently  depressed  by 
such  a  poison  as  chloroform.  Although  Reichert  states  that  he  has  seen 
the  blood -pressure  and  pulse-wave,  which  had  been  depressed  almost  to 
zero  by  ethylene  bichloride,  greatly  increased  by  amyl  nitrite,  in  an  elabo- 
rate series  of  experiments  made  by  H.  C.  Wood  with  chloroform  no  such 
effect  could  be  obtained,  and  in  recorded  cases  of  cardiac  failure  in  anaes- 
thesia the  amyl  salt  has  failed.  Its  use  should  always  be  tentative. 

Its  physiological  action  would  indicate  that  it  should  be  of  service  in 
all  cases  of  spasm  of  the  capillaries,  of  the  bronchial  tubes,  and  of  the 
muscular  system  generally.  Accordingly,  Oscar  Berger  19  and  others 
have  used  it  with  very  good  effect  in  migraine  with  capillary  contraction. 

Amyl  nitrite  is  of  very  great  value  for  the  purpose  of  relaxing  spasms ; 
it  will  usually  abort  a  paroxysm  of  asthma,  but  in  practice  it  will  be 
found  that  the  asthmatic  patient  becomes  so  rapidly  accustomed  to  the 
use  of  the  drug  as  to  make  it  of  comparatively  little  value.  In  a  fully 
formed  paroxysm  of  epilepsy  it  must  be  used  with  caution,  because  the  pa- 
tient's condition  will  obscure  its  early  effects  ;  but  in  the  status  epilepticus, 
when  there  is  an  almost  indefinite  repetition  of  the  fits,  the  remedy  may 
be  of  great  use  in  stopping  the  convulsions.  When  there  is  a  notable  in- 


DEPRESSO-MOTORS.  259 

terval  in  ordinary  epilepsy  between  the  aura  and  the  convulsion,  the  latter 
can  usually,  if  not  always,  be  entirely  prevented  :  the  patient  should  carry 
a  small  vial  containing  a  few  drops  of  the  drug  or  so-called  ' '  pearls' ' 
(minute  flasks,  each  containing  five  minims,  which  are  to  be  broken  in  a 
handkerchief),  and  should  inhale  the  amyl  salt  so  soon  as  the  aura  is  felt. 

S.  Weir  Mitchell 20  calls  attention  to  the  value  of  the  nitrite  as  an  aid 
in  diagnosing  those  occasional  cases  of  nervous  disorder  in  which  petit 
mal  is  simulated  by  attacks  really  due  to  passing  congestion  of  the  nerve- 
centres.  He  asserts  that  in  these  cases  amyl  nitrite  instead  of  arresting 
the  paroxysm  increases  its  severity. 

In  nervous  spasmodic  dysmenorrhcea,  it  is  stated  by  various  authorities 
that  inhalation  of  amyl  nitrite  will  sometimes  bring  immediate  relief,  two 
to  six  drops  being  given  when  the  pain  comes  on,  and  repeated  pro  re 
nata.  As' was  first  pointed  out  by  William  F.  Jenks,21  the  nitrite  is  most 
effective  in  arresting  puerperal  convulsions,  but  if  the  convulsions  occur 
shortly  after  parturition  the  use  of  the  nitrite  is  attended  by  the  greatest 
danger  of  producing  uterine  relaxation  and  serious  or  even  fatal  post- 
partum  hemorrhage. 

Amyl  nitrite  is  a  very  valuable  remedy  in  the  treatment  of  tetanus  and 
of  strychnine -poisoning.  In  the  experiments  of  St.  Clair  Gray,22  which 
have  been  substantially  confirmed  by  Hobart  A.  Hare,23  although  one- 
quarter  of  a  grain  of  strychnine  was  found  to  be  sufficient  to  cause  death 
in  an  immediate  convulsion  in  the  rabbit,  no  decided  symptoms  whatever 
were  induced  in  two  rabbits  by  the  subcutaneous  injection  into  each  of 
half  a  grain  of  strychnine  with  ten  drops  of  the  nitrite.  During  a  par- 
oxysm of  cramp  asphyxia  from  strychnine,  the  poison  of  tetanus,  or  other 
similarly  acting  cause,  the  nitrite  should  be  given  hypodermically,  the 
lack  of  respiratory  movement  interfering  with  its  absorption  through  the 
lungs. 

TOXICOLOGY. — We  know  of  no  deaths  recorded  from  amyl  nitrite, 
though  very  alarming  symptoms  have  resulted  in  various  cases.  Ten 
minims  of  a  ten  per  cent,  solution,  hypodermically  injected,  are  said  to 
have  been  followed  by  two  successive  furious  epileptic  convulsions,  each 
preceded  by  arrest  of  respiration  and  of  the  heart's  action,  to  which 
arrest  they  were  probably  due.  *  Three  drachms  caused  no  other  symp- 
toms than  violent  vomiting.  One  drachm  occasioned  great  weakness,  cya- 
nosis, and  very  feeble,  slow,  intermittent  pulse.  Two  drachms  caused 
vomiting  within  five  minutes,  great  weakness  of  the  pulse,  slow  respiration, 
temperature  below  95°  F. ,  semi-coma,  with  haemoglobin,  but  no  sugar 
or  blood-corpuscles,  in  the  urine  for  twelve  hours  ,after  the  poisoning. 

The  best  treatment  for  the  poisoning  would  consist  in  favoring  vomit- 
ing by  apomorphine  or  other  agents,  and  the  use  of  artificial  respiration 
and  hypodermic  injections  of  strychnine  and  digitalis.  That  there  is 

*  Strahan  (Journ.  Ment.  Set.,  xxx.  252),  J.  Roesen  (Centralb.f.  Klin.  Med.,  1888), 
George  E.  Shoemaker  (Med.  News,  1893,  i.),  and  Stansfield  (Brit.  Med.  Journ.). 


260  GENERAL  REMEDIES. 

between  the  latter  drug  and  a  nitrite,  so  far  as  the  circulation  is  con- 
cerned, direct  antagonism  has  been  shown  by  C.  R.  Marshall,"  who 
found  that,  in  accordance  with  the  doses  used,  the  vaso-dilator  influence 
of  the  nitrite  would  put  an  end  to  the  high  pressure  caused  by  digitalis,  or 
that  digitalis  would  elevate  the  lower  blood-pressure  of  the  nitrites,  or  that 
the  two  drugs  would  just  counteract  each  other,  and  that  digitalin  would 
overcome  the  diastolic  cardiac  arrest  produced  by  the  nitrite,  or  the 
nitrite,  if  in  excess,  would  overcome  the  systolic  arrest  of  the  frog's 
heart  produced  by  digitalin. 

ADMINISTRATION. — As  already  stated,  the  method  of  administration 
usually  employed  hitherto  is  inhalation,  from  one  to  three  or  five  drops 
being  placed  on  a  handkerchief  and  held  near  the  mouth  or  nose,  the 
handkerchief  being  removed  so  soon  as  a  sense  of  fulness  of  the  head 
is  experienced.  We  have  given  it  by  the  mouth,  dropped  upon  a  lump 
of  sugar  and  taken  instantly  in  doses  of  two  or  three  drops.  There  is 
not  at  present  sufficient  evidence  to  enable  us  to  decide  as  to  the  maxi- 
mum amount  of  the  drug  which  it  is  safe  to  give.  In  a  case  of  cholera, 
D.  B.  Smith 25  exhibited  hypodermically  two  drachms  in  the  course  of  an 
hour  and  thirty-six  minutes  without  inducing  any  serious  symptoms,  and 
a  dose  of  a  dessertspoonful  has  been  recovered  from,26  emetics  being 
given.  Used  with  care,  the  nitrite,  although  a  very  rapidly  acting  and 
powerful  agent,  seems  to  be  safe,  since  we  have  never  seen  either  in  man 
or  in  the  lower  animals  any  sudden  or  unexpected  action, — any  influence 
out  of  proportion  to  the  amount  given.  It  must  be  borne  in  mind  that 
the  symptoms  generally  increase  in  intensity  for  a  minute  or  two  after 
the  withdrawal  of  the  drug  from  inhalation. 

ETHYL  NITRITE. — It  is  not  to  be  doubted  that  all  of  the  nitrites  de- 
pend for  their  physiological  activity  on  their  acid-radical,  and  that  most 
of  them  have  similar  physiological  properties.  This  has  been  shown  to 
be  true  of  ethyl  nitrite  (Richardson1  and  Leech2).  Leech  asserts  that 
the  ethyl  nitrite  has  the  great  advantage  over  the  amyl  salt  of  greater  per- 
manency of  action,  the  effect  of  the  single  dose  lasting  from  a  half  to  two 
hours.  He  highly  commends  in  asthmatic  bronchitis  a  solution,  which 
he  states  to  be  stable,  composed  of  three  parts  of  ethyl  nitrite,  five  of 
glycerin,  and  ninety-two  of  absolute  alcohol  ;  dose,  thirty  to  ninety 
minims  (2-6  C.c. ). 

SODIUM  NITRIS.  U.  S. — It  has  been  demonstrated  by  E.  T.  Reichert l 
that  the  general  physiological  action  of  sodium  and  of  potassium  nitrite 
is  indistinguishable  from  that  of  amyl  nitrite,  except  in  being  much  less 
rapid  and  more  permanent.  (See  also  G.  A.  Atkinson.2)  Doses  of 
six  to  ten  grains  in  man  sufficed  to  raise  the  pulse  to  no  or  120,  with 
flushing  of  the  face  and  intra-cranial  throbbing ;  the  symptoms  usually 
began  in  twenty  minutes  and  lasted  several  hours,  and  were  in  no  case 
disagreeably  severe.  Eructations  of  a  phosphorus-like  taste  were  nearly 


DEPRESSO-MOTORS.  261 

always  present.  Ten  to  fifteen  grains  have  produced  complete  muscular 
relaxation,  livid  lips,  headache,  etc.,  lasting  three  hours.  Twenty  grains 
of  the  commercial  sodium  nitrite  have  been  given  without  serious  effect, 
but  of  a  pure  article,  either  of  the  sodium  or  the  potassium  nitrite,  the 
dose  is  three  grains  (o.  2  Gm. ) ;  five  grains  have  produced  serious  symp- 
toms.3 The  dose  may  be  repeated  every  two  hours,  cautiously. 

SPIRITUS  GLYCERYLIS  NITRATIS.  U.  S.  — Spirit  of  Glonoin,  a  one  per 
cent,  alcoholic  solution  of  glonoin  trinitrate  or  nitroglycerin,  is  a  clear, 
colorless  liquid,  having  the  odor  and  taste  of  alcohol.  As  very  minute 
quantities  are  capable  of  producing  violent  symptoms,  great  care  should 
be  exercised  in  tasting  it  or  in  applying  it  to  the  skin.  Moreover,  if  any 
considerable  quantity  of  it  be  spilled,  the  evaporation  of  the  alcohol  is 
liable  to  be  followed  by  a  dangerous  explosion.  Full  therapeutic  doses 
of  the  spirit  of  glonoin  cause  in  man  giddiness,  constriction,  or  other 
abnormal  sensations  in  the  head,  often  amounting  to  severe  headache, 
choking  in  the  throat,  sometimes  nausea,  and  rapid  cardiac  action,  with 
lessened  arterial  pressure.  After  toxic  doses  there  is  great  failure  of  the 
heart's  action.  A  single  drop  is  said  to  have  caused  insensibility,  and 
in  the  case  of  Mr.  Field,1  who  took  two  drops,  loss  of  consciousness  and 
of  the  pulse  at  the  wrist  was  complete.  J.  Noer 2  attributed  the  follow- 
ing symptoms  in  a  woman  to  the  use  of  ten-drop  doses  of  the  alcoholic 
solution  of  nitroglycerin.  The  pulse  was  slow,  intermittent,  and  very 
irregular,  the  pupils  dilated,  the  urine  scanty  and  containing  considerable 
pigment.  There  were  also  pain  in  the  region  of  the  heart,  intense  head- 
ache, sense  of  constriction  around  the  forehead,  and  great  weakness  of 
the  muscles.  Lauder  Brunton  and  Tait3  have  found  that  upon  blood- 
coloration,  arterial  pressure,  nerve-centres,  and  muscles  nitroglycerin  acts 
very  much  as  does  amyl  nitrite.  This  similarity  of  action  between  nitro- 
glycerin and  the  nitrites  has  been  confirmed  by  Murrell  and  Matthew 
Hay,4  also  by  A.  Henocque,5  and  is  remarkable,  as  nitroglycerin  may 
be  regarded  as  glyceryl  nitrate.  It  has  been  shown,  however,  by  Hay, 
that  during  its  alkaline  decomposition  it  yields  nascent  nitrous  acid,  and 
it  can  scarcely  be  questioned  that  this  acid  is  developed  in  the  blood  and 
acts  upon  the  system.  Amblyopia  is  said  to  have  resulted  from  prolonged 
exposure  to  the  fumes  of  nitroglycerin  (Hogg7). 

The  effect  of  nitroglycerin  is  certainly  more  prolonged  than  is  that  of 
amyl  nitrite.  The  statement  of  Korczynski,6  that  the  maximum  effect  of 
a  dose  in  man  is  reached  in  from  three  to  five  minutes,  whilst  the  influ- 
ence is  dispersed  in  three-quarters  of  an  hour,  is  as  accurate  as  can  be 
made.  Nitroglycerin  has  come  into  great  favor  for  all  conditions  in 
which  amyl  nitrite  has  been  employed.  In  angina  pectoris,  in  cardiac 
failure,  in  asthma,  in  ur&mia,  and  in  puerperal  eclampsia  it  may  be  sub- 
stituted for  amyl  nitrite  with  advantage  whenever  any  persistency  of  action 
is  desired.  It  is  also  very  largely  used  in  cases  of  habitual  high  arterial 
pressure,  especially  in  arterial  fibrosis  in  which  the  increased  peripheral 


262  GENERAL  REMEDIES. 

resistance  is  developing  or  has  produced  increased  cardiac  power.  Even 
its  action  is,  however,  too  fugacious  to  be  of  much  service  in  these  cases, 
and  it  should  be  administered  every  hour  when  a  decisive  effect  is  wanted. 
In  some  cases  of  acute  apoplexy  with  high  arterial  pressure  it  might  be  of 
great  service.  The  dose  is  one  to  two  minims  (0.06-0. 12  C.c. ). 

Erythrol  Tetranitrate. — A  crystalline  solid  which,  when  pure,  is  colorless,  but 
which  is  prone  to  decomposition  and  to  become  yellow.  It  is  a  violent  explosive 
whose  trituration  has  caused  death.  It  is  slightly  soluble  in  water,  but  readily  in 
alcohol.  Its  physiological  action  appears  to  be  entirely  parallel  to  that  of  glonoin, 
excepting  in  that  its  influence  is  less  powerful  and  is  much  more  prolonged.  In  man 
its  effects  are  said  not  to  be  apparent  in  less  than  half  an  hour  and  to  last  for  more 
than  an  hour.  It  has  been  especially  recommended  in  the  treatment  of  angina 
pectoris.  As  its  alcoholic  solution  is  explosive,  it  should  always  be  used  in  tablets, 
whose  preparation  requires  great  care.  Dose,  from  one-half  to  one  grain  (0.03- 
0.064  Gm.). 

LOBELIA.     U.  S. 

The  leaves  and  tops  of  the  indigenous  herb  Lobelia  inflata.  The 
dried  plant  has  a  slight  irritating  odor  and  a  taste  at  first  scarcely  per- 
ceptible, afterwards  burning,  acrid,  and  attended  by  a  flow  of  saliva. 
Proctor  discovered  the  alkaloid  lobeline,  which  was  long  believed  to  be 
liquid,  until  J.  U.  and  G.  G.  Lloyd  obtained  it  in  broad,  colorless,  odor- 
less, and  tasteless  crystals.* 

PHYSIOLOGICAL  ACTION. — The  symptoms  produced  by  large  doses 
of  lobelia  in  man  are  nausea,  soon  followed  by  violent  vomiting,  accom- 
panied by  intense  prostration,  as  is  shown  by  feeble  pulse,  cold  sweats, 
pale  skin,  and  great  muscular  relaxation.  Purging  may  or  may  not 
occur.  Numerous  cases  of  fatal  poisoning  by  it  have  been  recorded. 
The  symptoms  are  those  above  mentioned,  intensified  ;  in  some  cases 
vomiting  does  not  occur,  and  it  is  especially  under  these  circumstances 
that  fatal  effects  have  been  noted.  Burning  in  the  fauces  and  oesophagus, 
and  epigastric  distress,  in  addition  to  the  intense  prostration,  bordering 
upon  collapse  and  finally  merging  into  complete  collapse,  with  coma, 
stupor,  muscular  tremblings,  and  in  some  cases  convulsions,  precede  the 
fatal  termination. 

In  mammals  the  symptoms  produced  by  lobelia  are  :  slowing  and  irregularity 
of  the  respiration  ;  progressive  failure  of  the  muscular  power  ;  violent  vomiting  in 
those  animals  which  have  the  power  of  vomiting  ;  dilated,  fixed  pupil ;  convulsive 
seizures ;  fall  of  the  bodily  temperature,  and  death  from  asphyxia,  the  heart  con- 
tinuing to  beat  after  the  failure  of  respiration,  the  dominant  physiological  action  of 
the  drug  being  its  influence  upon  the  respiratory  centres.  When  given  to  the  frog, 
lobeline  produced  failure  of  voluntary  movement,  with  distinct  loss  of  coordination 
and  disturbances  of  respiration.  Unless  the  dose  has  been  too  large,  there  is  pri- 
mary increase  of  the  reflex  activity,  which,  however,  sinks  below  the  normal  until 
it  is  lost. 

*  The  Messrs.  Lloyd  also  assert  that  there  is  a  second  alkaloid  in  lobelia,  but  the 
researches  of  Dreser1  render  it  probable  that  this  second  alkaloid  is  a  derivative  from 
lobelime. 


DEPRESSO-MOTORS.  263 

All  experimenters  seem  to  be  in  accord  in  concluding  that  the  final 
paralysis  caused  by  lobelia  is  due  to  a  direct  paralyzing  action  upon  the 
motor  nerves.  Berstein  called  attention  to  the  fact  that  the  spinal  cord 
of  the  frog  is  usually  supplied  with  blood  from  the  anterior  spinal  artery, 
and  that  by  thorough  and  complete  section  of  the  cord  the  lower  segment 
is  cut  off  from  the  general  circulation.  Experimenting  in  accordance 
with  this,  Dreser J  found  that  the  increased  reflex  activity  produced  by 
lobelia  was  confined  to  the  anterior  section  of  the  cord  and  tributary 
muscles,  and  concludes  that  lobeline  is  a  direct  spinal  stimulant. 

Respiration. — The  researches  of  Dreser  seem  to  show  that  both  the 
respiratory  centre  and  the  vomiting  centre  in  the  medulla  oblongata  are 
primarily  excited  by  lobeline  ;  hence  the  vomiting,  and  hence,  also,  the 
increase  not  only  in  the  rate  of  the  respiration,  but  in  the  amount  of  air 
taken  in  and  out  from  the  lungs,  as  observed  by  Dreser.  This  condition 
of  excitement  is  followed  by  paralysis  of  the  respiration,  which  after  very 
large  doses  may  come  on  abruptly,  even  within  two  or  three  minutes  after 
the  injection  of  the  poison.  According  to  Dreser,  the  paralysis  of  the 
motor  nerves,  noted  in  the  frog,  is  of  little  importance  in  the  mammal, 
the  respiratory  centre  being  so  susceptible  to  the  drug  that  it  is  paralyzed 
before  the  nerves.  Dreser  also  found  that  there  is  a  peripheral  palsy  of 
those  vagus  filaments  which  have  influence  upon  the  bronchial  muscles. 

Circulation. — According  to  Ott2  and  Afanasieff,3  lobelia  produces  a 
rise  of  the  arterial  pressure,  which  in  Ott's  experiments  was  not  prevented 
by  previous  high-up  section  of  the  spinal  cord,  and  must,  therefore,  be 
due  to  an  action  either  of  the  heart  or  of  the  muscles  in  the  arterial  walls. 
Because  he  found  that  no  rise  of  pressure  is  produced  by  lobelia  in  the 
nicotinized  rabbit,  Ott  concludes  that  the  alkaloid  is  a  stimulant  to  the 
arterial  walls.  On  the  other  hand,  in  the  experiments  of  Afanasieff, 
lobeline  caused  in  the  frog's  heart  a  period  of  increased  work,  followed, 
if  the  dose  were  large  enough,  by  loss  of  power  ending  in  diastolic  arrest. 
In  the  later  stages  of  lobeline-poisoning  the  arterial  pressure  falls  progres- 
sively, so  that  it  is  probable  that  lobelia  first  stimulates  and  afterwards 
paralyzes  both  the  heart  and  the  arteries.  A  very  important  point  to  be 
noted  is  that  the  action  of  lobelia  upon  the  circulation  is  entirely  subordi- 
nate to  its  influence  upon  the  nerve-centres,  especially  upon  respiration, 
and  is,  therefore,  of  no  value  to  the  therapeutist. 

TOXICOLOGY. — The  symptoms  of  lobelia-poisoning  have  been  suffi- 
ciently described.  The  treatment  should  consist  in  washing  out  the 
stomach  with  plenteous  draughts  of  a  warm  solution  of  tannic  acid,  in 
the  free  exhibition  of  opium,  alcohol,  ammonia,  strychnine,  and  digitalis, 
and  in  the  use  of  external  stimulation  by  dry  heat,  frictions,  mustard,  etc. , 
precisely  as  in  poisoning  from  veratrum  viride. 

THERAPEUTICS. — The  former  use  of  lobelia  as  an  emetic,  and  for  the 
purpose  of  relaxing  spasm  in  various  diseases,  has  been  entirely  super- 
seded by  more  effective  and  less  dangerous  remedies.  Lobelia  remains, 
however,  a  valuable  drug  in  the  treatment  of  asthma,  or  acute  bronchitis 


264  GENERAL  REMEDIES. 

with  bronchial  spasm,  in  which  it  may  be  given  in  small  repeated  doses  at 
long  intervals,  or  in  severe  attacks  every  few  minutes  until  nausea  is 
induced.  An  infusion  (one  ounce  to  a  pint)  has  been  strongly  recom- 
mended as  a  local  application  in  the  eczema  produced  by  the  Rhris  toxi- 
codendron,  or  "poison-vine. ' '  The  dose  of  the  tincture  (TINCTURA  LOBE- 
LI^E — ten  per  cent.,  U.  S. ),  as  an  expectorant,  is  twenty  to  forty  minims 
(0.6—1.2  C.c. )  ;  in  the  paroxysm  of  asthma,  one-half  to  one  fluidrachm 
(2-4  C.c.)  every  half-hour  until  nausea  is  induced.  That  of  the  fluid 
extract  (FLUIDEXTRACTUM  LOBELIA,  U.  S. )  is,  as  an  expectorant, 
one  to  five  minims.  According  to  S.  Nunes,4  from  five  to  forty  centi- 
grammes of  lobeline  may  be  given  a  day,  but  in  any  case  the  first  dose 
should  not  exceed  one-fortieth  of  a  grain,  to  be  increased  pro  re  nata. 


GELSEMIUM.     U.  S. 

The  root  of  Gelsemium  sempervirens,  \hzyellow  or  Carolina  jessamine, 
a  beautiful  climbing  plant  of  the  Atlantic  Southern  United  States,  distin- 
guished by  its  large,  axillary,  very  fragrant,  clustered  blossoms  and 
perennial  dark  green  leaves.  The  very  light,  fibrous,  dirty  yellowish 
root  has  a  bitterish  taste,  and  contains  an  alkaloid,  Gelsemine,  in  combi- 
nation with  Gelseminic  Acid,  both  discovered  by  Wormley. 

PHYSIOLOGICAL  ACTION. — Absorption. — The  alkaloid  gelsemium  is 
rapidly  absorbed  and  is  eliminated  unchanged  by  the  kidneys. 

General  Action. — There  is  a  wide  range  of  susceptibility  in  man  to  the 
influence  of  gelsemium,  some  individuals  being  profoundly  influenced  by 
a  dose  which  has  no  perceptible  effect  upon  another  person.  After  the 
smallest  active  dose  (five  to  fifteen  minims  of  the  fluid  extract),  the  only 
symptom  is  languor  ;  with  it  may  be  a  little  lowering  of  the  force  and 
frequency  of  the  pulse.  When  a  somewhat  larger  amount  is  ingested,  to 
the  languor  are  added  dizziness  and  disturbance  of  vision,  with,  in  some 
cases,  a  pain  over  the  brows.  Ringer  and  Murrell *  state  that  the  pupil 
is  contracted,  but  this  is  probably  an  inconstant  result.  After  toxic  doses 
of  the  poison  the  muscular  weakness  is  extreme,  and  in  several  cases 2  the 
flexors  of  the  arms  have  been  especially  affected.  The  disturbance  of 
sight  is  now  very  marked  ;  double  vision,  or  partial  or  even  complete 
blindness,  may  exist  ;  the  pupil  is  widely  dilated  and  immovable  ;  the 
external  rectus  muscle  is  weakened,  sometimes  sufficiently  to  produce  a 
marked  internal  squint  ;  the  eyelid  droops,  and  is  raised  with  difficulty 
or  falls  in  paralytic  ptosis.  If  the  patient  is  able  to  walk  at  all,  the  gait 
is  staggering  ;  the  jaw  drops,  articulation  fails  ;  the  general  sensibility  is 
much  impaired  ;  the  respiration  slow  and  labored  ;  the  pulse  feeble  and 
thready  ;  the  skin  bathed  in  a  cold  sweat ;  the  bodily  temperature  greatly 
lowered.  Sometimes  drowsiness  is  felt  after  moderate  doses  of  the  poi- 
son, but  consciousness  may  be  preserved  in  the  midst  of  very  severe 
symptoms,  although  in  all  the  fatal  cases  whose  record  we  have  met 
with  it  has  been  lost  before  death.  The  drug  acts  very  promptly,  symp- 


DEPRESSO-MOTORS.  265 

toms  usually  appearing  in  about  twenty  minutes  after  its  ingestion,  and 
beginning  to  subside  in  two  or  three  hours. 

Gelsemium  produces  in  the  lower  animals  symptoms  similar  to  those 
which  it  causes  in  man,  with  the  exception  that  convulsions  are  very 
generally  developed. 

The  convulsions  are  not  always  present,  but  they  have  been  observed  in  the 
frog,  pigeon,  cat,  rabbit,  and  dog.  The  loss  of  voluntary  power  precedes  the  con- 
vulsions, and  in  the  careful  experiments  of  Ringer  and  Murrell  upon  frogs  it  was 
found  that  the  cord  was  rapidly  exhausted  by  repeated  irritations,  so  that  convul- 
sions could  not  at  once  be  induced.  Bartholow  states  that  in  the  rabbit,  cat,  and 
pigeon  the  convulsive  movements  are  backward,  sometimes  amounting  to  complete 
somersaults. 

Nervous  and  Muscular  Systems. — Cerebrum. — The  retention  of  con- 
sciousness until  very  late  in  the  poisoning,  both  in  man  and  in  the  lower 
animals,  shows  that  the  drug  has  very  little  power  over  the  higher  cerebrum, 
although  the  drowsiness  and  the  final  loss  of  consciousness  prove  that  it  is 
not  entirely  devoid  of  such  influence.  The  convulsions  are  not  cerebral, 
as  is  proved  by  their  occurrence  in  the  pithed  frog  (Ringer  and  Murrell), 
and  below  the  point  of  section  in  mammals  with  divided  spinal  cord 
(Taylor8). 

Both  the  convulsions  and  the  paralysis  in  poisoning  by  gelsemine  are 
spinal.  Their  development  is  not  affected  by  tying  an  artery  before  poi- 
soning, so  as  to  protect  a  limb  (Bartholow,4  Ringer  and  Murrell5)  ;  more- 
over, the  afferent  and  motor  nerves  and  muscles  preserve  their  functional 
activity  until  death.*  The  convulsive  stage  of  gelsemine-poisoning  is 
preceded  by  exaggerated  reflex  activity  (I.  Ott6),  so  that  gelsemine  ap- 
pears to  cause  spinal  motor  excitation  followed  by  spinal  motor  paralysis. 

The  most  plausible  explanation  of  these  phenomena  is  (in  accordance  with  the 
doctrine  of  spinal  inhibition,  see  page  172)  that  gelsemine  is  a  depressant  and, 
finally,  paralyzant  to  both  the  spinal  inhibitory  ganglia-cells  and  to  the  spinal  motor 
nerve-cells,  but  attacks  primarily  inhibition  ;  so  that  in  the  first  stage  of  its  poison- 
ing excessive  motor  activity  results  from  the  paralysis  of  spinal  inhibition,  whilst  in 
the  final  stage  there  is  a  true  motor  paralysis  due  to  a  direct  paralysis  of  the  motor 
nerve-cells.  Ringer  and  Murrell,  however,  conceive  that  there  are  in  gelsemium 
two  active,  antagonistic  substances,  one  a  tetanizant,t  the  other  a  paralyzant ;  but 
in  their  own  experiments,  and  in  those  of  Ott,  gelsemine  believed  to  be  pure 
produced  convulsions.  Ott,  however,  found  gelsemic  acid  so  much  more  pow- 
erful in  its  convulsive  action  than  the  alkaloid  as  to  suggest  the  correctness  of 
Ringer  and  Murrell's  hypothesis. 

*  Ott,  Bartholow,  Ringer  and  Murrel.  (For  details,  see  eighth  edition  of  this 
treatise.) 

fin  confirmation  of  this,  A.  R.  Cushny  {Arch,  fur  Exper.  Pathol.,  1892,  xxxi.) 
finds  that  there  are  two  bases  in  gelsemium,  to  one  of  which  he  gives  the  namegelse- 
min,  the  other  gelseminin.  Gelsemin,  he  finds,  produces  in  the  frog  violent  spinal  ex- 
citement with  increase  of  the  reflexes,  followed  by  paralysis  due  to  an  action  upon  the 
nerve-endings.  Gelseminin  is  the  more  active  of  the  two,  producing  a  paralysis  by  direct 
action  upon  the  spinal  centres  and  having  also  a  curare-like  paralytic  influence  upon  the 
nerve- trunks. 


266  GENERAL  REMEDIES. 

Dr.  Bartholow  says  that  ' '  it  [gelsemium]  acts  also  on  the  sensory 
portion  of  the  cord,  producing  at  last  complete  anaesthesia  ;  but  this 
effect  in  warm-blooded  animals  and  in  man  is  toxic  only,  and  follows  the 
paralysis  of  the  motor  functions."  This  may  be  correct,  but,  so  far  as 
we  know,  has  not  been  experimentally  proved. 

Respiration. — Gelsemium  usually  kills  by  a  paralysis  of  respiration. 
According  to  the  researches  of  Burdon  Sanderson  and  of  Ringer  and 
Murrell,  immediately  after  the  ingestion  the  extent  of  the  respiration,  but 
not  its  rate,  is  increased  ;  very  shortly,  however,  both  rate  and  depth 
enter  a  condition  of  progressive  palsy  ending  in  death.  The  respiratory 
changes  are  the  product  of  a  direct  action  upon  the  respiratory  centres, 
being  uninfluenced  by  previous  section  of  the  vagi. 

Circulation. — The  action  of  moderate  doses  of  gelsemium  upon  the 
circulation  is  not  pronounced,  but  the  toxic  dose  depresses  both  the  pulse- 
rate  and  the  pressure.  As  this  occurs  after  previous  section  of  all  the 
cardiac  nerves  of  the  spinal  cord  (Ott7),  it  is  probable  that  the  poison 
exerts  a  direct  influence  upon  the  heart.  How  far  or  in  what  way  it 
affects  the  arterial  system  we  have  no  knowledge. 

Eye. — Ringer  and  Murrell  affirm  that  decided  non-toxic  doses  of  the 
drug  cause  contraction  of  the  pupil.  However  this  may  be,  marked  dila- 
tation of  the  pupil  is  a  very  constant  symptom  in  the  poisoning,  and  the 
local  application  of  gelsemine  to  the  eye  produces  violent  mydriasis,  with 
paralysis  of  accommodation. 

It  would  seem  probable  that  the  mydriasis  is  due  to  an  action  upon  the  periph- 
eral nerve-ending  in  the  eye.  The  palsy  of  the  external  rectus  and  the  ptosis  indi- 
cate that  such  action  is  paralytic,  so  that  it  is  a  probable  conclusion  that  peripheral 
oculo- motor  paralysis  is  the  cause  of  the  dilatation  of  the  pupil.  The  falling  of  the 
jaw  and  the  loss  of  the  power  of  articulation  indicate  that  all  the  motor  nerves  of 
the  head  are  acted  upon  by  the  poison. 

SUMMAHY. — The  characteristic  symptoms  of  gelsemium-poisoning 
are  progressive  muscular  "weakness,  double  vision,  dilated  pupils,  squint, 
ptosis,  and  dropping  of  the  jaw.  The  chief  physiological  action  of 
the  remedy  seems  to  be  depression  of  the  motor  spinal  cord,  including 
the  respiratory  centres ;  the  depression  apparently  being  preceded  by 
a  stage  of  stimulation.  The  effect  of  the  remedy  upon  the  circulation  is 
not  pronounced,  but  toxic  doses  depress  directly  the  heart  and  arterial 
pressure. 

THERAPEUTICS. — Gelsemium  was  originally  employed  as  an  arterial 
sedative  and  febrifuge  in  the  malarial  fevers  of  the  South,  and  subse- 
quently in  other  sthenic  fevers.  It  appears  in  some  way  to  depress  the 
bodily  temperature,  but  certainly  possesses  no  controlling  influence  over 
the  arterial  system  at  all  comparable  to  that  of  veratrum  viride  and 
aconite.  Bartholow  commends  it  highly  in  pneiimonia  and  pleuritis ; 
its  influence  for  good  in  these  disorders  would  seem,  however,  to  be 
chiefly  associated  with  its  power  of  lessening  the  rapidity  of  respiration 
and  increasing  the  tendency  to  perspiration.  It  does  not  appear  proba- 
ble that  any  advantage  to  be  derived  from  it  will  counterbalance  the  dan- 


DEPRESSO-MOTORS.  267 

gers  attending  its  employment  in  the  large  doses  required.  In  asthma, 
spasmodic  laryngitis,  whooping-cough,  and  nervous  cough,  in  which  it  is 
also  recommended  by  Bartholow,  its  employment  seems  more  plausible, 
as  in  these  cases  there  is  a  distinct  spasmodic  element.  The  testimony  to 
its  value  in  cases  of  trigeminal,  ovarian,  and  other  neuralgias  is  strong. 
How  it  does  good  in  these  disorders  is  as  obscure  as  is  the  nature  of  the 
neuralgias,  and  in  our  hands  it  has  usually  failed.  The  marked  effect  of 
the  drug  upon  the  facial  nerves  would  appear  to  indicate  its  employment 
in  facial  neuralgias,  and  especially  in  facial  spasmodic  affections.  In 
acute  mania  the  drug  may  be  employed  in  full  doses  as  a  calmative. 

TOXICOLOGY. — I.  Ott  has  collected  six  cases  of  fatal  poisoning,  a 
teaspoonful  of  the  fluid  extract  being  the  smallest  amount  that  has 
caused  death  in  the  adult.  Wormley  believes  that  his  chemical  examina- 
tions have  shown  that  in  one  fatal  case  the  fluid  extract  ingested  could 
not  have  contained  more  than  one-sixth  of  a  grain  of  the  alkaloid. 

The  treatment  of  gelsemium-poisoning  should  be  conducted  on  gen- 
eral principles.  Our  present  knowledge  does  not  indicate  that  morphine 
and  gelsemium  are  physiological  antagonists,  but  George  S.  Courtright 8 
asserts  that  they  have  such  relation,  and  details  a  case  in  which  recovery 
occurred  after  the  ingestion  of  from  one  to  two  teaspoonfuls  of  the  tinc- 
ture, one  and  one-half  grains  of  morphine  having  been  given  hypoder- 
mically  and  one  grain  by  the  mouth. 

ADMINISTRATION. — The  dose  of  the  fluid  extract  (FLUIDEXTRACTUM 
GELSEMII,  U.  S. )  is  five  minims  (0.3  C.c. )  every  two  hours  until  con- 
stitutional effects  are  produced  ;  of  the  tincture  (TiNCTURA  GELSEMII — 
ten  per  cent.,  U.  S. ),  fifteen  to  thirty  minims  (1-2  C.c.). 

TABACUM.  —  Tobacco  is  no  longer  recognized  by  the  United  States 
Pharmacopoeia,  and  is  not  at  present  used  in  practical  medicine.  We 
shall  here  discuss  it  very  summarily,  referring  the  reader  to  the  tenth 
edition  of  this  treatise  for  an  elaborate  study  of  its  physiological  action. 

Tobacco  depends  for  its  activity  upon  the  presence  of  an  alkaloid, 
nicotine,  a  poison  of  such  intensity  that  it  has  caused  death  in  three 
minutes.  The  fatal  dose  of  nicotine  has  not  been  made  out.  One-thirty- 
second  of  a  grain  will  cause  serious  symptoms  ;  one-seventh  of  a  grain 
has  been  recovered  from.  The  symptoms  produced  by  tobacco  in  those 
unaccustomed  to  its  use  are  horrible  nausea  and  vomiting,  giddiness, 
intense  malaise,  with  weakness,  followed,  if  the  dose  has  been  sufficient,  by 
burning  pain  in  the  stomach,  purging,  free  urination,  extreme  giddiness 
passing  into  delirium,  a  rapid,  running,  and  finally  imperceptible  pulse, 
cramps  in  the  limbs,  absolute  loss  of  muscular  strength,  a  cold,  clammy 
skin,  and  finally  complete  collapse,  terminating  in  death. 

In  the  lower  animals,  especially  in  the  frog,  to  the  symptoms  com- 
monly seen  in  man  are  added  violent  convulsions,  which  are  of  spinal 
origin  and  are  followed  after  a  time  by  paresis,  which  is  probably  also  in 
part  of  spinal  origin,  although  it  has  been  demonstrated  that  tobacco  is 


268  GENERAL  REMEDIES. 

a  powerful  depressant  to  the  motor  or  efferent  nerves ',  acting  primarily  upon 
their  peripheral  filaments.  The  afferent  or  sensory  nerves  are  much  less 
affected  than  the  motor,  but  are  probably  also  depressed.  The  sympa- 
thetic ganglia  are  first  stimulated  and  then  depressed  by  nicotine.  To 
these  actions  are  probably  due  the  increase  of  saliva  and  other  secretions 
caused  by  small  doses  and  the  lessening  of  gland  activity  produced  by 
large  doses.  Upon  the  voluntary  muscles  the  drug  has  no  action. 

Upon  the  circulation  nicotine  has  a  very  distinct  influence,  producing 
first  rise  and  afterwards  fall  of  pressure.  The  rise  of  pressure  is  certainly 
in  part  due  to  stimulation  of  the  cardiac  muscles  or  ganglia,  but  prob- 
ably is  also  in  part  the  outcome  of  peripheral  contraction  of  the  vessels  ; 
and  it  is  further  probable  that  the  final  paralysis  is  due  to  a  double 
depressing  influence  upon  the  heart  and  the  arterial  walls,  although  these 
points  have  not  been  distinctly  proved. 

Upon  the  pupil  nicotine  acts  as  a  myotic,  probably  paralyzing  the 
peripheral  ends  of  the  sympathetic,  and  almost  certainly  stimulating  the 
oculo-motor  nerves. 

The  only  use  now  made  of  tobacco  in  medicine  is  in  the  preparation 
of  ointments  for  painful  hemorrhoids,  and  in  the  form  of  a  strong  wash 
for  pruritus.  Its  free  external  use  is  always  accompanied  by  danger, 
and  has  caused  death. 

The  dose  of  tobacco  is  five  grains  (0.32  Gm.),  in  infusion. 

TOXICOLOGY. — A  large  number  of  deaths  have  resulted  from  the 
medicinal  use  of  tobacco,  Husemann J  stating  that  no  less  than  ten  fatal 
cases  have  been  caused  by  tobacco  enemata  alone.  Copland  '*  has  seen 
a  clyster  containing  half  a  drachm  produce  death.  Even  smoking  has 
caused  an  acute  fatal  poisoning.  Melsens  affirms  that  the  smoke  of  half 
an  ounce  of  strong  tobacco  contains  sufficient  nicotine  to  prove  fatal.* 
In  the  only  case  of  criminal  nicotine-poisoning  on  record,  an  unknown 
amount  of  the  alkaloid  was  forced  into  the  mouth  of  the  victim,  causing 
death  in  from  three  to  five  minutes.*  The  treatment  of  tobacco-poisoning 
consists  in  washing  out  the  stomach,  the  free  administration  of  ammonia 
and  alcohol,  the  hypodermic  use  of  moderate  amounts  of  strychnine,  and 
the  employment  of  such  external  measures  as  dry  heat,  rubbings,  etc. 
If  these  fail,  artificial  respiration  should  be  maintained.  The  excessive 
use  of  tobacco  produces  in  some  persons  serious  nervous  disturbance, 
such  as  insomnia,  irritability,  general  feebleness  ;  the  most  characteristic 
symptom  is  a  peculiar  irregularity  of  the  heart's  action,  often  accompa- 
nied by  distinct  intermissions.  Amaurosis  is  also  sometimes  present,  f 

*  For  a  number  of  cases,  see  Still£'s  Therapeutics,  ii.  374. 

t  The  diagnosis  of  tobacco  amblyopia  depends  upon  the  history  of  the  abuse  of  the 
drug,  the  failure  to  improve  with  optical  therapeutics,  and  the  presence  of  a  scotoma,  usu- 
ally oval  in  shape  and  negative  in  character,  particularly  pronounced  for  red  and  green, 
while  the  periphery  of  the  field  of  vision  remains  unaltered.  If,  in  addition,  there  is  a 
quadrant-shaped  patch  of  atrophic  pallor  in  the  nerve-head,  the  diagnosis  becomes  still 
more  certain.  Atrophy  of  the  nerve  may  result,  but  in  many  cases  there  is  no  structural 
change,  as  the  symptoms  may  go  off  in  a  few  hours  (De  Schweinitz's  Toxic  Amblyopia). 


DEPRESSO-MOTORS.  269 

Jonathan  Hutchinson  *  affirms  that  he  has  seen  this  amaurosis  recovered 
from  by  the  use  of  opium  and  champagne  without  the  abandonment  of 
the  habit  of  smoking.  We  have  seen  impotence  as  the  only  distinct 
symptom  of  chronic  tobacco-poisoning. 

CONIUM.     U.S. 

The  U.  S.  Pharmacopoeia  recognizes  only  the  full-grown  fruit,  gathered 
while  green,  of  Conium  maculatum.  The  plant  is  umbelliferous,  a  native 
of  Europe,  but  naturalized  in  the  United  States.  The  dried  leaves  have 
a  strong  heavy  odor,  increased  by  the  addition  of  an  alkali,  and  resem- 
bling somewhat  that  of  mice.  They  are  bi-  or  tripinnate,  and  very  much 
incised.  The  fruits  are  one  to  two  lines  long,  roundish-ovate,  striated, 
with  five  crenated  ribs  on  the  outer  sides  of  the  easily  separable  halves  ; 
the  odor  is  that  of  the  leaves.  The  active  principle  is  Conine,  a  yellow- 
ish, oily,  liquid  alkaloid,  highly  volatile,  of  a  strong  odor  similar  to  that 
of  the  urine  of  mice,  and  of  a  very  acrid  taste.  It  is  freely  soluble  in 
alcohol  and  in  ether,  and  slightly  so  in  water,  with  which  it  forms  a 
hydrate,  and  it  coagulates  albumin  ;  when  exposed  to  the  air  it  under- 
goes decomposition,  becoming  first  brown,  afterwards  resinous  ;  heat 
accelerates  the  change. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Upon  the  mucous  mem- 
branes conium  acts  as  an  intense  irritant.  In  a  concentrated  form  it  is 
probably  fatal  to  all  highly  organized  tissues,  Christison  having  proved 
this  to  be  true  in  regard  to  the  muscles  which  are  not  influenced  by  the 
alkaloid  taken  internally.  It  is  absorbed  with  great  rapidity,  and  escapes 
through  the  system  chiefly  if  not  solely  through  the  kidneys.  Zaleski 
and  Dragendorfl  have  found  it  abundant  in  the  urine  during  the  first 
twelve  hours  of  the  poisoning  ;  Prevost  has  seen  the  urine  of  poisoned  ani- 
mals cause  in  a  frog  the  characteristic  general  palsy,  and  in  a  doubtful 
case  of  poisoning  this  physiological  test  might  decide  the  diagnosis. 

General  Action. — Full  physiological  doses  of  conium  produce  in 
man  quietude,  languor,  and  muscular  weakness.  After  toxic  doses  the 
weakness  becomes  extreme,  forcing  the  patient  to  the  horizontal  position, 
or  causing  him  to  stagger  or  fall  from  weakness  of  the  legs  when  he  at- 
tempts to  walk.  This  weakness  has  in  some  cases  been  attended  by 
burning  in  the  mouth,  fauces,  or  stomach,  nausea,  vomiting,  and  with  a 
sense  of  pressure  or  even  with  severe  frontal  pain.  As  the  case  pro- 
gresses consciousness  is  preserved,  but  the  paralytic  symptoms  become 
everywhere  pronounced.  The  pupils  sooner  or  later  dilate  ;  *  amblyopia 
from  paralysis  of  accommodation,  diplopia  from  irregular  weakness  of 
the  ocular  muscles,  and  ptosis  are  almost  universally  present,  and  the 
voice  may  be  weakened  to  a  whisper  or  lost.  Sensibility  is  maintained 
to  the  end.  Free  salivation  or  free  sweating  sometimes  occurs. 

*  The  experiments  of  Poehlmann  (quoted  by  Husemann1)  show  that  very  grave 
symptoms  may  be  induced  and  yet  the  pupils  remain  natural ;  but  sooner  or  later  they 
probably  always  dilate. 


270  GENERAL  REMEDIES. 

The  circulatory  phenomena  are  very  subordinate  ;  though  the  pulse- 
rate  may  at  first  fall,  later  it  becomes  more  rapid.  Consciousness  is 
usually  preserved  until  the  last,  but  may  be  lost  in  asphyxial  coma  some 
minutes  before  death,  which  results  from  paralysis  of  respiration. 

We  have  met  with  accounts  of  but  four  fatal  cases  of  such  character.  In  one, 
that  of  the  mistress  of  Dr.  Hermann  Jahn,  killed  in  a  few  minutes  by  from  ten 
to  fifteen  drops  of  the  alkaloid  (quoted  by  Husemann),  violent  palpitation  of  the 
heart  is  said  to  have  been  a  prominent  symptom.  The  chief  symptom  in  the  second 
case  *  was  universal  paralysis,  with  total  failure  of  voluntary  movement  and  of  the 
voice  before  consciousness  was  lost.  Convulsive  movements  were  present  very 
late  in  the  case.  Sensation  appeared  not  to  be  lost  until  death  was  at  hand. 

The  third  case  3  was  that  of  a  medical  electrician,  suffering  from  blepharo-facial 
spasm,  who  took,  beginning  four  hours  after  the  last  of  a  previous  series  of  divided 
doses  of  a  fluid  extract  amounting  to  one  hundred  and  eighty  drops,  at  4.10,  4.40, 
and  5.15  P.M.  fifty  minims  (one  hundred  and  fifty  in  all)  of  "  Squibb' s  fluid  ex- 
tract." The  first  dose  produced  dizziness  and  muscular  relaxation;  the  second, 
great  muscular  weakness,  inability  to  stand,  and  thickening  of  speech,  without 
relief  of  the  spasm  ;  the  third,  immediately,  some  nausea,  and  tremors  about  the 
chest.  At  6.10  there  were  nausea,  intense  muscular  weakness,  partial  ptosis, 
diplopia,  and  great  difficulty  of  speech  ;  the  pulse  was  60.  Shortly  after  this  the 
man  became  unable  to  speak  or  to  swallow.  He  made  signs  for  electricity,  and,  on 
being  asked  whether  the  chemical  or  the  faradic  current,  indicated  the  latter,  and 
also  the  place  of  application  of  the  electrodes,  but  was  unable  to  hold  one  of  the 
latter.  Shortly  after  this,  on  being  raised  up,  he  dropped  dead.  A  fourth  case,  in 
which  a  child  five  years  old  died  of  asphyxia  preceded  by  coma  and  paralysis  as  the 
result  of  taking  a  drachm  of  chloroform-water  containing  five  grains  of  the  extract 
of  conium,  is  recorded.4 

In  mammals  conium  produces  symptoms  parallel  with  those  observed 
in  man,  and  it  probably  acts  similarly  upon  all  vertebrates. 

In  frogs  convulsions  are  rarely  if  ever  present ;  in  birds  they  are  occasionally 
so  ;  in  mammals  they  are  more  frequent, — thus,  Ihmsen  saw  them  in  twelve  out  of 
twenty-three  experiments  ;  they  are  chiefly  clonic,  but  tonic  spasms  do  occur  in  the 
hind  legs.  As  the  legs  are  usually  affected  before  the  arms  in  man,  so  in  quadru- 
peds the  hind  extremities  are  usually  paralyzed  first.  The  respiration  is  generally 
much  affected,  and  the  heart  continues  to  beat  after  its  cessation. 

Spinal  Cord. — The  exact  influence  of  conine  upon  the  spinal  cord 
cannot  yet  be  considered  absolutely  determined,  but  it  is  most  probable 
that  the  poison  has  a  feeble  depressant  action.  Verigo  5  asserts  that  it  is 
a  powerful  spinal  depressant,  and  Pelvette  and  Martin- Damourette6  say 
that  it  acts  as  an  excitant.  Lautenbach,  in  carefully  investigating  the 
subject,  failed  to  obtain,  under  any  circumstances,  evidences  of  excite- 
ment of  the  cord  ;  he  did  succeed  in  producing  loss  of  reflex  activity 
when  the  nerve  was  protected  by  tying  the  artery  in  the  limb,  but,  as  in 
all  but  two  of  fifty-two  experiments  the  reflexes  in  the  protected  limb  were 
not  greatly  reduced  until  just  before  death,  it  is  plain  that  any  action  upon 
the  spinal  cord  is  unimportant  and  dominated  by  the  more  powerful 
peripheral  influences  of  the  poison.* 

*  The  experimental  results  obtained  by  A.  D.  Davidson  and  D.  Dyce  Brown  (Med. 
Times  and  Gazette,  July,  1870),  which  have  been  cited  as  favoring  the  absurd  theory  of 


DEPRESSO-MOTORS.  271 

Nervous  System.  —  Cerebrum. — The  retention  of  consciousness  and  all 
the  mental  faculties  almost  up  to  death  in  conium-poisoning  shows  that 
the  drug  has  but  little  influence  upon  the  general  cerebral  cortex.  Ac- 
cording to  Lautenbach,7  the  convulsions  which  occur  in  the  lower  animals 
are,  however,  of  cerebral  origin,  since  after  division  of  the  cord  they  were 
confined  to  those  portions  of  the  body  situated  above  the  section.  They 
are  probably  asphyxial  or  of  other  secondary  character. 

Nerves. — In  1856  Kolliker 8  announced  that  the  paralysis  of  conine- 
poisoning  is  due  to  paralysis  of  the  efferent  or  motor  nerves,  a  conclusion 
which  has  since  been  abundantly  confirmed. 

Kolliker  demonstrated  that  in  the  poisoned  frog  immediately  after  death  the 
galvanic  current  applied  to  the  nerve  is  powerless  to  induce  contractions  ;  that  if  by 
tying  the  aorta  access  of  the  poison  be  cut  off  from  the  hind  legs,  there  is  a  stage  of 
the  poisoning  in  which  galvanic  stimulation  of  the  nerve  of  the  front  leg  fails  to 
affect  the  tributary  muscles,  although  it  does  produce  reflex  contractions  in  the  hind 
legs ;  proof  that  the  anterior  afferent  nerves  and  the  spinal  cord  still  retain  func- 
tional activity  after  this  activity  has  been  lost  in  efferent  nerves  reached  by  the 
poison.  These  experimental  results  have  been  confirmed  by  Funke,9  by  Guttmann,10 
and  by  Pelvette  and  Martin- Damourette.*  The  latter  observers  extended  the  series 
by  severing  in  a  frog  all  the  tissues  at  the  upper  part  of  the  thigh  except  the  nerve, 
and  found  that  when  a  batrachian  so  prepared  was  poisoned  with  conine,  after  the 
paralysis  was  complete  in  all  portions  of  the  body  to  which  the  poison  had  access, — 
after  stimulations  of  the  poisoned  nerves  were  powerless  to  excite  contraction  in 
the  tributary  muscles, — the  leg  which  had  been  protected  from  the  action  of  the 
conine  upon  it  responded  not  only  to  irritations  applied  to  its  nerve,  but  also  to 
stimuli  placed  upon  distant  portions  of  the  body.  These  same  observers  also  noted 
that  when  conine  and  strychnine  were  given  simultaneously  to  a  frog  from  one  of 
whose  sciatic  nerves  the  circulation  (i.e.,  direct  access  of  the  poison)  was  cut  off 
in  either  of  the  manners  spoken  of,  they  produced  by  their  conjoint  action  a  com- 
mingling of  paralysis  in  all  other  parts  of  the  body  with  violent  tetanic  spasms  in  the 
protected  leg, — a  commingling  explainable  only  on  the  supposition  that  the  conine 
paralyzed  all  the  motor  nerves  to  which  it  had  access  through  the  circulation.  These 
experiments  upon  the  frog  have  been  confirmed  by  B.  F.  Lautenbach,11  Verigo,  A. 
W.  Hofmann,  Prevost,  H.  Schultz,12  and  Fliess,"  whilst  Hayashi  and  Muto17  have 
shown  that,  although  the  nerves  of  purely  voluntary  motion  are  acted  upon  in  the 
mammal  by  conine,  the  phrenic  nerve,  at  least  in  the  rabbit,  is  even  more  suscep- 
tible to  its  influence. 

It  has  been  generally  believed  that  conine  does  not  affect  the  sensory 
nerves,  but  the  evidence  appears  to  show  that  this  is  not  correct ;  only  that 
the  action  upon  the  sensory  nerves  is  so  much  less  decided  than  that  upon 
the  motor  fibres  that  it  counts  very  little  in  the  general  influence  of  the 
drug. 

In  1875  Gubler1*  called  attention  to  the  local  influence  of  conium  in  benumb- 
ing the  cutaneous  sensibility,  and  Lautenbach  found  that  when  he  tied  the  abdomi- 

Harley  that  the  corpora  striata  are  especially  affected  by  the  drug,  evidently  depended 
upon  an  arterial  anomaly  said  to  be  common  in  the  leg  of  the  cat. 

*  M.  Tiryakan  (Compt.-Rend.,  Ixxxvi.  1344)  has  affirmed  that  absolutely  pure  conine 
does  not  affect  the  nerves,  but  M.  Prevost  (Arch.  Physiol.  Norm,  et  Path.,  1880,  vii.)  has 
shown  that  chemically  pure  conine  bromohydrate  has  this  action. 


272  GENERAL  REMEDIES. 

nal  aorta  and  left  axillary  artery  in  the  frog,  and  then  injected  a  dose  of  conine  into 
the  abdomen,  irritation  of  the  leg  whose  nerve  was  not  protected  from  the  poison 
failed  to  cause  reflex  movements  at  a  time  when  irritation  of  the  protected  nerves 
produced  reflex  actions  in  distant  parts  of  the  body. 

Muscles. — All  observers  agree  that  in  conium-poisoning  the  muscles 
themselves  are  not  affected. 

Pupil. — The  pupil  is  generally  dilated  by  conine  ;  but  both  Von 
Praag 15  and  Verigo  assert  that  the  phenomenon  is  not  constant,  at  least 
in  animals.  The  ptosis  of  conium-poisoning  indicates  that  the  dilatation 
of  the  pupil  is  due  to  oculo-motor  paralysis.  The  known  action  of  the 
drug  upon  nerve-trunks  indicates  that  this  paralysis  is  peripheral, — a  con- 
clusion corroborated  by  the  experiments  of  I.  Hoppe 16  and  of  Lautenbach, 
each  of  whom  found  that  when  conine  is  dropped  into  the  eye  of  an  ani- 
mal it  causes  at  first  contraction,  apparently  due  to  the  intense  irritation, 
and  afterwards  dilatation,  of  the  pupil. 

Temperature. — Verigo,  Von  Praag,  and  others  affirm  that  lethal 
doses  of  conium  cause  a  decided  lowering  of  temperature  ;  but  Lauten- 
bach asserts  that  the  drug  decidedly  increases  the  temperature  both  when 
in  therapeutic  and  when  in  toxic  doses. 

Circulation. — No  sufficient  investigation  has  as  yet  been  made  upon 
the  action  of  conine  upon  the  circulation.  Lautenbach  states  that  the 
arterial  pressure  falls  immediately  after  the  injection  of  conine,  and  after- 
wards rises  far  above  the  normal  point,  and  that  the  pulse  is  at  first 
accelerated,  but  afterwards  retarded.  The  secondary  rise  of  pressure 
is  probably  due  to  asphyxia.  The  primary  pulse-acceleration  is  ex- 
plained by  the  observation  of  Pel6nard  (confirmed  by  Prevost)  that  the 
pneumogastrics  are  paralyzed  before  the  motor  nerves.  Prevost  finds  that 
the  heart  itself  is  scarcely  affected  by  the  poison. 

SUMMARY. — The  chief  symptom  of  poisoning  by  conium  is  a  failure 
of  voluntary  and  involuntary  movement,  the  result  of  a  progressive 
paralysis  of  the  motor  nerves.  The  cerebrum  is  not  affected,  hence 
consciousness  is  preserved  to  the  last.  The  pupil  is  dilated  by  a  periph- 
eral paralysis  of  the  oculo-motor  nerve.  The  sensory  nerves  and  the 
spinal  cord  are  probably  feebly  depressed.  It  is  probable  that  the  alka- 
loid does  not  directly  act  upon  the  circulatory  apparatus  except  to 
paralyze  the  pneumogastrics. 

THERAPEUTICS. — The  paralytic  action  of  conium  naturally  suggests 
its  use  in  spasmodic  affections  ;  and  accordingly  it  has  been  tried  in 
chorea,  in  paralysis  agitans,  in  whooping-cough,  and  in  other  diseases  of 
similar  nature.  Although  it  seems  not  to  have  met  with  continued 
favor,  and  is  but  little  used,  it  may  be  employed  when  life  is  threatened 
by  the  mere  convulsive  actions,  which  it  will  sometimes  temporarily  sus- 
pend. In  maniacal  and  hysterical  excitement,  the  drug  in  full  doses  is 
said  to  produce  a  highly  favorable  condition  of  calm  and  relaxation  ;  and 
in  the  treatment  of  the  insane,  conium  is  much  used  by  some  alienists. 


DEPRESSO-MOTORS. 


273 


Conium  was  formerly  employed  to  relieve  pain  or  as  a  deobstruent 
and  alterative  in  chronic  glandular  or  arthritic  diseases,  and  even  in  can- 
cer, but  for  these  purposes  has  passed  entirely  out  of  vogue.  The  belief 
that  it  possesses  alterative  qualities  does  not  seem  to  be  well  founded. 

ADMINISTRATION. — The  preparations  of  conium  are  exceedingly  un- 
certain in  their  action.  Conine  itself  is  very  prone  to  undergo  sponta- 
neous change,  although  its  hydrobromate  is  said  to  be  a  stable  crystalline 
salt;  dose,  one-twentieth  to  one-twelfth  of  a  grain  (0.003-0.005  Gm. ). 
The  dose  of  the  extract  is  one  grain  (0.06  Gm.)  ;  of  the  tincture,  one- 
half  fluidrachm  (2  C.c.)  ;  of  the  fluid  extract  (FLUIDEXTRACTUM  CONII, 
U.  S. ),  one  to  two  minims  (0.06-0.12  C.c.)  :  all  of  which  must  be  ad- 
ministered in  increasing  doses  until  some  effect  is  experienced.  Of  these 
preparations  the  last  is  certainly  the  best. 

TOXICOLOGY.* — Sufficient  has  been  said  about  the  symptoms  caused 
by  conium.  After  death  from  it  no  distinctive  lesions  are  to  be  found, 
only  the  usual  indications  of  death  from  asphyxia.  The  treatment  con- 
sists in  the  immediate  evacuation  of  the  stomach  and  the  exhibition  of 
tannic  acid, — the  tannate  formed  is,  however,  probably  more  or  less 
poisonous, — with  the  use  of  external  heat  and  of  internal  stimulants  : 
artificial  respiration  should  steadily  be  maintained  so  long  as  there  is  the 
faintest  indication  of  cardiac  action.  No  physiological  antidote  is  known  ; 
but  strychnine  and  other  respiratory  stimulants  should  be  used. 


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"  According  to  H.  Hayashi  and  K.  Muto,  the  minimum  fatal  dose  of  conine  for  rabbits, 
intravenously  given,  is  between  fifteen  and  twenty  milligrammes. 

18 


274 


GENERAL  REMEDIES. 


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22.  GRAY Gl.  M.  J.,  1871,  188. 

23.  HARE B.  M.  S.  J.,  Nov.  1884. 

24.  MARSHALL     .   .   .  J.  P.,  1897,  xxii. 

25.  SMITH L.  M.  R.,  Oct.  1873. 

26.  Amer.    Journ.    Pharmacy, 

1881,  137. 

27.  HALDANE,  MAKGILL  and  MAVROGORDATA  . 

J.  P.,  1897,  xxi. 

ETHYL  NITRITE. 

1.  RICHARDSON     .   .  Brit,  and  For.  Med.-Chir. 

Rev.,  July,  1867. 

2.  LEECH     Med.  Chron.,  1869,  ix. 

SODIUM  NITRITE. 

1.  REICHERT  .   .    .   .  A.  J.  M.  S.,  Ixxx.  180. 

2.  ATKINSON  .   .   .   .  J.  A.  P.,  1888,  xxii. 
3-  L.  L.,  1883,  ii.  945. 

SPIRIT  OF  GLONOIN. 

1.  FIELD B.  M.  J.,  1880,  i.  406. 

2.  NOER T.  G.,  1887,  459. 

3.  BRUNTONand  TAIT  .  St.  Barthol.  Hosp.  Rep., 

xxii.  140. 

4.  HAY  ........  Pract.,  xxx.  422. 

5.  HENOCQUE    .  .   .  C.  R.  S.  B.,  1883,  v.  669. 

6.  KORCZYNSKI  .   .   .  S.  Jb.,  cxciii.  132. 

7.  HOGG Aus.  M.  Gaz.,  Oct.  1901. 

LOBELIA. 

1.  DRESER A.  E.  P.  P.,  1889,  xxxvi. 

2.  OTT B.  M.S.  J.,  1875;  P.M.  T., 

vi. 

3.  AFANASIEFF  .   .   .  L.  M.  R.,  Aug.  16,  1886. 

4.  NUNES S.  Jb.,  ccxxix. 

GELSEMIUM. 

i.  RINGER  and  MURRELL  .  L.  L.,  1876,  i.  83. 
a.  B.  M.  S.  J.,  1869,  iii.  185; 

1879,  ci.  18. 
3.  TAYLOR Richmond  and  Louisville 

Med.  Journ.,  1875,  606. 


DEPRESSO-MOTORS. 


275 


REFERENCES. —  Continued. 


4.  BARTHOLOW  .  .  .  Pract.,  v.  202. 

5.  RJNGER  and  MURRELL  .  L.  L.,  1875,  ii.  908. 

6.  OTT P.  M.  T.,vii.  289. 

7.  OTT P.  M.  T.,v.  691. 

8.  COURTRIGHT    .   .  Cincinnati  Lancet  and  Ob- 

server, 1876,  693. 


1.  HUSEMANN 

2.  COPLAND     . 


4.    HUTCHINSON 


I.  HUSEMANN 


TOBACCO. 

.   .  Handb.  d.  Toxicol.,  ii.  483. 
.   .  Diet,  of  Pract.  Med.,  art. 

Colic. 

An.  d'H.,  1861,  ii. 
.   .  M.  T.  G.,  1884,  i.  40. 


CONIUM. 

.   .  Die  Pflanzenstoffe,  269. 
Edinb.     Med.    and    Surg. 
Journ.,  1845. 


3. 
4. 

5.  VERIGO 

6.  PELVETTE   and 

7.  LAUTENBACH    . 

8.  KOLLIKER  .   .   . 

9.  FUNKE 


10.  GUTTMANN    . 

11.  LAUTENBACH 

12.  SCHULTZ     .  . 

13.  FLIESS 

14.  GUBLER 

15.  VON  PRAAG    . 


Sanitarian,  June,  1875. 
P.  J.  and  Tr.,  xvi.  102. 
S.  Jb.,  cxlix.  16.' 
MARTI  N-DAMOURETTE  .  A. 

G.  M.,6s.,  vi.  89. 
.  Proc.  Acad.  Nat.  Sciences, 

Phila.,  1875. 
.  V.  A.  P.  A.,  x.  228. 
Sb.   G.  W.,  Leipzig,  1859, 

xi.  23. 

.  B.  K.  W.,  1868. 
.  P.  M.  T.,  v. 
.  S.  Jb.,  cxlix.  16;  cxcv.  119. 

A.  Ph.,  1882,  in. 

B.  G.  T.,  1875. 

.  Journ.  f.  Pharmacodyn.,  i. 


16.  HOPPE  ......  Nervenwirk.  der  Heilmit- 

tel,  Leipzig,  1855.  i. 

17.  HAYASHI  and  MUTO  .  A.  E.  P.  P.,  xlviii. 


FAMILY    VII.— RESPIRATORY    STIMULANTS    AND 

DEPRESSANTS. 


FORMERLY  the  effect  of  a  drug  upon  the  respiration  was  universally 
estimated  by  its  influence  upon  the  rate  of  the  respiratory  movement.  If 
this  were  increased  the  drug  was  spoken  of  as  a  respiratory  stimulant ;  if 
it  were  decreased  the  drug  was  a  respiratory  depressant.  It  is  evident, 
however,  that  a  drug  may  increase  the  rate  and  yet  so  diminish  the 
extent  of  the  respiratory  movements  that  the  amount  of  air  taken  in  and 
out  of  the  lungs  would  by  it  be  absolutely  decreased.  Consequently,  as 
was  first  clearly  shown  by  H.  C.  Wood,  the  only  proper  test  as  to  the 
effect  of  a  drug  upon  the  respiration  is  the  amount  of  air  moved  by  the 
lungs  under  its  influence.  (See  Journal  of  Physiology,  1892.) 

It  is  worthy  of  note  that  the  respiratory  centre  is  anatomically  a  por- 
tion of  the  motor  tract  of  the  spinal  cord  ;  and  this  seems  to  be  carried 
out  by  its  physiological  relations  with  drugs,  apparently  all  substances 
which  are  stimulant  to  the  motor  side  of  the  spinal  cord  being  centric 
respiratory  stimulants,  and  those  which  are  depressant  to  the  motor  side 
of  the  spinal  cord  being  centric  respiratory  depressants. 

The  drugs  which  are  practically  used  as  respiratory  stimulants  are 
ammonia,  caffeine,  atropine,  cocaine,  and  strychnine.  For  the  discussion  of 
these  drugs  as  individual  remedies,  the  reader  is  referred  to  the  respective 
articles  upon  them.  Certain  comparisons,  however,  may  well  be  here 
instituted.  H.  C.  Wood  has  found  that  ammonia  is  too  fugitive  in  its 
action  and  too  violent  in  its  local  influence  upon  the  mucous  membranes 
to  be  of  practical  value  as  a  respiratory  stimulant.  In  contrasted  ex- 
periments atropine  appeared  to  be  the  most  powerful  in  its  influence  on 
the  normal  animal,  but  strychnine  apparently  had  more  power  in  assert- 
ing its  influence  against  opposition.  Thus,  although  atropine  seemed  to 
stimulate  respiration  more  than  did  strychnine  in  the  normal  dog,  yet 
in  the  chloralized  dog  the  effect  of  strychnine  was  distinctly  greater  than 
that  of  atropine.  Cocaine  was  found  to  be,  as  a  respiratory  stimulant, 
about  half-way  between  atropine  and  strychnine. 

Another  result  reached  was  that  it  was  possible  to  get  greater 
effect  by  the  consentaneous  use  of  two  drugs  than  by  one  alone.  Thus, 
in  the  heavily  chloralized  dog,  strychnine  given  up  to  the  point  of  in- 
cipient tetanus  could  only  raise  the  respiratory  function  to  a  certain 
height ;  whereas  injections  of  cocaine,  without  affecting  the  tetanoid  con- 
276 


RESPIRATORY   STIMULANTS   AND   DEPRESSANTS.     277 

dition,  would  increase  the  air-movements  perhaps  to  the  normal  or  even 
above  it.  A  practical  deduction  from  this  is  that  in  all  cases  in  which 
respiratory  stimulation  is  urgently  needed,  at  least  two  alkaloids  should  be 
used.  In  diseases  such  as  pneumonia  or  suffocative  bronchitis  we  have 
found  that  the  alternate  use  of  cocaine  and  strychnine  gives  the  best 
results  ;  a  dose  of  each  remedy  may  be  given  every  four  hours,  the 
patient  receiving  one  or  the  other  every  two  hours.  In  most  respiratory 
diseases  the  collateral  effects  of  atropine  interfere  very  greatly  with  its 
use.  On  the  other  hand,  in  narcosis,  especially  from  opium,  the  awaken- 
ing influences  of  the  drug  upon  the  cerebral  cortex  lend  to  it  especial 
value  ;  so  that  usually  in  narcotic  poisons  the  combination  of  atropine  and 
strychnine  is  probably  better  than  that  of  cocaine  and  strychnine. 

In  all  cases  of  severe  narcosis  the  alkaloidal  salts  should  be  used 
hypodermically. 

ASPIDOSPERMA— QUEBRACHO. 

Aspidosperma  is  the  bark  of  an  evergreen  South  American  tree,  Aspidosperma 
Quebracho-bianco.  It  contains  at  least  six  alkaloids,  aspidospermine,  aspidosper- 
matine,  aspidosamine,  quebrachine,  hypoquebrachine,  and  quebrachamine.  The  as- 
pidospermine  of  commerce  (amorphous  aspidospermine)  is  not  a  pure  principle, 
but  probably  contains  all  the  alkaloids  of  the  bark.  According  to  Merck  &  Co.,  it 
consists  principally  of  aspidosamine. 

PHYSIOLOGICAL  ACTION. — The  general  physiological  action  of  aspidosperma 
has  not  been  carefully  enough  studied  to  permit  definite  conclusions  concerning  its 
effects.  It  would  seem  that  the  various  alkaloids  have  entirely  different  effects  upon 
the  system  and  in  some  respects  are  even  antagonistic  ;  thus,  Schiffer l  has  found 
that  the  extract  of  quebracho-bianco  causes  in  the  rabbit  general  muscular  weakness 
with  greatly  diminished  reflexes  and  increased  frequency  in  breathing.  Eloy  and 
Huchard  *  found  that  aspidospermine,  quebrachine,  and  hypoquebrachine  produced 
violent  convulsions,  which  were  followed,  when  the  dose  was  large,  by  paralysis. 
According  to  Penzoldt,8  aspidospermine  produces  complete  motor  paralysis  in  the 
frog,  with  slowing  of  the  pulse. 

Respiration. — Penzoldt  *  was  the  first  to  describe  the  marked  action  of  que- 
bracho upon  the  respiration.  He  described  the  effect  produced  in  a  dog  as 
dyspnoea.  In  an  elaborate  research  by  Wood,  Jr. ,  and  Hoyt 5  on  the  effects  of  the  com- 
mercial aspidospermine,  it  was  shown  that  this  substance  produces  a  marked  increase 
in  both  rate  and  depth  of  the  respiration,  the  amount  of  air  moved  being  augmented 
in  some  cases  four  hundred  per  cent.  Secondary  depression  was  produced  only  by 
doses  large  enough  to  kill,  and  in  these  cases  the  stage  of  diminished  respiratory 
activity  was  very  short. 

Blood. — Penzoldt  noted  that  the  blood  in  the  veins  as  well  as  in  the  arteries  after 
the  administration  of  aspidosperma  had  a  bright  red  hue,  and  attributed  the  increase 
in  the  respiration  to  a  dyspnoea  brought  about  through  the  inability  of  the  corpuscles 
to  give  up  their  oxygen.  Wood,  Jr.,  and  Hoyt,  however,  believe  that  the  change  in 
the  blood  is  the  effect  rather  than  the  cause  of  the  increased  breathing.  They  were 
unable  to  find  any  spectroscopic  change  in  the  blood,  either  in  the  poisoned  animal 
or  when  the  aspidospermine  was  added  to  the  blood  outside  of  the  body  ;  they  were 
unable  to  note  any  diminution  of  the  oxidation  power  of  the  aspidospermine  blood 
towards  guaiac,  and  finally  they  noted  that  if  the  animal  was  asphyxiated  the  blood 
assumed  the  venous  hue  all  over  the  body. 

Circulation. — According  to  Wood  and  Hoyt,  commercial  aspidospermine  pro- 
duces a  marked  temporary  fall  of  the  blood-pressure,  which  was  permanent  if  the 


278  GENERAL   REMEDIES. 

dose  had  been  large.  During  the  period  of  low  blood-pressure,  it  was  found  that 
irritation  of  the  central  end  of  the  vagus  produced  a  rise  of  pressure,  showing  that 
the  vaso-motor  system  was  not  paralyzed.  As  the  pulse  was  not  slowed,  it  would 
seem  probable  that  aspidospermine  lowers  the  blood-pressure  by  a  depressant  action 
on  the  cardiac  muscle. 

Temperature. — Penzoldt  found  that,  although  quebracho  had  but  little  effect  on 
the  temperature  of  the  normal  animal,  in  a  dog  with  septic  fever  it  caused  marked 
diminution  in  the  temperature.  In  clinical  experiments,  however,  it  did  not  seem  to 
exercise  such  effect  in  human  fevers. 

THERAPEUTICS. — Aspidosperma  has  been  used  with  asserted  good  results  in 
various  forms  of  respiratory  embarrassment,  as  asthma,  emphysema,  and  bronchitis. 
It  is  even  stated  that  it  will  relieve  urcsmic  and  cardiac  dyspnoea. 

The  commercial  amorphous  aspidospermine  may  be  given  as  representing  prob- 
ably the  whole  effects  of  the  drug,  in  doses  of  from  one-eighth  to  one-half  grain 
(0.008-0.03  Gm.)  ;  the  dose  of  the  fluid  extract  is  a  quarter  to  one  Huidrachm 
(1-4  C.c.)  ;  of  the  solid  extract,  one  to  three  grains  (0.065-0.194  Gm.). 


REFERENCES. 

ASPIDOSPERMA.  3.  PENZOI.DT    .   .   .   .  B.  K.  W.,  1880,  jtvii.  565. 

1.  SCHIFFER     ....  A.  Ph.,  1883,  249.  4-  PENZOLDT    .   .   .   .  B.  K.  W.,  1879.  xvi.  269. 

2.  ELOV  and  HUCHARD  .  A.  de  P.,  1886,  vii.  236.          5-  WOOD,  Jr.,  and  HOYT  .  U.  P.  M.  B.,  Sept.  1903. 


ORDER   II.— CARDIANTS. 


FAMILY  I.— CARDIAC   STIMULANTS. 

THE  term  cardiac  stimulants  is  here  used  to  designate  a  number  of 
medicines  which,  when  given  internally,  increase  the  power  and  force 
of  the  circulation,  and  are  used  by  the  physician  for  such  purposes. 
There  are  some  substances  which  are  heart-stimulants  in  reality,  but 
which  possess  other  properties  in  so  great  a  degree  as  to  overshadow 
their  cardiac  relations,  and  are  therefore  not  used  by  the  physician  to 
affect  the  circulation.  Such  medicines  are  considered  in  connection  with 
those  powers  which  give  them  their  clinical  value,  and  are  not  included 
in  the  present  class.  Some  of  the  members  of  the  present  class  are  slow 
in  their  operation,  some  rapid.  Some  produce  increase  in  the  pulse- rate, 
some  lower  it.  It  is  evident,  then,  that  no  general  indications  can  be 
laid  down  for  their  use,  but  that  medicines  so  diverse  must  be  studied 
individually. 

AMMONIA. 

Ammonia  is  a  colorless,  irrespirable,  highly  irritant  gas,  of  a  strong 
alkaline  reaction,  extremely  soluble  in  water.  It  is  obtained  upon  a 
large  scale  as  a  waste  product  in  the  manufacture  of  coal-gas,  and  is 
official  in  watery  and  alcoholic  solutions  and  in  various  salts. 

PHYSIOLOGICAL  ACTION. — Local  Action  and  Elimination. — In  solu- 
tion, ammonia  is  a  very  powerful  irritant  and  even  escharotic,  producing, 
if  kept  in  contact  with  the  skin,  blistering,  and  finally  sloughing,  and 
causing  the  most  serious  disturbances  of  mucous  membranes  which  it 
reaches.  This  local  action  is  sufficient  to  interfere  with  its  absorption,  and 
it  is  difficult  to  produce  distinct  constitutional  symptoms  with  it  in  man. 
Its  volatility  and  the  extreme  fugaciousness  of  its  action  would  seem  to 
indicate  its  elimination  by  the  lungs  ;  but  Feltz  and  Ritter  *  were  not 
able  to  find  it  in  the  breath  of  poisoned  animals,  and  Magnus  has  appar- 
ently demonstrated  that  it  will  not  pass  through  the  alveolar  walls, 
Bence  Jones 2  believed  that  ammonia  is  oxidized  in  the  system  because  he 
found  that  its  administration  increases  the  acidity  of  the  urine  and  also 
the  amount  of  nitric  acid.  The  theory  that  some  portion  of  the  ammonia 
is,  in  conjunction  with  carbonic  acid,  converted  into  urea  is  held  by  some 
physiologists.* 

General  Action, — When  ammonia  is  injected  into  the  veins  of  animals 
in  considerable  quantities,  it  causes  violent  convulsions,  with  remarkable 
disturbances  of  the  respiration,  followed,  if  the  dose  has  been  large  enough, 

*  This  theory  is  of  such  purely  physiological  interest  that  it  is  dismissed  with  the  fol- 
lowing key  to  the  literature :  Arch.  f.  Exper.  Path.  u.  Pharm.,  ii.,  viii.,  x.  125,  x.  ii.  77; 
Zeitschr.f.  Physiolog.  Chem.,  ii.  29,  iv.  36;  Zeitschr.f.  Biol.,  xiv. 

279 


280  GENERAL  REMEDIES. 

by  death  in  a  very  short  time.*  Billroth8  states  that  the  temperature 
falls  enormously  in  animals  poisoned  with  ammonia. 

Cerebrum  and  Spinal  Cord. — Ammonia  has  no  effect  upon  the  cere- 
brum. The  tetanus  produced  by  it  in  the  lower  animals  is  accompanied 
by  great  increase  of  the  reflex  activity  (Funke4),  and  is  certainly  of 
spinal  origin,  since  it  occurs  below  a  section  of  the  spinal  cord  (Lange, 
Formanek)  and  is  not  prevented  by  tying  the  artery  of  a  limb  (Funke). 
It  would  therefore  appear  that  the  toxic  dose  of  ammonia  is  a  powerful 
stimulant  to  the  motor  spinal  cord.  Upon  the  sensory  cord  it  seems  to 
have  little  or  no  action. 

Respiration. — The  intravenous  injection  of  ammonia  causes  in  the 
animal  a  great  acceleration  of  the  breathing,  which  after  large  doses  may 
be  preceded  by  temporary  arrest  of  respiration  in  expiration.  The  cause 
of  this  arrest  is  uncertain,  Funke  observing  it  after  section  of  the  vagi, 
while  in  the  experiments  of  Lange  it  was  always  absent.  Section  of 
the  vagi,  however,  does  not  interfere  with  the  increased  rapidity  of  the 
breathing,  the  change  from  the  deep  breathing  of  divided  vagi  to  the 
extremely  rapid  respiration  of  ammonia-poisoning  being  colossal  (Funke). 
Further,  Binz 5  has  found  that  the  increase  of  the  respiratory  rate  in  chlo- 
ralized  rabbits  is  accompanied  by  a  great  increase  in  the  amount  of  air 
breathed.  Ammonia  is,  therefore,  a  powerful  direct  stimulant  to  the 
respiratory  centres. 

Circulation. — The  intravenous  injection  of  ammonia  both  in  normal 
and  curarized  animals  is  followed  by  an  immediate  fall  in  the  blood- 
pressure,  which  gives  way  to  a  very  decided  rise  if  the  dose  has  not  been 
too  large.  If,  on  the  other  hand,  an  overwhelming  amount  of  ammonia  or 
one  of  its  salts  is  employed,  the  fall  of  blood-pressure  continues  until  the 
arrest  of  the  heart  in  diastole.  When  the  dose  has  been  sufficient,  this 
cardiac  arrest  is  immediate.  In  the  experiments  of  Lange  and  of  Forma- 
nek, the  primary  fall  of  blood-pressure  occurred  after  section  of  the  spinal 
cord,  also  after  ligation  of  the  aorta  ;  without  doubt  it  is  due  to  the  direct 
action  of  the  concentrated  drug  upon  the  heart.  The  rise  of  pressure 
which  is  the  characteristic  effect  of  the  moderate  dose  of  ammonia  must 
be  due  to  a  stimulating  action  upon  the  heart  or  upon  the  peripheral 
vessels,  since,  according  to  both  Lange  and  Formanek,  it  occurs  after 
previous  section  of  the  cord.  The  experiments  of  Formanek,  in  which  it 
was  shown  that  if  the  thoracic  aorta  were  temporarly  ligated,  ammonia  still 
distinctly  elevated  the  blood-pressure,  demonstrate  that  the  drug  acts 
upon  the  heart  directly,  but  it  is  probable  that  the  muscle-fibres  of  the 
arterioles  are  also  affected  ;  so  that  the  conclusion  must  be  reached  that 
ammonia  is  a  primary  stimulant  both  to  the  heart  and  to  the  muscle-fibres 
of  the  arterioles,  although  when  in  overdose  it  is  a  paralyzant  to  both 
heart  and  arterioles. 

*  F.  Lange  (Archiv  f.  Experiment.  Path.  u.  Pharm.,  ii.,  368),  V.  Feltz  et  E.  Ritter 
(Journal  de  r Anatomic  et  de  la  Physiol.,  1874,  326),  and  Funke  (Pfiuger's  Archiv,  ix. 
426). 


CARDIAC  STIMULANTS.  281 

In  regard  to  the  action  of  ammonia  upon  the  pulse-rate,  the  evidence 
is  somewhat  discordant.  All  observers  seem  to  be  in  accord  that  the 
pulse  is  for  a  time  increased  in  rate,  which  increase  in  rate,  according  to 
Lange,  does  not  occur  after  section  of  the  spinal  cord,  and  according  to 
Formanek,7  is  prevented  by  extirpation  of  the  stellate  ganglion  of  the 
sympathetic.  The  increased  rate  appears,  therefore,  to  be  due  to  a  stimu- 
lating influence  upon  the  cardiac  accelerators.  Formanek  has  found  that 
at  the  time  of  the  highest  pressure  there  is  marked  slowing  of  the  pulse, 
which  is  prevented  by  section  of  the  vagi,  and  which  he  concludes,  there- 
fore, to  be  due  to  stimulated  inhibition.* 

According  to  Feltz  and  Ritter,  the  blood  of  a  dog  killed  by  ammonia 
is  incapable  of  absorbing  oxygen,  and  contains  much  less  than  the  normal 
amount  of  gas,  whilst  the  red  disks  resist  the  action  of  acetic  acid  to  a 
markedly  abnormal  degree. 

THERAPEUTICS. — Externally,  ammonia  is  much  used  as  a  constituent 
of  irritating  liniments,  and,  on  account  of  its  efficiency  and  cheapness,  is 
very  valuable.  By  inverting  a  watch-glass  full  of  the  stronger  water  of 
ammonia  upon  the  skin,  a  blister  may  be  raised  in  a  very  few  minutes  ; 
but,  as  the  effects  of  the  application  are  apt  to  be  severe,  the  use  of  it  is 
justifiable  only  under  rare  circumstances. 

Internally,  the  chief  indication  for  the  use  of  ammonia  is  failure  of 
tlie  heart '  s  action.  The  more  sudden  and  purely  functional  this  is  the 
more  efficacious  is  the  remedy,  which  should  in  such  cases  be  not  only 
administered  by  the  stomach,  but  also  inhaled  through  the  nostrils,  as 
the  local  action  of  the  irritant  vapor  upon  the  mucous  membrane  has  a 
very  arousing  influence.  When  the  failure  of  the  circulation  depends 
upon  a  slow  and  persistent  cause,  as  in  adynamic  fevers,  ammonia  is  not 
generally  useful,  but  may  be  employed  as  an  adjuvant  to  alcohol  in  the 
crisis  of  the  disorder.  As  a  stimulant,  ammonia  may  be  useful  in  poison- 
ing by  venomous  serpents,  but  the  statements  that  have  been  made  that 
it  is  antidotal  to  venom  have  no  foundation.  (For  detailed  discussion,  see 
the  tenth  edition  of  this  treatise. ) 

In  failure  of  the  heart  from  anaesthetics  f  or  other  poisons,  animal  or 
vegetable,  in  stidden  collapse  in  disease,  as  is  sometimes  seen  in  the  ex- 
anthemata, in  cholera,  and  not  rarely  in  pernicious  malarial  fever,  \  or 
after  surgical  operations  or  injuries,  hypodermic  injections  of  ammonia  § 
have  seemed  to  be  in  a  number  of  reported  cases  of  very  great  service. 

*  Formanek  believes  that  the  vagi  are  directly  stimulated,  but  his  tabulated  experi- 
ments seem  to  show  that  the  reduction  of  the  pulse-rate  is  inconstant,  and  it  is  possi- 
ble that  it  is  a  secondary  result  due  to  high  blood-pressure. 

t  Ringer  (Practitioner,  xxvii.)  finds  that  ammonia  added  to  the  frog's  heart  depressed 
with  chloroform,  iodoform,  etc.,  has  a  pronounced  effect  in  re-establishing  its  action. 

t  See  Zuelzer  (Revue  de  Therap.  Med.-Chir.,  July  i,  1872). 

?  See  Indian  Med.  Gaz.,  June  i,  1872;  Med.  Times  and  Gaz.,  Nov.  1872;  Chicago 
Med.  Journ.,  1872;  London  Med.  Record,  1873,  i. ;  L'Abeille  Med.,  Aug.  1874;  Berlin. 
Klin.  Wochenschrift,  No.  24,  1874;  Archives  Gen.,  1874,  ii. ;  Lancet,  1879,  ii.  158;  New 
York  Med.  Rec.,  xv.  532. 


282  GENERAL  REMEDIES. 

It  is  probable  that  in  many  of  these  instances  the  injections  have  largely 
acted  as  local  irritants,  reflexly  exciting  the  heart.  From  fifteen  to 
twenty-five  minims  of  the  aqua  ammoniae  fortior,  diluted  with  four  times 
its  bulk  of  water,  should  be  thrown  directly  into  a  vein  of  the  arm,  and 
repeated  in  fifteen  minutes  if  necessary. 

Ammonia  appears  to  have  a  tendency  to  act  upon  the  mucous  mem- 
brane of  the  lungs,  and  its  salts  are  used  as  stimulant  expectorants  in 
adynamic  pectoral  inflammations,  as  in  typhoid  pneumonia.  As  a  stimu- 
lant antacid,  it  is  frequently  of  service  in  cases  of  headache  from  gastric 
acidity. 

TOXICOLOGY. — Ingested  in  large  amount,  ammonia  acts  as  a  violent 
corrosive  poison,  the  symptoms  of  its  constitutional  action  being  en- 
tirely lost  in  those  caused  by  its  local  influence.  Violent  pain  in  the 
mouth  and  fauces,  in  some  cases  intense  burning  in  the  larynx  with  sense 
of  choking  and  great  difficulty  of  breathing  and  rapid  asphyxia  ;  more 
commonly  violent  abdominal  pain,  vomiting,  bloody  purging,  and  other 
symptoms  of  gastro-enteritis,  mark  its  escharotic  effects.  Death  from 
redema  of  the  larynx  may  occur  within  five  minutes.  More  usually  the 
fatal  result  is  wrought  out  more  slowly,  with  collapse  and  sometimes  con- 
vulsions secondary  upon  the  local  effects'.  In  some  cases  symptoms  of 
impending  suffocation,  resulting  in  death  from  asphyxia,  have  occurred, 
and  at  the  autopsy  intense  redness  and  congestion  of  the  bronchial  mucous 
membrane  have  been  present,  due  no  doubt  to  the  irritant's  having  found 
its  way  into  the  bronchi.  The  intellect  may  be  clear  to  the  very  moment 
of  death,  or  stupor,  and  finally  coma,  may  be  developed.  If  the  victim 
survive  for  a  few  hours,  recovery  usually  occurs,  but  the  convalescence  is 
commonly  protracted,  and  permanent  ill-health  may  result  from  the  de- 
structive lesions  produced  by  the  poison.  These  lesions  are  to  be  found 
not  only  in  the  respiratory  and  gastro-intestinal  tracts,  but  also  in  the 
kidneys.8  The  treatment  of  poisoning  by  ammonia  consists  in  the  neu- 
tralization of  the  ammonia  as  soon  as  possible  by  vinegar  or  other  dilute 
acid,  and  the  meeting  of  indications  as  they  arise.  If  the  oedema  of  the 
glottis  be  threatening,  tracheotomy  should  at  once  be  performed. 

ADMINISTRATION. — There  are  four  official  preparations  of  uncombined 
ammonia, — namely,  AQUA  AMMONITE  FORTIOR,  U.  S.  (Stronger  Water 
of  Ammonia),  contains  twenty-eight  per  cent,  of  gaseous  ammonia,  sp. 
gr.  0.897  ;  AQUA  AMMONITE,  U.  S.  (Water  of  Ammonia),  ten  per  cent., 
sp.  gr.  0.958;  SPIRITUS  AMMONITE,  U.  S.  (Spirit  of  Ammonia);  and 
SPIRITUS  AMMONITE  AROMATICUS,  U.  S.,  or  Aromatic  Spirit  of  Harts- 
horn. To  reduce  the  strength  of  the  first  of  these  preparations  to  that 
of  the  second  or  third  requires  the  addition  of  one  and  eight-tenths 
measures  of  water.  The  aromatic  spirit  contains  both  ammonia  and  its 
carbonate.  For  hypodermic  use  a  water  of  ammonia  or  a  solution  of  the 
ammonium  carbonate  is  to  be  preferred.  Dose  of  the  water  or  either 
spirit,  twenty-five  drops  to  a  teaspoonful  (1.5-3  C.c. ),  properly  diluted. 

Ammonium   Carbonate   (AMMONII   CARBONAS   U.   S.),   is  the  best 


CARDIAC  STIMULANTS.  283 

preparation  for  continuous  use.  It  occurs  in  white,  translucent,  fibrous 
masses,  which  on  exposure  become  opaque  and  efflorescent,  parting  with 
ammonia  and  passing  into  a  bicarbonate.  It  is  soluble  in  four  and  a  half 
times  its  weight  of  water,  and  may  be  given  in  solution  in  doses  of  from 
five  to  ten  grains  (0.3-0.6  Gm. ),  repeated  pro  re  nata.  The  effects  of  a 
single  dose  upon  the  system  probably  do  not  last  over  one  hour. 

Ammonium  Nitrate  (AMMONii  NITRAS,  U.  S.,  1890)  is  used  for  the 
preparation  of  nitrous  oxide  ;  Ammonium  Chloride  (AMMONII  CHLO- 
RIDUM,  U.  S. )  will  be  considered  under  Expectorants ;  Ammonium 
Iodide  (AMMONII  IODIDUM,  U.  S. )  under  Alteratives. 

CAMPHORA— CAMPHOR.  U.  S. 

Camphor  is  obtained  in  China,  Japan,  Cochin  China,  the  Sunda 
Islands,  etc.,  by  boiling  the  comminuted  wood  of  the  root,  stem,  and 
branches  of  the  Laurus  Camphora,  and  skimming  off  the  camphor  as  it 
rises  to  the  surface  of  the  water  when  cooled.  This  camphor  is  then 
partially  purified  by  sublimation,  and  comes  into  commerce  as  crude  cam- 
phor, which  occurs  in  grains  of  a  whitish  or  pinkish  color,  and  is  finally 
purified  by  sublimation  with  lime.* 

Refined  camphor  (or,  as  it  is  commonly  called,  camphor)  occurs  in 
disks  or  hemispherical  bowl-like  translucent  masses,  of  a  fibrous  or  granu- 
lar fracture.  Its  taste  is  hot  and  peculiar  ;  its  odor  very  strong  and  char- 
acteristic ;  it  is  volatile,  inflammable,  tough,  but  readily  pulverized  on  the 
addition  of  a  few  drops  of  alcohol  ;  melts  at  347°  F.  ;  is  soluble  in  one 
thousand  parts  of  cold  water,  f  in  one  part  of  strong  alcohol,  and  still 
more  soluble  in  chloroform  ;  thrown  upon  water,  a  granule  of  camphor 
floats,  and  exhibits  a  rotatory  movement. 

PHYSIOLOGICAL  ACTION. — Local  Action,  Absorption,  and  Elimina- 
tion.— Camphor,  though  primarily  a  local  irritant  and  stimulant,  probably 
has  a  narcotic  action  on  nerve-endings  in  the  mucous  membrane,  in  this 
way  relieving  intestinal  spasm.  It  is  slowly  absorbed  and  in  great  part  or 
altogether  oxidized  in  the  organism,  probably  changed  first  into  cam- 
pherol,  and  being  excreted  in  the  urine  as  campho-glycuronic  acid,  and 
amido-glycuronic  acid  (Schmiedeberg  and  Meyer1). 

General  Action. — The  ordinary  dose  of  camphor  (five  to  ten  grains) 
produces  when  taken  internally  a  feeling  of  warmth  in  the  stomach,  with 
in  some  cases  a  sense  of  slight  exhilaration  'and  quietness,  and  some,  but 
usually  not  a  pronounced,  acceleration  of  the  pulse.  In  doses  of  from 
twenty  to  thirty  grains  it  causes  lassitude,  giddiness,  lessening  of  the 

*  Borneo  camphor,  yielded  by  the  Dryobalanops  Camphora,  is  very  highly  valued  in 
the  East,  but  does  not  reach  this  country.  Stockman  has  found  that  both  it  and  the  Ngai 
camphor  of  China  act  on  the  organism  like  camphor.  See  Pellicani.17  A  number  of  other 
camphors,  such  as  Camphor- Cymol  Bornylamin,  Amido- Camphor,  Campherol,  have  been 
examined  by  various  investigators,  and  found  to  resemble  true  camphor  very  closely  in 
their  physiological  action. 

t  By  rubbing  the  camphor  up  with  magnesia  in  water,  the  latter  can  be  made  to  take 
up  much  more  than  one  part  in  one  thousand. 


284  GENERAL   REMEDIES. 

pulse-rate,  preceded  in  some  cases  by  a  brief  period  of  excitement.  After 
poisonous  doses  (thirty  to  sixty  grains)  the  symptoms,  which  are  toler- 
ably uniform,  are  as  follows  :  faintness,  headache,  vertigo,  confusion  of 
ideas,  burning  pain  in  the  stomach,  dyspnoea,  delirium,  spasms  deepening 
into  violent  convulsions,  coma,  with  complete  insensibility  and  absence  of 
all  reflexes  ;  the  pulse,  at  first  full  and  quick,  later  becomes  small  and 
sometimes  slow  ;  the  skin  is  cool,  pale  or  livid,  generally  bedewed  with 
sweat.  Glycosuria  has  been  noted  by  Stockman.  Sudden  unconscious- 
ness, with  or  without  convulsions,  has  been  in  some  instances  the  first 
manifestation  of  the  action  of  the  poison,  and  in  any  individual  case 
many  of  the  symptoms  detailed  above  may  be  wanting. 

Upon  the  lowest  forms  of  life  camphor  acts  as  a  very  feeble  germicide  ;  to  the 
articulates  it  is  a  violent  poison  ;  in  the  frog  it  produces  stupor  with  primary-  paral- 
ysis ;  in  birds,  according  to  Menghini,  it  causes  stupor  or  delirium,  with  epileptiform 
seizures  ;  and  in  mammals  vomiting,  violent  convulsions,  coma,  and  death,  appar- 
ently from  asphyxia,  follow  its  ingestion. 

Nervous  System. — The  only  evidences  that  the  small  dose  of  camphor 
has  any  influence  upon  the  intellectual  centres  is  the  slight  quietness 
which  it  sometimes  produces  in  man.  The  convulsions  which  are  caused  by 
the  toxic  dose  are  certainly  of  cerebral  origin,  since  C.  Weidemann,2  Hoff- 
mann (quoted  by  Weidemann),  and  Gottlieb*  have  shown  that  they  do 
not  spread  to  the  lower  segment  of  the  body  after  section  of  the  cord  ; 
and  R.  Stockman 4  has  found  that  in  the  rabbit  they  do  not  occur  after 
removal  of  the  cerebral  cortex.  The  convulsions  may  be  the  outcome 
of  irritation  of  the  psycho-motor  centres  in  the  cerebral  cortex,  but  the 
possible  methods  of  production  of  epileptiform  convulsions  are  not  suffi- 
ciently worked  out  to  warrant  positive  conclusions.  That  the  toxic  dose 
finally  produces  cerebral  paralysis  is  shown  by  the  coma  which  is  so  fre- 
quent a  symptom  of  camphor- poisoning. 

Spinal  Cord  and  Nerves. — The  action  of  small  doses  of  camphor  upon 
the  spinal  cord  is  still  unsettled,  but  it  is  probable  that  in  therapeutic 
doses  the  drug  acts  as  a  stimulant.  The  toxic  dose  of  camphor  depresses 
the  spinal  cord,  and,  as  was  first  shown  by  Weidemann,2  later  the  motor 
nerve-trunk,  beginning  with  their  peripheral  endings. 

In  the  frog  the  regular  course  of  paralytic  symptoms  produced  by  camphor 
are,  first,  loss  of  voluntary  movement,  the  reflexes  being  intact ;  second,  loss  of 
reflexes,  the  muscles  still  responding  when  the  motor  nerves  are  stimulated  ;  third, 
loss  of  function  in  the  motor  nerves,  the  muscles  responding  still  to  direct  stimuli. 
It  is  probable  that  the  loss  of  the  power  of  voluntary  movements  is  due  to  paralysis 
of  the  psycho-motor  centres,  although  it  may  be  the  outcome  of  some  interruption 
of  the  power  of  the  cord  to  carry  impulses  from  these  centres  to  the  motor  cells  in 
the  cord. 

According  to  the  experiments  of  Binz,6  Grisar,7  and  Gottlieb,  small  doses  of 
camphor  increase  reflex  activity  by  a  direct  action  upon  the  motor  side  of  the  spinal 
cord,  but  the  experiments  of  Stockman 4  appear  to  have  yielded  a  different  result, 
so  that  there  is  uncertainty  in  the  matter. 


CARDIAC   STIMULANTS.  285 

Muscles — Upon  the  muscles  themselves  camphor  exerts  a  very  feeble 
influence.  Locally  applied  to  the  muscles  in  the  form  of  solution  or  vapor, 
a  notable  effect  is  produced,  but  in  general  poisoning  this  is  not  evident. 
In  experiments  of  Cesare  Rossi,8  made  with  a  Mosso's  ergograph, 
camphor  given  internally  seemed  to  distinctly  increase  the  energy  and 
endurance  of  the  human  muscle,  but  in  other  cases  it  entirely  failed  to 
manifest  any  such  power  ;  so  that  if  it  have  any  direct  action  as  a  muscle 
stimulant,  such  action  must  be  feeble  and  uncertain. 

According  to  the  experiments  of  Meyer,5  the  absence  of  convulsions  in  camphor- 
poisoning  in  the  frog  cannot  be  explained  by  paralysis  of  the  spinal  cord  or  motor 
nerves,  since  before  these  conditions  are  developed  the  brain  is  profoundly  affected  ; 
nor  does  the  local  application  of  camphor  to  the  brain  in  the  frog  produce  convul- 
sions. Meyer  believes,  with  probable  correctness,  that  the  absence  of  convulsions 
is  due  to  the  rudimentary  development  of  the  cerebral  system  in  the  frog. 

Respiration. — According  to  Stockman  and  Binz,9  camphor  increases 
the  rate  of  respiration  greatly  ;  and  Lewin 10  found  that  the  amount  of 
respired  air  moved  was  markedly  increased  in  the  rabbit  by  it. 

It  would  appear,  therefore,  that  the  moderate  dose  of  camphor  is  a 
respiratory  stimulant,  and  as  there  is  probably  some  stimulation  of  the 
cord  by  the  drug,  the  inference  is  that  such  stimulation  is  due  to  an  action 
upon  the  respiratory  centres.  The  asphyxia  of  advancing  camphor- 
poisoning  indicates  that  the  respiratory  centres  finally  share  with  the 
other  motor  centres  of  the  spinal  cord  the  paralyzing  influence  of  the 
overwhelming  dose  of  the  drug. 

Circulation. — Although  there  has  been  much  positiveness  of  statement 
in  regard  to  the  action  of  camphor  upon  the  circulation  in  various  works 
of  pharmacology,  our  knowledge  of  its  action  is  really  incomplete  and 
uncertain.  It  has  been  directly  shown  by  the  concurrent  experimental 
results  of  Heubner  "  and  Harnack  and  Wittkowski,12  Weidemann,  Umpfen- 
bach,1J  Maki,u  and  Stockman  that  the  drug  decreases  the  rate  and  in- 
creases the  energy  of  the  contractions  of  the  isolated  frog's  heart,*  and  it 
may  be  considered  established  that  upon  the  frog's  heart  camphor  acts  as 
a  stimulant. 

The  statement  of  Heubner,  that  camphor  will  re-excite  the  movements  of  the 
frog's  heart  when  arrested  by  muscarin,  has  been  abundantly  confirmed.  Harnack 
and  AVittkowski  found  that  the  atropine  increases  the  contraction-rate  of  the  cam- 
phorized  heart,  that  stimulation  neither  of  the  vagus  nor  of  the  sinus  are  able  to 
arrest  cardiac  contraction,  and  that  muscle  paralyzants  like  the  soluble  copper 
salts  and  apomorphine  do  stop  the  heart's  beating. f  Bohme  M  found  that  camphor 
is  capable  of  causing  the  heart  arrested  by  chloral  to  recommence  beating.  The 
question  whether  the  drug  acts  upon  the  muscle  or  upon  the  ganglia  is  still  unan- 
swered, and  certain  actions  of  camphor  upon  the  frog's  heart  are  not  easily  explained. 

*  The  contrary  results  of  Alex.  Lewin  were  probably  due  to  the  use  of  overwhelming: 
doses,  in  such  doses  camphor  certainly  being  a  cardiac  depressant. 

t  In  repeating  Harnack  and  Wittkowski's  experiments  Stockman  failed  to  get 
satisfactory  results. 


286  GENERAL  REMEDIES. 

Thus,  in  Maki's  experiments  with  Williams's  apparatus,  some  minutes  after  the 
application  of  the  camphor  the  blood-pressure  fell  below  the  norm,  to  rise  very 
shortly  under  very  powerful  pulsations  of  the  heart.  Then  the  blood-pressure 
would  sink,  to  rise  again  in  a  little  while,  and  again  to  sink.  This  alternation 
would  occur  several  times.  These  experiments  of  Maki  have  apparently  not  been 
confirmed,  but  are  especially  interesting  in  relation  with  the  periodic  rise  and  fall 
of  blood-pressure  which  has  been  noted  in  mammals  by  Weidemann  and  others. 

The  action  of  camphor  upon  the  heart  of  the  frog  indicates  that  it  is  a 
cardiac  stimulant  in  the  mammal,  but  the  direct  positive  proof  of  this  is 
not  at  present  satisfactory.  At  times  camphor,  when  injected  in  small 
doses  directly  into  the  circulation  of  a  mammal,  increases  the  arterial 
pressure,  but  this  increase  is  never  constant  or  persistent  and  is  often 
absent,  the  characteristic  effect  of  the  camphor  being  depression  of  the 
arterial  pressure. 

It  is  of  course  possible  for  a  drug  to  stimulate  the  heart  and  yet  so  widen  out 
the  blood-paths  as  to  produce  no  rise  of  the  arterial  pressure,  and  Stockman 
reached  the  conclusion  that  camphor  depresses  the  vaso-motor  centres  and  probably 
produces  a  vascular  dilatation  which  masks  the  increased  action  of  the  heart, — a 
conclusion  which  is  in  accord  with  the  statements  of  both  Maki  and  Lewin,  that  in 
chloralized  animals,  when  the  vaso-motor  centres  are  deeply  paralyzed,  camphor 
elevates  the  pressure  ;  but  in  Lewin' s  experiments,  when  the  action  of  the  chloral 
was  profound,  the  pressure  failed  to  rise  under  the  influence  of  the  camphor  ;  and 
H.  Winterberg 15  determined  that  camphor  does  not  raise  the  arterial  pressure 
when  chloral  is  given  sufficiently  to  certainly  paralyze  the  vaso-motor  centres. 
Further,  all  attempts  to  demonstrate  the  stimulating  action  of  camphor  upon  the 
more  or  less  isolated  heart  of  the  mammal  have  so  far  yielded  contradictory  results. 
Gottlieb  obtained  an  apparent  stimulating  influence  from  the  camphor,  but  Winter- 
berg,  using  the  method  of  Langendorff  for  cardiac  isolation,  failed  entirely,  except 
in  two  experiments,  to  get  any  evidence  whatever  of  cardiac  stimulation.  Selig- 
man21  although  showing  in  some  cases  stimulation,  was  unable  to  demonstrate  any 
constant  influence  on  the  normal  mammalian  heart  but  found  that  camphor  was  ca- 
pable of  restoring  coordinate  beats  to  a  heart  thrown  into  fibrillary  contraction.* 

The  primary  rise  of  arterial  pressure  sometimes  produced  by  camphor 
is  probably  due  to  cardiac  stimulation.  Depression  of  the  blood-vessel 
system  is  the  characteristic  effect  of  the  full  dose  of  the  drug.  It  is  still 
uncertain  how  far  this  action  is  centric  or  peripheral.  Various  observers 
have  noted  that  the  local  application  of  camphor  causes  local  hyperaemia, 
believed  to  be  due  to  a  direct  action  of  the  camphor  upon  the  blood- 
vessels, and  it  seems  probable  that  Stockman  is  correct  in  believing  that 
the  fall  of  pressure  is  due  to  a  centric  action  on  the  vaso-motor  centres, , 
and  that  Winterberg  is  also  correct  in  believing  that  the  chief  action  of 

*  Rosenstein,  in  his  research,  concluded  that  camphor  has  a  stimulating  influence 
upon  the  heart,  though  a  very  fleeting  one.  With  borneol,  Pellicani "  obtained  fall  or 
periodical  oscillations  of  pressure.  Lewin  was  only  able  to  obtain  a  fall  of  the  arterial 
pressure,  and  Gottlieb  reached  the  conclusion  that  probably  camphor  increases  the 
capability  of  the  heart  to  respond  to  stimuli,  so  that,  whilst  the  normal  systole  is  not 
altered,  in  pathological  condition  there  is  such  an  increased  excitability  that  the  heart  is 
capable  of  great  efforts. 


CARDIAC   STIMULANTS.  287 

camphor  is  peripheral.      In  other  words,    it  is  probable  that  camphor 
depresses  both  the  walls  of  the  arterioles  and  the  vaso-motor  centres. 

As  is  shown  by  Weidemann,  during  the  convulsive  stage  of  camphor-poisoning 
there  is  a  marked  rise  of  the  arterial  pressure,  which,  however,  may  be  prevented  in 
great  measure  by  curarization  and  artificial  respiration,  and  is  therefore  evidently 
chiefly  due  to  the  convulsions  and  disturbances  of  breathing.  In  the  curarized 
animal  Weidemann  found  that  camphor  caused  remarkable  periodic  alternating 
elevation  and  fall  of  the  arterial  pressure,  which  are  prevented  by  section  either  of 
the  cord  or  vagi,  but  whose  nature  Weidemann  did  not  determine.  Stockman 
found  that,  at  least  with  Borneo  camphor,  such  action  is  extremely  inconstant,  and 
Winterberg  has  demonstrated  that  when  the  curarization  is  complete  the  oscillatory 
phenomena  are  absent,  so  that  they  are  probably  due  to  obscure  spasmodic  move- 
ments. 

Sexual  Function. — Camphor  has  been  largely  praised  by  some  med- 
ical practitioners  as  a  sexual  stimulant,  by  others  as  a  sexual  depressant. 
Almost  invariably,  however,  it  has  been  administered  in  combination  with 
other  more  potent  drugs,  to  which  any  apparent  influence  of  the  remedy 
has  probably  been  due.  There  is  certainly  no  experimental  and  appar- 
ently no  sufficient  clinical  reason  for  believing  that  camphor  acts  more  de- 
cidedly upon  the  sexual  centres  of  the  spinal  cord  than  it  does  upon  other 
nerve-cells  of  the  same  region. 

SUMMARY. — Camphor  causes  convulsions  through  its  effect  upon 
the  brain ;  the  therapeutic  dose  probably  has  a  quieting  influence  on 
the  cerebral  cortex.  In  large  doses  it  acts  as  a  depressant  to  the 
motor  cord,  -whilst  the  small  doses  are  probably  stimulant.  It  is  a 
stimulant  to  the  respiratory  centres,  and  probably  to  the  cardiac  mus- 
cle, but  does  not  greatly  raise  the  blood-pressure  on  account  of  its 
•widening  the  blood-vessels,  probably  both  peripherally  and  centrally. 

THERAPEUTICS. — Camphor  is  very  frequently  given  internally  as  an  an- 
tispasmodic,  to  quiet  restlessness  and  ' '  nervousness. "  It  is  also  employed 
in  certain  painful  affections  seen  in  those  persons  who  are  especially  liable 
to  the  condition  of  the  nervous  system  just  mentioned  :  thus,  it  is  often 
useful  in  nervous  headaches  and  dysmenorrhcea.  Indeed,  in  the  latter 
disease,  either  alone  or  combined  with  opium  in  bad  cases,  it  is  a  most 
valuable  drug,  but  must  be  given  freely.  In  diarrhoea  not  dependent 
upon  inflammation,  in  nervous  diarrhoea,  in  cholerine,  and  even  to  some 
extent  in  cholera,  camphor  is  an  efficient  remedy,  allaying  intestinal 
pain  and  spasm,  and  also  checking  intestinal  secretion.  It  enters  into  a 
large  proportion  of  the  popular  cholera-mixtures.  In  sudden  cardiac 
failure  and  in  adynamic  conditions  it  has  been  largely  used,  especially  in 
Germany  ;  but  whilst  it  probably  has  distinct  value  when  given  hypodermi- 
cally,  it  ought  not  to  be  relied  upon  to  the  exclusion  of  more  potent  drugs. 
According  to  Schilling,  thirty  grains  a  day  may  be  given  hypodermically 
in  the  profound  adynamia  of  acute  endocarditis,  typhoid  fever,  pneumonia, 
etc. ,  with  the  happiest  result.  The  use  of  large  doses  of  camphor  in 


288  GENERAL  REMEDIES. 

abnormal  sexual  excitement,  and  in  chordce,  has  about  passed  out  of  vogue, 
which  also  is  true  of  its  employment  in  severe  convulsive  disorders  such 
as  whooping-cough,  epilepsy,  and  puerperal  convulsions..  In  hysterical 
convulsions,  as  in  other  phenomena  of  similar  origin,  camphor  is  a  useful 
antispasmodic. 

Externally,  camphor  is  much  used  in  liniments  as  a  stimulant  applica- 
tion for  bruises,  sprains,  etc. 

TOXICOLOGY. — Although  camphor  has  in  many  cases  produced  very 
alarming  symptoms,  over  two  hundred  grains  of  it  have  been  taken  with- 
out permanent  result,  and  the  recorded  fatal  poisonings  are  very  few.  The 
only  ones  known  to  us  are — adult,  quantity  unknown  ; 18  sickly  infant,  ten 
grains  ; 19  child  two  years  old,  unknown  amount  ; M  fatal  abortion  produced 
by  three  drachms.* 

ADMINISTRATION. — Large  doses  (ten  to  fifteen  grains)  of  camphor 
are  best  administered  in  emulsion,  because  when  given  in  this  way,  being 
very  finely  subdivided,  they  create  as  little  irritation  as  possible,  and  are 
rapidly  absorbed  ;  smaller  doses  may  be  given  in  pill.  For  hypodermic 
use  a  ten  per  cent,  solution  in  olive  oil  should  be  preferred.  As  an  anti- 
spasmodic,  the  Camphor  Water  (AQUA  CAMPHORS,  eight-tenths  of  one 
per  cent. ,  U.  S. )  is  usually  preferred  ;  its  dose  is  half  a  fluidounce  to  two 
fluidounces  (15-60  C.c. ),  but,  when  a  decided  effect  is  desired,  the  Spirit 
of  Camphor  (SPIRITUS  CAMPHORS — ten  per  cent. ,  U.  S. )  is  more  effec- 
tive ;  its  dose  is  fifteen  to  thirty  minims  (1-2  C.c.).  For  external  use 
are  official  the  LINIMENTUM  CAMPHORS  (camphor  one  part,  cotton-seed 
oil  four  parts,  U.  S. )  and  the  LINIMENTUM  SAPONIS,  or  Soap  Liniment, 
U.  S. , — a  mild  liniment  very  popular  either  by  itself  or  as  the  basis  of 
more  stimulating  preparations. 

The  Oil  of  Camphor  occurs  in  our  market  as  a  reddish  or  yellowish-brown 
liquid,  having  a  strong  odor  of  camphor,  and  a  hot,  camphoraceous  taste.  It  con- 
tains camphor  in  solution,  and  is  probably  equivalent  to  it  in  physiological  action, 
except  that  it  is  locally  more  stimulating,  and  preferable  in  intestinal  disorders. 
Dose,  five  to  ten  drops  (0.3-0.6  C.c.). 

ACIDUM  CAMPHORICUM,  U.  S. — Camphoric  Acid  is  produced  by  boiling  cam- 
phor with  concentrated  nitric  acid.  It  occurs  in  small  white,  acicular  or  scaly  crys- 
tals, free  from  odor,  of  a  feebly  acid  taste,  sparingly  soluble  in  cold,  freely  in  hot, 
water,  also  in  alcohol,  ether,  and  fatty  oils.  It  was  originally  proposed  by  Fiir- 
bringer J  as  an  antiseptic  of  practical  value  for  the  disinfection  of  the  intestinal 
canal,  and  in  the  treatment  of  tuberculosis  and  ammoniacal  cystitis :  as  first  noticed 
by  Wittkowski  it  is  a  very  valuable  antihydrotic  in  the  night-sweats  of  phthisis ; 
how  it  acts  in  these  cases  has  not  been  determined.  Max  Reichert,  Niesel,  and 
other  physicians  have  found  it  very  serviceable  as  a  local  application  in  the  treat- 
ment of  tubercular  and  other  catarrhs  of  the  upper  and  lower  air-passages. 

According  to  Bohland,*  camphoric  acid  is  rapidly  eliminated,  the  whole  of  a 

*  Cases,  Edinburgh  Med.  Journal,  May,  1873 ;  The  Clinic,  March,  1873 ;  Wiener 
Medizinische  Presse,  1874,  258;  Berlin.  Klin.  Wochens.,  Sept.  1873-74;  Trans.  Land. 
Clin.  Soc.,  1874,  27;  London  Lancet,  1876,  ii.  71;  British  Med.  Journ.,  Feb.  1875,  1877,  i. 
607,  Sept.  1895;  June,  1896;  St.  Petersburg  Med.  Wochens.,  1897,  xiv. 


CARDIAC   STIMULANTS.  289 

single  dose  escaping  from  the  kidneys  in  the  course  of  five  hours  unaltered.  In  cys- 
titis, fifteen  grains  ( i  Gm. )  may  be  given  three  or  four  times  a  day  ;  for  night- 
sweats,  fifteen  to  thirty  grains  may  be  administered  at  bedtime,  or,  when  the  sweat 
occurs  late  in  the  night,  the  dose  may  be  divided,  the  patient  being  wakened  to 
take  the  last  dose  after  midnight.  Gastric  irritation  and  even  vomiting  have  been 
noted  after  thirty  grains,  and  Niesel  saw  severe  renal  irritation  in  a  patient  who  had 
taken  in  four  weeks  fifty  grammes. 

Oxycamphor — This  oxidation  product  of  camphor  is  a  white,  crystalline  powder, 
soluble  to  two  per  cent,  in  cold  water  ;  is  alleged  to  have  a  calmative  action  upon 
the  respiratory  centres  whilst  strengthening  the  cardiac  muscle  and  the  central  and 
peripheral  vaso-motor  nervous  system.  It  has  been  used  with  asserted  excellent 
results  in  dyspnoea  from  cardiac  weakness,  and  from  tubercular  and  other  chronic 
diseases  of  the  lungs.  Dose,  eight  to  sixteen  grains  (0.5  to  i  Gm.)  two  or  three 
times  a  day.  (See  M.  R.,i897,  1899,  1901). 

ALCOHOL.     U.  S. 

ALCOHOL  ABSOLUTUM,  U.  S.  (Absolute  Alcohol), — i.  <?.,  ethyl  alcohol 
containing  not  more  than  one  per  cent,  by  weight  of  water, — is  a  colorless, 
volatile  liquid,  boiling  at  172°  F. ,  not  congealed  by  a  cold  of  — 166°  F. , 
and  having  the  specific  gravity  of  0.797.  It  is  used  only  for  chemical 
purposes.  ALCOHOL,  U.  S. ,  contains  94.9  per  cent,  by  volume  of  abso- 
lute alcohol,  and  has  the  specific  gravity  of  0.816  ;  and  ALCOHOL  DILU- 
TUM,  U.  S.  (Diluted  Alcohol),  contains  48.9  per  cent,  by  volume  of 
absolute  alcohol,  and  has  the  specific  gravity  of  0.936. 

Alcohol  also  exists  in  the  official  SPIRITUS  FRUMENTI,  or  WHISKEY, 
and  SPIRITUS  VINI  GALLICI,  or  BRANDY,  which  are  obtained  respec- 
tively by  the  distillation  of  fermented  grain  and  of  fermented  grapes, 
and  should  contain  from  forty-eight  to  fifty-six  per  cent,  of  absolute 
alcohol,  and  in  the  official  VINUM  RUBRUM,  or  Red  Wine,  and  VINUM 
ALBUM,  or  White  Wine.  For  medicinal  use,  brandy  should  be  at  least 
four  and  whiskey  at  least  two  years  old. 

Local  Action. — Alcohol  is  a  very  active  irritant,  but  is  not  corrosive. 
It  is  also  a  pronounced  germicide,  which  when  in  proper  concentration  is 
capable  of  killing  all  protoplasms. 

According  to  the  researches  of  C.  Harrington  and  H.  Walker,71  against  dry 
bacteria  absolute  alcohol  and  ordinary  commercial  alcohol  are  wholly  devoid  of 
bactericidal  power,  whilst  forty  per  cent,  alcohol  is  effective  within  five  minutes 
against  most  non-sporulating  pathogenic  bacteria.  In  order  to  destroy  some  of  the 
strongly  resisting  bacteria,  whether  dry  or  moist,  sixty  to  seventy  per  cent,  alcohol 
is  necessary.  Preparations  of  alcohol  more  concentrated  than  seventy  per  cent,  do 
not,  however,  act  more  powerfully  upon  bacteria  than  do  the  weaker  preparations, 
so  that  for  the  practical  disinfection  of  a  wound  sixty  to  seventy  per  cent,  alcohol 
should  be  preferred  ;  the  contact  should  be  maintained  for  at  least  five  minutes. 

Absorption  and  Elimination. — Alcohol  is  absorbed  with  great  rapidity 
by  the  stomach,  but,  as  has  been  shown  by  Von  Mering,1  is  also  hurried 
on  into  the  intestines.  It  is  without  doubt  taken  up  freely  into  the  whole 
length  of  the  alimentary  tract.  In  Baum's*  experiments  symptoms  of 
intoxication  appeared  in  a  horse  fifteen  minutes  after  its  injection  into  the 

19 


290  GENERAL  REMEDIES. 

rectum.  (For  a  study  of  the  point  of  elimination  in  the  system,  see  page 
298.*) 

General  Action. — The  phenomena  which  follow  the  ingestion  of  alco- 
hol are,  unfortunately,  so  well  known  as  to  make  any  description  of  them 
here  unnecessary,  and  we  shall  at  once  proceed  to  the  discussion  of  the 
action  of  the  drug  upon  different  portions  of  the  organism. 

Nervous  System. — We  have  not  met  with  a  close  experimental  study 
of  the  order  in  which  the  nervous  centres  are  affected,  but  it  is  scarcely 
doubtful  that  alcohol  acts  upon  them  as  does  ether,  except  that  the 
latter  substance,  being  much  more  volatile  than  alcohol,  is  consequently 
absorbed  and  eliminated  much  more  rapidly,  so  that  its  influence  is 
more  evanescent.  We  know  by  experiment  that  the  vapor  of  alcohol  is 
capable  of  producing  the  stupor  known  as  anaesthesia,  and,  further, 
that  this  anaesthesia  may  be  deepened  into  death,  accompanied  by  all 
the  phenomena  of  fatal  ether-narcosis.  It  is  probable  that  there  is  an 
early  stage  in  the  action  of  alcohol  in  which  not  only  the  cerebral  but 
it  may  be  even  the  spinal  centres  are  stimulated,  but  certainly  in  the 
advanced  stages  of  alcohol-poisoning  muscular  relaxation  and  the  loss 
of  reflex  activity  are  altogether  or  in  part  due  to  the  sedative  influence 
upon  the  motor  cord.  The  theory  of  a  primary  stimulation  gains 
plausibility  from  the  experiments  of  Mommsen,5  in  which  it  was  found 
that  the  excitability  of  the  peripheral  motor  nerve  is  primarily  increased 
by  the  local  action  of  alcohol.  The  observation  of  Dogiel,  that  in  the 
alcoholized  dog  both  sensory  and  motor  nerves  are  markedly  depressed, 
without  doubt  holds  good  for  acute  alcoholism  in  man.  Whether  this 
depression  is  due  directly  to  the  alcohol  or  to  the  changes  produced  by  it 
is  uncertain.  It  cannot  be  denied  that  the  continuous  effect  of  large 
doses  of  alcohol  upon  the  nervous  tissue  is  depressant. 

The  original  experiments  of  Heinrich  Dehio,4  showing  that  changes 
can  be  demonstrated  in  the  ganglionic  cells  of  the  brain  in  animals  killed 
by  the  large  dose  of  alcohol,  have  been  repeated  and  extended  by  Colin 
C.  Stewart 5  with  corroborative  results. 

Circulation. — The  subject  of  the  action  of  alcohol  upon  the  circula- 
tion is  one  which  has  given  rise  to  a  great  deal  of  investigation,  but  con- 
cerning which  the  present  evidence  is  so  contradictory  and  imperfect,  and 
so  affected  by  controversy,  as  to  make  positive  conclusions  unwarrantable. 
From  time  immemorial  alcohol  has  been  and  still  is  used  clinically  as  a  cir- 
culatory stimulant,  and  this  view  of  the  matter  has  been  supported  by 
much  physiological  evidence,  and  is  still  held  by  eminent  pharmacologists, 
whilst  other  pharmacologists  teach  that  alcohol  has  no  action  upon  the 
circulation  unless  given  in  toxic  doses,  when  it  always  lessens  the  force 
of  the  blood-current. 

Experiments  upon  the  lower  animals  have  yielded  results  which  are  so  contra- 
dictory that  the  diversity  can  hardly  be  accounted  for  by  the  theory  formerly  held 

*  See  Chhtenden,  Mendel,  and  Jackson  (Amer.  Journ.  Physiol.,  1898,  i.). 


CARDIAC   STIMULANTS.  291 

by  the  writers  of  this  book,  namely,  that  the  contradictions  have  been  due*  to  the 
use  of  different  doses  of  alcohol.  It  is  nevertheless  true  that  much  of  the  diver- 
sity of  result  depends  upon  the  varying  amounts  of  alcohol  administered.  Thus, 
the  results  obtained  by  H.  Zimmerberg,  who  found  that  alcohol  reduces  both  the 
rate  and  force  of  the  pulse,  evidently  depended  upon  his  employing  toxic  doses  of 
alcohol.  The  same  objection  holds  with  the  experiments  of  Z.  Gutnikow,6  in  which 
were  given  to  dogs  doses  of  two  hundred  and  fifty  grammes*  of  from  fifty  to  seventy 
per  cent,  alcohol,  with  a  marked  fall  both  in  the  arterial  and  in  the  venous  pressure. 
There  was  also  in  Gutnikow's  observations  a  fall  in  the  intra-cardiac  pressure,  both 
auricular  and  ventricular.  In  some  cases  the  intra-cardiac  fall  preceded  the  fall  of 
the  arterial  pressure.  In  the  experiments  of  J.  Dogiel  and  of  J.  D.  Castillo  and  of 
Kochmann 93  the  intravenous  injection  of  small  doses  of  alcohol  produced  a  more 
or  less  distinct  rise  of  the  arterial  pressure,  which  was  followed,  when  the  dose  was 
large  enough,  by  a  fall  of  the  arterial  pressure.  This  result  is  in  general  accord 
with  that  obtained  by  S.  Potts  Eagleton. 8  f 

In  favor  of  the  view  that  small  doses  of  alcohol  elevate  blood-pressure  may  be 
considered  the  works  of  Sjetschenow,  of  Dogiel,  of  Ronchi  and  Salvioli,  and  other 
experimenters  ;  whilst  John  J.  Abel  J  is  positive  in  his  conviction  that  alcohol  does 
not  in  any  dose  put  up  the  arterial  pressure. 

When  evidence  concerning  the  action  of  a  drug  is  contradictory,  it  is 
easy  to  deny  the  accuracy  of  experimentation,  but  usually  the  contradic- 
tory results  really  depend  upon  uncertainty  of  action  in  the  drug.  In  a 
large  number  of  experiments  made  by  H.  C.  Wood  and  D.  M.  Hoyt9* 
upon  normal  dogs  and  upon  dogs  suffering  from  an  infective  fever,  it  has 
been  found  that  usually  even  in  small  doses  alcohol  does  not  increase  the 
arterial  pressure  ;  but  in  exceptional  cases  it  has  such  action,  this  too  at  a 
time  when  the  unusual  action  is  not  to  be  accounted  for  by  the  presence 
of  muscular  or  other  excitement,  or  perceptible  cause  other  than  that  of 
the  alcohol  itself. 

The  results  of  circulatory  sphygmomanometric  studies  upon  man  are 
similar  to  those  which  have  been  obtained  in  experiments  upon  the  lower 
animals.  Thus  Cabot,  in  a  very  elaborate  study,  reaches  the  conclusion 
that  neither  in  health,  nor  yet  in  fever,  does  alcohol  put  up  the  arterial 
pressure.  J.  Swientochowsky  experimented  with  Gartner's  tonometer 
in  cases  of  arterial  sclerosis,  phthisis,  and  cardiac  disease  ;  was  not  able  to 
get  lessening  of  the  arterial  pressure  by  the  administration  of  alcohol. 
Binz59  concludes  that  the  taking  of  forty  or  fifty  c.c.  of  sherry  does  in 
health  increase  arterial  pressure.  The  concordance  of  evidence  seems  to 
us  to  prove  that  alcohol  ordinarily  does  not  increase  arterial  pressure, 

*  The  weight  of  the  dogs  is  not  given,  and  the  amount  per  kilo,  therefore,  cannot  be 
estimated. 

t  Eagleton's  experiments  were  made  with  a  continuous  injection  of  alcohol,  and  in 
two  of  them  the  results  were  somewhat  different  from  those  ordinarily  obtained.  The 
reason  of  this  is  not  obvious.  None  of  his  dogs  appear  to  have  been  curarized,  and  the 
peculiar  method  of  experimentation  requires  the  results  to  be  interpreted  with  great 
care. 

J  A  very  full  and  elaborate  critique  of  the  literature  of  the  subject,  by  Professor  Abel, 
may  be  found  in  the  Physiological  Aspect  of  the  Liquor  Problem,  vol.  ii.  1903,  a  critique 
which  is  very  able,  but  in  which  there  is  too  much  of  the  denying  of  the  possibility  of  the 
existence  of  the  other  side  of  the  shield  to  give  entire  satisfaction. 


292  GENERAL  REMEDIES. 

although  exceptionally,  from  causes  which  have  not  been  made  out,  it 
may  have  such  action. 

A  drug  may  stimulate  the  heart  and  yet  have  no  constant  effect  upon 
the  blood-pressure,  because  it  depresses,  either  through  the  vaso-motor 
centres  or  through  action  upon  the  blood-vessel  walls,  the  vaso-motor 
condition.  The  solution  of  such  a  problem  would  naturally  lead  to  a 
study  of  the  action  of  the  drug  upon  the  heart  itself  and  upon  the  blood- 
vessels. 

Studies  have  been  made  upon  the  isolated  frog's  heart  by  Umpfenbach  (1881), 
by  Ringer  and  Sainsbury  (1883),  by  Maki  (1884),  and  by  Dresser  (1888),  with  the 
general  conclusion  that  alcohol  is  a  direct  depressant  to  the  cardiac  muscle  ;  whilst 
Castillo  (1880),  Eagleton  and  Cerna  have  reached  opposite  conclusions  ;  so  that  the 
present  experimental  evidence  on  the  subject  is  contradictory  so  far  as  the  isolated 
frog's  heart  is  concerned.  Martin90  and  Hemmeter,91  experimenting  upon  the  iso- 
lated mammalian  heart,  reached  the  conclusion  that  blood  containing  one-eighth 
per  cent,  by  volume  of  absolute  alcohol  has  no  immediate  action  upon  the  isolated 
heart  ;  but  that  when  one-fourth  per  cent,  is  present  the  work  done  by  the  heart  is 
diminished  within  a  minute.  The  abnormality  of  the  conditions  of  these  investiga- 
tions is  shown  by  the  fact  that  cutting  away  the  pericardium  was  found  by  Martin  to 
stop  the  depressing  action  of  even  one-half  per  cent,  of  alcohol ;  whilst  Hemmeter 
observed  that  the  alcohol  produced  intra-cardiac  regurgitant  murmurs  and  hem- 
orrhage into  the  cardiac  tissue, — results  not  seen  in  ordinary  alcoholic  intoxication. 
Loeb  95  in  an  elaborate  study  points  out  a  number  of  sources  of  error  in  the  ordinary 
methods  of  studying  the  changes  in  the  activity  of  the  isolated  mammalian  heart, 
and  reaches  the  conclusion  that  alcohol  in  the  proportion  of  0.13  100.30  per  cent, 
by  volume  exercises  a  distinct  although  not  powerful  stimulant  influence  upon  the 
heart,  while  concentrations  of  more  than  one  per  cent,  are  depressant. 

In  his  critique  upon  the  work  upon  the  frog's  heart,  Abel  condemns  the  work 
of  Castillo,  Eagleton,  and  Cerna  as  inaccurate.  Our  own  belief,  as  the  result  of 
considerable  experimental  work  with  the  Williams  and  Kronecker  apparatus  on  the 
isolated  frog's  heart,  is  that  none  of  the  work  so  far  done  on  the  isolated  heart  of 
the  frog  can  be  accepted  as  final.  The  reasons  for  this  judgment  it  is  impossible  to 
discuss  in  a  volume  like  the  present. 

In  the  present  confusion  of  evidence,  one  experimental  fact  to  which 
we  have  not  yet  alluded  seems  to  afford  firm  ground  for  deduction  ; 
namely,  that  after  section  of  the  spinal  cord  alcohol  not  only  causes  rise 
of  the  arterial  pressure  but  causes  a  rise  which  is  a  very  distinct  and  a 
very  constant  phenomenon.  Originally  noted  by  Castillo,  this  fact  has  been 
confirmed  by  Abel  in  numerous  experiments,  and  also  by  H.  C.  Wood 
and  D.  M.  Hoyt.  We  know  of  no  way  of  explaining  the  action  of  a  drug 
which  is  unable  to  put  up  arterial  pressure  in  the  normal  animal,  but  does 
cause  rise  of  pressure  when  the  vaso-motor  centres  have  been  paralyzed 
by  section  of  the  spinal  cord,  except  on  the  theory  that  the  drug  is  a  stim- 
ulant to  the  heart  and  a  paralyzant  to  the  vaso-motor  centres.  This  conclu- 
sion in  regard  to  alcohol  is  confirmed  by  the  observations  of  J.  C.  Hem- 
meter,9  and  by  Wood  and  Hoyt  made  with  the  stromuhr,*  that  alcohol 

*  The  velocity  of  the  blood-current  in  the  arterial  system  depends  upon  the  relations 
between  the  propulsive  force  and  the  resistance :  the  greater  the  propulsive  force  the 
greater  the  velocity,  the  greater  the  resistance  the  less  the  velocity.  (The  term  velocity 


CARDIAC   STIMULANTS.  293 

increases  the  velocity  of  the  blood  current.  Moreover,  in  two  experi- 
ments on  the  human  being  with  the  arm  plethysmograph,  by  Wood  and 
Hoyt,  direct  evidence  was  obtained  of  dilatation  of  the  blood-vessels. 

The  fall  of  the  arterial  pressure  caused  by  the  large  dose  of  alcohol 
occurs  after  section  of  the  cord,  and  must,  therefore,  at  least  in  part,  be 
due  to  direct  action  upon  the  heart  itself  or  muscle-fibres  in  the  vessel- 
walls,  a  conclusion  which  is  in  conformity  with  the  experiments  of  Castillo, 
in  which  stimulation  of  a  sensitive  nerve  caused  rise  of  pressure,  proving 
that  the  vaso-motor  system  was  still  capable  of  responding  to  stimuli. 
Certainly  the  known  action  of  alcohol  upon  the  excised  frog's  heart,  and 
the  diastolic  arrest  produced  by  it  in  the  mammal,  prove  that  in  over-dose 
alcohol  is  a  direct  depressant  to  the  heart ;  it  probably  has  also  depressing 
influence  upon  the  muscle-fibres  in  the  walls  of  the  vessels  and  the  vaso- 
motor  centres. 

Blood. — There  seems  to  be  little  reason  for  supposing  that  alcohol  in 
therapeutic  dose  has  an  appreciable  effect  upon  the  blood,  but  as  long 
ago  as  1841  C.  H.  Schulz  10  observed  that  mixed  with  the  blood  outside 
of  the  body  it  not  only  causes  coagulation,  but  also  separation  of  the 
haemoglobin  from  the  corpuscles.  It  is  probable  that  to  the  action  of  the 
alcohol  upon  the  haemoglobin  is  due  the  fact  noted  by  Schmiedeberg ll 
that  alcohol  mixed  with  blood  lessens  its  ability  to  yield  oxygen  in  the 
presence  of  a  reducing  agent.  Jaillet  and  Hay  em  state  that  in  rapid 
alcoholic  poisoning  in  animals  extensive  alteration  in  the  blood-corpuscles 
can  be  discovered,  many  of  these  bodies  being  shrivelled  and  altered  in 
form,  with  yellow  precipitates  of  haemoglobin  in  their  interior. 

Temperature. — Owing  no  doubt  to  the  sensations  of  warmth  induced 
by  its  local  action  on  the  stomach  and  by  the  increased  activity  of  the 
circulation  in  the  extremities,  alcohol  was  formerly  looked  upon  as  a  pro- 
moter of  animal  heat.  This  view  was  questioned  as  early  as  1848  by 
Dum£ril  and  Demarquay,  and  has  been  studied  and  written  about  to  an 
enormous  extent.  The  matter  has  been  so  thoroughly  worked  out  that 

is  here  used  to  express  the  amount  of  blood  passing  a  given  point  in  a  given  length  of 
time.)  It  will  be  seen  at  once  that  the  arterial  pressure  and  velocity  are  not  synonymous 
or  necessarily  accordant.  If,  for  instance,  a  drug  increases  the  resistance  without  affect- 
ing the  propulsive  force,  the  blood-pressure  may  be  raised  or  remain  almost  unchanged 
while  the  velocity  will  decrease.  Hemmeter  gives  the  following  as  possible  variations 
to  whkrh  the  main  factors  in  the  making  of  velocity  and  arterial  pressure  are  subject : 

1.  The  energy  of  the  heart  contractions  remains  the  same  and  the  resistance  (a)  in- 
creases, then  blood-pressure  increases  and  velocity  decreases,    (d)  Resistance  decreases, 
then  blood-pressure  decreases  and  velocity  increases. 

2.  The  energy  of   the  heart  activity  increases,  and  the  (a)  resistance  is  the  same, 
then  blood-pressure  and  velocity  increase,      (d)  The  resistance  increases,  then  blood- 
pressure  increases  and  velocity  remains  the  same,     (c )  The  resistances  diminish,  then 
blood-pressure  remains  the  same  and  velocity  increases. 

3.  The  energy  of  the  heart  activity  decreases  and  at  the  same  time  (a)  the  resistance 
is  the  same,  then  blood-pressure  and  velocity  are  reduced,     (d)  The  resistances  are 
correspondingly  greater,  then  blood-pressure  remains  the  same  and  velocity  decreases. 
(c )  The  resistances  are  correspondingly  smaller,  then  blood-pressure  sinks  and  velocity 
is  the  same. 


294  GENERAL  REMEDIES. 

it  does  not  seem  wise  to  do  more  here  than  give  results,  and  to  refer  the 
reader  who  is  desirous  of  following  up  the  literature  of  this  subject  to  the 
tenth  edition  of  this  treatise. 

In  the  lower  animals  small  doses  of  alcohol  produce  an  increase  of  the 
bodily  temperature,  which  rarely  in  mammals  reaches  more  than  i  °  F.  and 
in  birds  i°  F.  Larger  doses  of  alcohol  produce  a  fall  of  temperature  in 
the  animal  proportionate  to  the  size  of  the  dose.  According  to  Ruge,11 
when  the  dose  has  not  been  sufficient  to  cause  distinct  intoxication,  the 
fall  usually  amounts  to  from  £°  C.  to  f  °  C. ,  rarely  reaching  one  degree. 
When  there  is  distinct  narcosis  the  fall  may  amount  to  3°  C. ,  or  with  a  lethal 
dose  to  5°  C.  Bouvier  and  other  observers  have  found  that  the  effects 
of  large  doses  of  alcohol  are  even  more  marked  in  animals  suffering  from 
pyaemic  fever  ;  the  reduction  of  temperature  may  amount  to  8.5°  C.,  and 
the  fever  be  altogether  put  aside  by  the  narcotic  dose.  The  effect  of 
alcohol  upon  the  temperature  in  man  is  parallel  to  that  which  is  produced 
in  the  lower  animals  ;  the  fall  from  large  doses  is,  however,  less  pronounced, 
probably  because  the  cerebrum  of  man  is  proportionately  much  more 
sensitive  to  alcohol  than  is  that  of  the  animal,  and  narcosis  results  from 
smaller  doses  of  the  poison.  Again,  in  persons  accustomed  to  the  use 
of  alcohol  the  elevation  of  the  temperature  does  not  appear  ;  and,  in- 
deed, it  cannot  always  be  produced  in  a  normal  subject.  Further,  the 
habitual  use  of  alcoholic  stimulants  greatly  lessens  the  depressing  influence 
of  alcohol  upon  the  bodily  temperature,  so  that  the  temperature  of  the 
drunken  man  is  not  always  below  the  normal.  As,  however,  intoxication 
becomes  more  profound  the  tendency  to  a  fall  of  temperature  is  more  and 
more  marked. 

The  fall  of  temperature  produced  by  alcohol  is  largely  due  to  an  ex- 
cessive loss  of  heat,  but  the  relations  of  alcohol  to  thermogenesis  form 
such  an  integrant  portion  of  its  action  on  nutrition  that  its  discussion  will 
be  postponed  to  that  heading. 

Respiration. — According  to  the  experiments  of  Binz15  and  of  A. 
Jaquet,1*  small  doses  of  alcohol  increase  the  number  and  amplitude  of 
the  respiratory  movements.  The  toxic  dose  of  alcohol  decreases  the 
respiratory  air  movement.  The  drift  of  the  present  evidence  is  to  show 
that  the  action  is  centric,  and  that  alcohol  stimulates  or  paralyzes  the 
respiratory  centres  according  as  it  is  in  small  or  large  amount. 

Jaquet  certainly  failed  to  prove  the  truth  of  his  conclusion  that  the  increase  of 
respiratory  movement  produced  by  alcohol  is  due  to  local  irritation  ;  and  in  a  later 
research  Binz,  by  means  of  controlled  experiments,  apparently  demonstrated  the 
incorrectness  of  Jaquet's  theory.  Binz59  has  extended  his  experiments  not  only  to 
the  lower  animals,  but  also  to  man,  in  whom  he  found  that  the  increase  of  the 
respiration  is  distinct  although  not  very  large,  and  is  much  more  pronounced  in 
those  who  have  been  previously  fatigued. 

Relations  of  Alcohol  to  Nutrition, — In  studying  the  relations  of  alco- 
hol or  other  drugs  to  the  general  bodily  nutrition,  the  subject  naturally 
divides  itself  into  two  parts,  the  first  relating  to  the  nutrition  which  has 


CARDIAC   STIMULANTS.  295 

to  do  with  the  production  of  animal  heat  and  of  affording  force  for  the 
needs  of  the  system  ;  the  second,  that  which  has  to  do  with  the  building 
up  of  tissue  and  the  chemical  movements  of  protoplasm.  The  action  of 
a  drug  upon  heat-production  in  the  body  can  be  directly  studied  by  means 
of  proper  calorimeters,  or  it  can  be  studied  indirectly  by  chemical  exami- 
nation of  the  amount  of  oxygen  consumed  and  of  carbonic  acid  produced 
in  the  organism. 

The  first  calorimetrical  studies  upon  alcohol  were  those  by  Bevan  Lewis.15  He 
found  that  in  the  rabbit  alcohol  sometimes  produces  a  primary  lessening  of  heat- 
production,  most  marked  and  pronounced  after  small  doses,  followed  by  a  marked 
increase  in  heat-production,  most  pronounced  after  large  doses  of  the  alcohol.  In  five 
observations  by  E.  T.  Reichert  and  H.  C.  Wood  upon  dogs,  the  average  results  were 
in  accord  with  those  by  Bevan  Lewis,  although  their  individual  experiments  yielded 
somewhat  varying  results.  In  some  of  these  experiments  heat-dissipation  more  than 
kept  pace  with  the  increase  of  heat-production,  and  the  bodily  temperature  fell. 
In  other  instances  the  bodily  temperature  rose,  showing  that  heat-production  was 
increased  more  than  heat-dissipation.  In  a  further  series  of  experiments  E.  T. 
Reichert16  obtained,  in  five  experiments,  increased  heat-production,  and  in  thir- 
teen decreased  heat-production,  the  difference  not  depending  upon  dose,  and  the 
range  of  variation  of  result  being  as  much  as  sixty-five  per  cent.,  a  strong  indica- 
tion that  there  was  something  wrong  with  the  method  or  the  experiments. 

In  all  of  the  experiments  just  spoken  of  the  endeavor  was  to  discover 
the  immediate  action  of  large  doses  of  alcohol  upon  thermogenesis.  The 
results  are  somewhat  discordant  and  varying,  but  certainly  indicate  that 
alcohol  has  no  such  immediate  dominating  influence  upon  tissue  change 
as  greatly  to  increase  heat-production.  The  fall  of  bodily  temperature 
which  occurs  after  toxic  doses  of  the  drug  is  without  doubt  due  to  an 
excessive  heat-dissipation,  which  in  turn  is  the  result  of  vaso-motor  paral- 
ysis, and  the  mere  excessive  loss  of  heat  has  a  profound  influence  in  pro- 
voking increased  heat-production  just  as  increased  heat-production  has  a 
profound  influence  in  inducing  increased  heat-dissipation  ;  so  that  much 
care  is  necessary  in  the  consideration  of  calorimetrical  studies  of  large 
doses  of  vaso-motor  paralyzants.  But  if  the  action  of  alcohol  were  pro- 
nounced it  should  manifest  itself  over  all  indirect  and  disturbing  influ- 
ences. On  the  whole,  therefore,  the  earlier  calorimetrical  studies  indicate 
that  alcohol  does  not  pronouncedly  and  directly  affect  those  nutritive  pro- 
cesses through  which  the  animal  heat  is  maintained,  a  conclusion  which 
is  confirmed  in  the  very  elaborate  memoir  of  Atwater  and  Benedict,  who, 
using  small  doses  of  alcohol  in  man,  found  that  the  increased  heat-pro- 
duction was  no  greater  than  could  be  accounted  for  by  the  potential  energy 
of  the  alcohol  oxidized. 

The  effect  of  alcohol  upon  the  elimination  of  carbonic  acid  by  the 
lungs  has  been  investigated  by  several  observers,  with  different  results. 

According  to  the  researches  of  Bocker,17  of  N.  S.  Davis,18  of  Hammond,19  of 
Perrin,  *°  of  Boeck  and  Bauer,"  and  of  Rumpf,"  there  is  a  lessening  in  the  amount 
of  carbonic  acid  gas  exhaled  ;  on  the  other  hand,  E.  Smith  n  found  that  small  doses 
of  alcohol  increased  the  elimination  of  the  gas,  although  brandy,  whiskey,  and  gin 


296  GENERAL   REMEDIES. 

always  lessened  the  production.  Henrique"  found  in  himself  that  the  consump- 
tion of  oxygen  was  increased  by  alcohol.  Wolfers  K  noted  in  the  rabbit  an  increase 
both  of  the  oxygen  ingestion  and  of  the  carbonic  acid  elimination.  Bodlander 26 
found  that  in  rabbits  and  dogs  alcohol  produced  a  decrease  of  the  oxygen  consump- 
tion and  carbonic  acid  production,  whilst  in  man  Zuntz 27  obtained  an  increase  in 
carbonic  acid  production,  and  Geppert 28  no  important  effect.  The  oxidation  of  the 
alcohol  itself  must,  of  course,  yield  carbon  dioxide,  but  in  amount  too  small  to  be 
appreciable. 

In  the  older  researches  of  Boeck  and  Bauer  the  result  was  arrived  at 
that  whilst  small  doses  of  alcohol  diminish  oxygen  consumption,  large 
doses  increase  it,  and  it  is  possible  that  the  different  results  which  have 
been  obtained  by  investigators,  as  just  quoted,  may  depend  somewhat 
on  the  doses  used  by  them.  Nevertheless,  the  divergency  seems  at 
present  not  capable  of  being  cleared  up  by  such  a  supposition.  If  alcohol 
really  did  have  a  direct  powerful  influence  upon  oxidation  in  the  general 
system  the  conclusions  of  investigators  should  be  more  in  accord,  and  it 
would  seem,  therefore,  probable  that  any  influence  which  the  drug  may 
have  is  indirect,  or  is  so  feeble  as  to  be  set  aside  by  various  accidents, 
circumstances,  or  happenings  ;  possibly  even  by  other  actions  of  the  alco- 
hol itself.  This  conclusion  is  in  accord  with  that  which  has  been  reached 
calorimetrically,  and  the  best  expression  of  the  present  state  of  our  knowl- 
edge is  that  it  is  not  probable  that  alcohol  has  any  pronounced  positive  in- 
fluence upon  the  processes  of  oxidation  or  of  heat-production  in  the  system. 

The  determination  of  the  action  of  the  drug  upon  the  chemical  move- 
ments of  protoplasm,  and  the  destruction  of  albuminous  materials  in  the 
body,  is  of  course  to  be  made  by  a  study  of  its  effect  on  the  nitrogenous 
elimination. 

Among  the  earliest  students,  Bocker  is  commonly  believed  to  have  experimen- 
tally determined  that  it  lessens  the  excretion  of  urea.  We  have  seen  only  an  abstract 
of  the  original  paper  ;  in  it  this  is  not  positively  asserted,  but  seems  to  be  inferred. 
Hammond  has  performed  a  very  elaborate  series  of  experiments  upon  himself : 
first,  when  just  sufficient  food  was  taken  to  maintain  the  weight  of  the  body  ;  sec- 
ondly, when  more  than  enough  for  that  purpose  was  ingested  ;  thirdly,  when  not 
enough  was  taken.  Under  all  these  circumstances,  urea,  chlorine,  and  phosphoric 
acid  were  lessened  in  amount  by  the  ingestion  of  alcohol.  Parkes  and  Wollowicz  a 
affirm  that  their  experiments  gave  a  contrary  result.  In  examining  the  reports  of 
their  experiments  we  find,  however,  that  on  one  of  the  days  the  man  taking  the  alco- 
hol had  a  chill  followed  by  fever.  If  this  day  be  omitted,  the  average  daily  excre- 
tion of  urea  during  the  alcoholic  period  was  34.35  grammes  ;  during  the  time  when 
brandy  was  taken,  34.8  grammes ;  and  during  the  water  period,  35.02  grammes. 
The  ingestion  of  alcohol  seems,  therefore,  to  have  reduced  the  elimination  of  urea  by 
about  ten  grains  a  day.  In  the  experiments  of  L.  L.  Riess  ^  upon  two  persons  without 
analysis  of  food  or  faeces,  the  exhibition  of  alcohol  was  followed  by  great  lessening 
of  the  excretion  of  urea,  and,  to  a  less  pronounced  degree,  of  uric  acid,  chlorides, 
phosphates,  and  sulphates,  and  at  the  same  time  an  increase  of  the  bodily  weight. 
H.  Keller 31  made  experiments  upon  himself.  The  prodromic  period  was  three 
days  ;  alcohol,  one  day ;  after-period,  three  days.  The  result  was  a  fall  of  1.4 
grammes  in  nitrogen  elimination  during  the  alcohol  day,  with  an  increase  in  the 
after-period  of  one  gramme  above  the  normal.  No  examination  of  the  faeces  was 
made. 


CARDIAC  STIMULANTS.  297 

It  is  very  properly  objected  to  all  the  experiments  thus  far  quoted,  that  no  note 
was  taken  of  other  nitrogenous  elimination  than  that  through  the  kidneys.  In  1878 
Munk  M  experimented  upon  dogs  with  great  care  to  obtain  nitrogenous  equilibrium, 
using  alcohol  in  both  small  and  large  doses  and  analyzing  both  urine  and  faeces. 
The  result  arrived  at  was  that  small  doses  of  alcohol  (less  than  1.5  C.c.  absolute 
alcohol  per  kilo)  diminished  slightly  the  nitrogenous  output,  whilst  larger  doses 
(over  2  C.c. )  increased  the  elimination.  The  chief  objection  to  Munk's  experiments 
seems  to  be  the  short  time  in  which  alcohol  was  used, — three  to  five  days. 

In  experiments  made  upon  dogs  by  Charles  Norris,  Jr.,  and  E.  E.  Smith,  in 
Chittenden's  laboratory  in  Yale  University,33  the  alcohol  period  was  from  eight  to 
ten  days.  The  results  were  :  in  Experiment  No.  i,  1.9  C.c.  alcohol  per  kilo  being 
given,  the  nitrogenous  output  was  increased  two  per  cent.  ;  Experiment  No.  2,  2.3 
C.c.  per  kilo  being  given,  decrease  in  nitrogenous  elimination  somewhat  less  than 
two  per  cent.  ;  Experiment  No.  3,  2.7  C.c.  per  kilo  being  given,  decrease  about 
nine  per  cent.  Z.  Donogany  and  N.  Tibald 34  find  that  moderate  doses  of  alcohol 
increase  nitrogenous  elimination. 

In  Rosenfeld's"  experiments  nitrogenous  equilibrium  having  been  produced  in 
a  man,  alcohol  was  given  with  the  result  that  the  amount  of  nitrogen  eliminated  was 
markedly  decreased  ;  after  this  period  sugar  was  substituted  for  alcohol,  and  the 
eliminated  nitrogen  still  remained  lower  than  the  intake.  During  the  alcohol  period 
the  amount  of  uric  acid  eliminated  was  distinctly  above  the  normal ;  during  the 
sugar  period  this  was  not  the  case.  Rosenfeld  concludes  that  since  uric  acid  arises 
generally  from  the  nucleated  albumin,  the  alcohol  has  spared  the  nuclein-free 
proteid  tissues  at  the  expense  of  the  nucleo-albumins.* 

The  results  just  epitomized  are  so  varying  and  the  changes  in  the  nitro- 
genous elimination  noted  so  slow  and  inconsistent,  that  the  accounting 
for  differences  by  the  theory  of  difference  of  dose  is  not  plausible  ;  and  it 
seems  to  us  that  the  conclusion  of  Chittenden  is  correct,  that  so  far  as 
our  present  knowledge  goes  it  does  not  seem  probable  that  alcohol  has  a 
direct  specific  influence  upon  nitrogenous  elimination, — that  is,  upon  the 
chemical  movements  of  protoplasm, — a  conclusion  which,  it  should  be 
remembered,  is  corroborated  by  the  experiments  of  Stammreich  and  Miura. 

A  substance  may  very  well  have  no  specific  relation  with  tissue 
changes  and  yet  be  capable  of  acting  as  a  food  which  will  supply  force 
to  the  animal  organism.  From  the  time  of  Liebig's  celebrated  classifi- 
cation of  food  until  the  appearance  of  the  memoir  of  Lallemand,  Duroy, 
and  Perrin,  ingested  alcohol  was  almost  universally  believed  to  be  burnt 
up  in  the  body.  These  latter  observers  asserted,  however,  that  alcohol 
escapes  unchanged  from  the  body,  not  only  because  they  were  unable  to 
detect  in  the  blood  or  tissues  any  of  the  results  of  its  oxidation,  such  as 

*  S.  P.  Beebe  (A.  J.  P.,  xii,  1905)  has  established  that  alcohol  taken  without  food  causes 
no  increase  in  the  elimination  of  uric  acid  ;  that  when  it  is  taken  with  purin  food,  such  as 
meats,  it  greatly  increases  the  excretion  of  uric  acid,  the  maximum  increase  occurring  at 
the  same  time  after  a  meal  as  it  does  when  purin  food  without  alcohol  is  taken,  and  the 
purin  bases  being  affected  to  the  same  degree  as  is  the  uric  acid ;  that  when  non-purin 
food  is  taken  with  alcohol,  uric  acid  is  not  increased.  The  value  of  these  facts,  in  connec- 
tion with  the  clinical  observations  made  in  Italy  by  Dr.  W.  W.  Baldwin  (see  page  308), 
must  be  apparent.  They  at  once  confirm  and  explain  his  results.  Further,  they  show 
the  importance  of  not  exhibiting  alcohol  with  meats  in  feeble  cases  of  uric  acid  diathesis 
requiring  stimulation  ;  also  the  value  of  a  food  like  milk-punch,  which  contains  no  purin. 
base,  and  yet  is  highly  nutritious  and  stimulant. 


298  GENERAL  REMEDIES. 

aldehyde  or  acetic  acid,  but  also  because  they  found  alcohol  unchanged 
in  the  expired  air,  in  the  sweat,  and  especially  in  the  urine.  The  results 
obtained  by  the  French  investigators  were,  however,  seriously  questioned 
by  E.  Baudot,35  who  demonstrated  that  the  chromic  acid  test  which  Duroy 
and  Perrin  had  relied  on  for  detecting  alcohol  in  the  excretions  is  so 
delicate  as  to  reveal  .  165  grains  of  alcohol  in  a  quart  of  water  ;  and  found 
in  twenty  experiments  that,  except  after  immense  doses,  the  amount  of 
alcohol  eliminated  by  the  kidneys  is  so  small  as  to  amount  to  nothing. 

In  1866  Schulinus,36  showed  that  alcohol  does  not  escape  through  the  kidneys 
unless  in  very  trifling  amounts.  He  found  that  one-fourth  of  the  ingested  alcohol 
had  disappeared  from  the  body  within  three  hours,  and,  as  but  a  fractional  portion 
of  the  lost  amount  was  eliminated,  he  concluded  that  it  had  been  burnt  up.  Adolph 
Lieben :t7  and  Anstie 3i*  have  also  obtained  similar  results.  Thudichum 39  investigated 
the  matter  on  a  large  scale  in  1864,  and  again  with  the  assistance  of  Dupre"  in  1866. 
In  order  to  avoid  the  fallacies  of  the  chromic  acid  test,  the  alcohol  was  obtained 
from  the  urine  by  repeated  distillations.  In  the  first  instance  forty-four  bottles  of 
wine,  containing  four  thousand  grammes  of  alcohol,  were  drunk  by  thirty-three  men, 
out  of  whose  urine,  collected  during  the  next  six  hours,  ten  grammes,  or  only  0.25 
per  cent.,  of  the  ingested  alcohol  were  recovered.  In  the  experiments  of  1866  the 
process  was  substantially  the  same,  but,  greater  care  being  taken  to  get  absolute 
accuracy  and  to  avoid  loss  during  distillation,  0.82  per  cent,  of  the  amount  adminis- 
tered was  found  in  the  urine.  Subbotin  w  in  an  experimental  study  upon  six  rabbits, 
has  shown  that  elimination  continues  for  a  longer  time  than  had  been  generally  be- 
lieved, and  that  twice  as  much  of  the  alcohol  escapes  by  the  skin  and  lungs  as  by  the 
kidneys.  In  one  experiment  he  found  that  sixteen  per  cent,  of  the  alcohol  escaped 
unchanged  in  the  first  twenty-four  hours  ;  elimination  after  this  time,  although  per- 
ceptible, amounted  to  very  little.  As  he,  like  Lallemand  and  his  colleagues,  experi- 
mented with  poisonous  doses,  his  results  confirm  rather  than  contradict  those  of 
Baudot,  Schulinus,  Anstie,  Thudichum,  and  Dupre" ;  for  it  is  manifestly  evident  that 
after  such  doses  elimination  would  be  proportionately  greater  than  after  smaller 
quantities,  as  there  naturally  must  be  a  limit  to  the  powers  of  the  system  to  oxidize 
alcohol.  R.  D.  Edes,41  in  his  experiments,  found  that  after  small  doses  the  amount 
of  elimination  by  the  breath  is  greater  than  that  by  the  kidneys,  although  the  contrary 
holds  where  large  amounts  have  been  administered  ;  in  either  case  the  total  amount 
eliminated  was  but  a  small  percentage  of  the  amount  ingested.*  Finally,  Anstie" 
has  repeated  his  experiments,  using  the  method  of  Subbotin,  and  even  subjecting  a 
dog,  which  had  been  taking  for  some  days  very  much  larger  amounts  of  alcohol 
than  he  had  eliminated  by  skin,  kidneys,  rectum,  and  lungs,  to  distillation,  with  the 
results  of  confirming  his  first  experiments  and  of  finding  no  "residual  alcohol" 
— i.e.,  alcohol  left  in  the  body — worthy  of  mention.  In  an  elaborate  research, 
Guido  Bodlander 4S  found  that  he  himself,  after  the  use  of  alcohol  in  various  quan- 
tities, eliminated  by  the  kidneys  about  1.2  per  cent,  and  by  the  lungs  about  1.6 
per  cent.  ;  while  in  dogs  he  recovered  from  the  breath  about  2  per  cent.,  from  the 
urine  1.6  per  cent.,  and  from  the  skin  0.14  per  cent,  of  the  ingested  alcohol.  He 
failed  entirely  to  find  alcohol  in  the  intestinal  excretions,  and  also,  contrary  to 
Lewald's  observation  in  1857,  in  the  milk  of  a  goat  to  which  nearly  a  quart  of  brandy 
had  been  given.  F.  Strassman  u  found  5.21  per  cent,  eliminated  by  the  breath  and 

*  Edes  relied  upon  the  chromic  acid  test,  which  Binz  asserts  to  be  fallacious.  In  the 
experiments  made  by  Stenbach  and  Schmidt,  under  Binz's  direction,  alcohol  could  not  be 
detected  in  the  breath,  and  Binz  believes  that  no  elimination  of  it  occurs  from  the  lungs. 
He  declares  that  the  odor  of  the  breath  after  drinking  is  not  that  of  alcohol,  but  of  the 
ethers  and  other  volatile  principles  of  the  various  liquids  imbibed. 


CARDIAC   STIMULANTS.  299 

7.89  per  cent,  by  the  kidneys,  leaving  78  per  cent,  as  the  amount  destroyed  in  the 
organism.  A.  Benedicenti  *5  finds  that  an  increase  in  the  amount  of  ingested  alcohol 
does  not  greatly  influence  the  elimination  through  the  luugs,  but  that  lowered 
temperature  markedly  lessens  such  elimination.  Abelous,  Bardier  and  Ribaut60 
found  that  when  alcohol  is  given  in  from  one  to  three  c.c.  per  kilo  in  the  warm- 
blooded animals  from  eighty-seven  to  ninety  per  cent,  of  it  is  destroyed  within  eight 
hours.  In  the  frog  ninety  per  cent,  of  the  alcohol  injected  could  be  recovered  from 
the  body  under  four  days  ;  after  seven  days,  however,  none  remained  in  the  system. 
Finally,  W.  O.  Atwater  and  F.  G.  Benedict,  as  the  result  of  elaborate  studies  made 
upon  human  beings  in  a  respiratory  chamber,  found  that  when  an  amount  of  alcohol 
corresponding  to  six  ounces  of  whiskey  was  taken  the  average  elimination  was  one 
and  nine-tenths  per  cent. 

By  numerous  concurrent  investigations  *  it  seems  to  us  proven  that 
when  alcohol  is  taken  in  a  moderate  amount  it  is  not  eliminated  except 
in  very  minute  quantity,  and  is  therefore  oxidized  in  the  body.  It  has 
been  objected  to  this  that  no  one  has  as  yet  been  able  to  detect  f  in  the 
blood  any  of  the  ordinary  products  of  its  oxidation  ;  the  probable  reason 
of  this  is,  however,  that  the  oxidation  is  carried,  as  it  were,  at  one  bound 
to  its  ultimate  end,  the  production  of  water  and  of  carbonic  acid. 

A  further  confirmation  of  the  theory  that  asserts  the  oxidation  of 
alcohol  in  the  body  is  found  in  the  experiments  of  H.  Ford,48  which,  if 
accurate,  demonstrate  that  alcohol  is  formed  in  the  body  out  of  hepatic 
sugar. 

Working  on  a  very  large  scale,  by  the  distillation  of  the  blood  of  animals,  Ford 
obtained  in  weighable  quantities  a  substance  which  he  believed  to  be  alcohol.  { 
Further,  Ford  distilled  various  tissues,  also  blood  from  the  lungs  and  liver.  He  also 
made  elaborate  calculations,  based  on  the  carbon  ingested  and  on  the  carbon  ex- 
haled, as  to  the  amount  of  alcohol  which  ought  to  be  found  in  the  capillary  blood 
of  the  lungs.  The  results  are  expressed  in  the  following  table  : 

Alcohol  in  the  capillary  blood  of  the  lungs  : 

/  calculation  based  on  carbon  ingested 0.5403 

I  "       "  carbon  exhaled 0.5794 

putrescent  lung-tissue  (mean  of  exp.  8,  9,  and  n) 0.3819 

fresh  "  (     "  "    12,  13,  and  14) 0.3076 

putrescent  thoracic  blood  (mean  of  exp.  i,  2,  3,  4,  and  5)    ...  0.7625 

fresh  "  "      (mean  of  table) 0.0841 

putrescent  liver-tissue  (exp.  6) 4.3138 

fresh  (mean  of  exp.  25,  26,  and  27)     0.0190 

The  important  facts  seemingly  established  in  the  above  table  are  :  the  corre- 
spondence between  the  amount  of  alcohol  in  the  thoracic  blood  as  obtained  by 

*  We  believe  that  these  results  have  also  been  confirmed  by  Wohler  (Journal  des 
ProgrZs,  xi.),  but  we  have  not  seen  the  original  paper  or  any  abstract  of  it. 

t  Duchek  ( Vierteljahr.f.  Prakt.  Heilk.,  1853,  iii.)  did  not,  as  he  thought,  demonstrate 
the  presence  of  aldehyde  in  the  blood  of  animals  poisoned  with  alcohol. 

t  Space  is  wanting  to  describe  in  detail  the  very  elaborate  methods  employed  by 
Ford.  The  tests  which  he  relied  on,  to  prove  that  the  liquid  obtained  was  alcohol,  were 
the  chromic  acid  test,  the  peculiar  inflammability,  and  the  optical  appearance  of  the  alco- 
hol in  the  conducting-tubes  at  the  time  the  distillate  commenced  to  boil. 


300  GENERAL   REMEDIES. 

calculation  and  by  experiment ;  that  the  smallest  quantity  of  alcohol  is  to  be  ob- 
tained from  fresh  liver-tissue,  and  the  greatest  from  putrescent  liver-tissue,  in  which 
the  glycogen  must  have  undergone  fermentation.  The  fresh  thoracic  blood  was 
blood  which  had  not  traversed  the  lungs  ;  the  putrescent  thoracic  blood  of  course 
represented  the  same  blood  with  all  its  sugar  fermented. 

These  researches  of  Ford  are  certainly  corroborated  by  the  dis- 
covery, first  made,  we  believe,  by  A.  Lieben,  although  usually  attributed 
to  Dupre",47  that  a  substance  exactly  resembling  alcohol  exists  in  very 
minute  quantity  in  the  urine  even  of  teetotalers.*  M.  Be'champ,48  ap- 
parently without  a  knowledge  of  the  work  of  the  other  chemists,  obtained, 
from  the  urine  of  persons  who  had  not  taken  any  alcoholic  beverage 
for  a  long  time,  alcohol  in  sufficient  quantity  to  burn  it.  As  Lieben  also 
found  that  this  substance  exists  in  the  urine  of  dogs,  horses,  and  lions, 
and  as  A.  Rajewski49  obtained  it  from  healthy  rabbits,  and  as  further, 
Hoppe-Syler  (quoted  by  Bowditch  and  Hodge42)  states,  "traces  of  alcohol 
are  found  in  human  organisms  such  as  the  brain,  muscles,  liver,  not  only  after 
alcoholic  indulgence  but  without  this  they  seem  to  be  constantly  present, ' ' 
it  appears  to  have  been  proven  that  alcohol  is  found  in  the  normal  human 
organism,  and  probably  subserves  some  need  of  the  processes  of  the 
body,  f 

If  alcohol  be  oxidized  in  the  body,  it  must  of  course  generate  force, 
measurable  by  the  modern  standard  of  the  heat-unit.  A  little  calcula- 
tion will  show  the  importance,  or  rather  the  great  amount,  of  the  gen- 
erated force.  According  to  Duprg,50  one  gramme  of  alcohol  oxidized 
in  the  body  evolves  7184  units  of  heat,  while  the  same  weight  of  lean 
beef  gives  off  only  1482  units  of  heat.  It  has  been  estimated  that  9.3 
ounces  of  lean  beef — equal  to  about  two  ounces  of  alcohol — will  supply 
the  necessary  force  to  maintain  the  circulation  and  respiration  of  an  aver- 
age man  for  one  day.  That  is,  four  ounces  of  strong  spirit  will  suffice 
for  this  purpose. 

The  ergographic  studies  made  by  Lombard,  Kraepelin,  Scheffer,  and 
other  investigators,  afford  no  proof  that  alcohol  in  moderate  dose  has  a 
direct  action  upon  the  working  power  of  the  muscle.  An  underlying, 
almost  unsurmountable  difficulty  in  this  method  of  experimentation  is  the 
impossibility  of  separating  the  indirect  from  the  direct  effects  of  alcohol. 
The  experiments  which  have  been  made  with  the  isolated  frog's  muscle 
indicate  that  alcohol  has,  when  in  appropriate  dose,  a  direct  stimulant 
effect  either  upon  the  intra-muscular  nerve-endings  or  the  sarcolemma. 

*  It  has  been  asserted  that  the  substance  "  is  not  alcohol.  It  passes  over  among  the 
earliest  products  of  distillation,  yields  acetic  acid  on  being  oxidized,  reduces  the  potas- 
sium bichromate  when  dilute  sulphuric  acid  is  present,  and  its  aqueous  solution  has  a 
lower  density  than  water.  It  furnishes  iodoform,  and  exists  in  the  urine  in  a  very  small 
quantity."  Possessing  the  physical  and  chemical  characters  of  alcohol,  to  ordinary 
minds  it  is  alcohol. 

t  Doming  and  Praetorius  found  that  fecal  matter  on  decomposition  yielded  alcohol  to 
such  an  extent  as  to  suggest  a  possible  remunerative  source.  Von  Meyer  and  O.  Mohr, 
working  independently,  found  that  the  amount  of  alcohol  in  the  fecal  matter  was  too 
small  for  commercial  product  (Oiem.  Centralb.,  1.  1904,  636). 


CARDIAC  STIMULANTS.  301 

Further,  when  there  is  a  lack  of  sufficient  food,  alcohol  seems  to  be  espe- 
cially useful  for  the  purpose  of  increasing  muscular  power  and  probably  is 
used  by  the  muscle  as  power-source.  Large  doses  of  alcohol  depress  the 
muscle:  apparently  its  action  upon  voluntary  muscle  is  very  similar  to  its 
influence  upon  the  heart-muscle. 

Lombard  Warren  •*  found  that  small  doses  of  alcohol  increased,  larger  doses 
diminished,  his  muscular  power.  Dastre  *•  found  that  alcohol  first  temporarily  in- 
creased, afterwards  depressed,  the  muscle,  so  that  the  whole  muscular  work  done 
when  under  its  influence  was  less  than  normal.  In  H.  Prey's51  studies  the  alcohol 
lessened  the  working  power  of  the  normal  muscle,  but  markedly  refreshed  the 
nearly  exhausted  muscle,  a  refreshment  which  Frey  believes  to  be  due  to  the  alcohol 
supplying  an  oxidizable  material  to  the  muscle  which  had  exhausted  its  stored-up 
force-producing  material.  Scheffer  w  reached  the  conclusion  that  alcohol  at  first 
increases  the  muscular  working  power  and  shortly  afterwards  diminishes  it. 
Schnyder  determined  that  alcohol  in  small  quantities,  taken  by  the  individual  when 
tired  and  in  a  fasting  condition,  exerts  a  favorable  influence  upon  the  force  of  the 
muscles ;  an  influence,  however,  which  is  less  than  that  of  ordinary  food  of  equal 
caloric  value  ;  also,  further,  that  when  there  is  an  abundance  of  food,  alcohol  fails 
to  make  itself  manifest ;  and  in  any  case  if  in  large  amount,  by  its  action  upon 
the  nervous  system  depresses  muscular  force.  F.  S.  Lee  and  W.  Salant M  found 
that  dilute  alcohol,  about  forty  parts  by  weight  to  one  thousand  of  the  frog,  quick- 
ened both  contraction  and  relaxation,  delayed  fatigue,  and  increased  the  amount  of 
work  possible  to  the  isolated  muscle. 

These  considerations  warrant  the  statement  that  in  a  certain  sense  alco- 
hol is  a  food, — i.  e. ,  that  it  is  capable  of  being  used  for  the  purposes  of  the 
organism;  but  it  does  not  necessarily  follow  from  this  that  alcohol  is 
capable  of  replacing  fats  and  hydrocarbons  in  food.  In  attempting  the 
determination  of  this,  two  methods  have  been  used, — that  of  Von  Noor- 
den  and  that  of  Atwater. 

According  to  the  Method  of  Von  Noorden  the  individual  is  brought  into  a  con- 
dition of  nitrogenous  equilibrium  by  careful  feeding,  and  when  this  condition  has 
been  thoroughly  established,  non-nitrogenous  articles  of  food  are  withdrawn  and 
alcohol  substituted  in  isodynamic  quantity.  Under  such  circumstances,  if  the  alco- 
hol be  superior  to  the  hydrocarbon  in  replacing  the  nitrogenous  material,  less  nitro- 
gen should  be  eliminated  than  before  its  administration  ;  if  the  power  of  the  alcohol 
be  less  than  that  of  the  hydrocarbon,  more  nitrogen  would  be  thrown  off ;  if  the 
alcohol  just  replaced  the  hydrocarbon,  the  nitrogenous  equilibrium  would  not  be 
disturbed. 

Stammreich's 52  experiments  upon  himself  were  two  in  number.  In  the  first 
experiment  there  was  a  distinct  lessening  of  the  elimination  of  nitrogen  during  the 
alcohol  period,  showing  that  the  alcohol  replaced  the  nitrogenous  material  more 
actively  than  the  corresponding  fat  mass  for  which  it  had  been  substituted.  In  the 
second  experiment,  with  a  lessened  amount  of  nitrogen  in  the  food,  there  was  at 
first  no  pronounced  change  in  the  nitrogenous  elimination,  followed,  however,  after 
two  days  by  a  marked  increase,  which  continued  for  three  days  after  the  withdrawal 
of  the  alcohol.  A  third  set  of  experiments  were  made  with  very  little  nitrogen  in 
the  food.  Under  these  circumstances  there  was  a  great  increase  of  the  elimination 
of  nitrogen  during  the  alcohol  period. 

As  the  result  of  the  comparison  of  these  various  experiments  Von  Noorden 
reached  the  conclusion  that  when  the  food  is  rich  in  albuminous  compounds,  alco- 


302  GENERAL  REMEDIES. 

hoi  is  able  to  replace  hydrocarbon  or  fats  ;  but  when  the  food  is  poor  in  albumin, 
it  cannot  do  so.  A  similar  series  of  experiments  have  been  made  by  K.  Miura.M 
In  the  experiments — in  which  food  with  but  little  nitrogen  was  given — the  results  ob- 
tained by  Miura  were  similar  to  those  of  Stammreich.  On  the  other  hand,  in  oppo- 
sition to  Stammreich,  Miura  found  that  when  the  food  is  rich  in  albuminous  material, 
alcohol  is  not  able  to  replace  the  non-nitrogenous  foods.  Miura  believes  that  these 
differences  depend  in  part  upon  the  facts  that  in  Stammreich' s  experiments  the  alco- 
hol was  substituted  for  fats,  whilst  in  his  experiments  it  replaced  hydrocarbons,  which, 
according  to  Voit,  have  greater  power  of  sparing  the  nitrogen  materials  than  have 
the  fats  ;  so  that  alcohol  might  be  equivalent  to  fats  and  yet  not  to  hydrocarbons. 
Neumann,68  after  producing  in  himself  nitrogenous  equilibrium,  omitted  half  of  the 
fat  from  his  diet,  causing  thereby  nitrogenous  loss.  By  substituting  alcohol  for  the 
fat  he  found  that  there  was  a  return  to  nitrogenous  equilibrium.  In  a  subsequent 
period,  after  re-establishment  of  nitrogenous  equilibrium,  he  added  alcohol  in  doses 
increasing  up  to  one  hundred  grammes  a  day,  with  pronounced  nitrogenous  gain. 
In  a  third  period,  the  alcohol  was  continued,  but  a  part  of  the  fat  was  withdrawn, 
which  caused  a  slight  nitrogenous  balance.  From  these  experiments  Neumann 
concludes  that  alcohol  has  the  property  of  sparing  the  proteids,  but  is  probably  not 
capable  of  entirely  replacing  the  fats. 

In  the  extraordinarily  elaborate  research  made  by  W.  O.  Atwater  and  F.  G. 
Benedict,67  *  three  selectee,  men  were  kept  for  periods  varying  from  five  to  nine  days 
in  a  respiration  calorimeter,  «;  *uch  a  way  that  the  heat-production  and  all  the  excre- 
tions from  the  body,  liquid  and  solid,  could  be  studied.  On  some  days  no  exercise 
was  taken  ;  on  others  by  means  of  a  stationary  bicycle,  a  large  amount  of  measured 
work  was  done.  The  diet  was  regulated  with  scientific  accuracy.  On  the  alcoholic 
day  one  gramme  per  kilogramme  of  bodily  weight  of  alcohol  was  taken  in  six  doses  ; 
a  quantity  of  alcohol  which  seems  small  but  whose  potential  energy  was  about  one- 
fifth  of  the  total  diet  energy  in  the  rest-period,  and  one-seventh  of  the  total  diet 
energy  in  the  work-period.  It  was  determined  in  these  experiments  that  the  poten- 
tial energy  of  the  alcohol  was  transformed  by  the  body  into  kinetic  energy  as  com- 
pletely as  was  that  of  the  ordinary  nutrients  ;  also  that  the  efficiency  of  alcohol  in 
the  protection  of  body-fat  was  equal  to  that  of  the  corresponding  non-alcoholic 
diet ;  alcohol,  isodynamic  amounts  of  fats  and  other  carbohydrates  having,  there- 
fore, equal  protective  power  against  loss  of  fat  The  efficiency  of  the  alcohol  in 
protecting  the  protein  of  the  body  was  evident  but  usually  not  entirely  equal  to  that 
of  isodynamic  amounts  of  ordinary  nutrients,  although  in  some  of  the  experiments 
alcohol  seemed  to  protect  protein  equally  with  ordinary  food. 

In  regard  to  muscular  work,  the  experiments  seem  to  show  that  the  total  energy 
of  the  ordinary  diet  is  utilized  a  little  more  thoroughly  than  is  that  of  alcohol, 
but  the  difference  was  so  small  as  to  be  entirely  within  the  limits  of  experimental 
error ;  it,  on  the  average,  was  less  than  one  per  cent,  of  total  energy,  and  is, 
therefore,  of  very  little  importance. 

It  is  proven  that  alcohol  when  taken  in  moderate  amount  is  oxidized 
in  the  body,  and  in  this  process  of  oxidation  it  must  yield  kinetic  or  active 
energy.  The  researches  which  have  just  been  epitomized  seem  to  us  to 
definitely  determine  that  this  kinetic  or  active  energy  is  employed  by 
the  organism  for  life  purposes,  and  that  alcohol  must  be  considered  as  a 

*  The  research  of  Atwater  and  Benedict  deserves  much  more  thorough  discussion 
than  can  be  given  in  the  text  of  this  book.  It  seems  to  us  most  remarkable  in  conception 
and  execution,  and  for  the  present  at  least  these  results  ought  to  be  taken  as  conclusive. 
The  method  employed  in  its  directness  is  in  our  thinking  far  more  likely  to  yield  the  truth 
than  is  the  indirect  plan  of  producing  nitrogenous  equilibrium.  The  number  and  extent 
of  the  experiments  also  are  out  of  comparison  with  those  of  the  early  workers. 


CARDIAC   STIMULANTS.  303 

food  capable  to  some  extent  of  replacing  hydrocarbons.  It  must  be  remem- 
bered in  applying  this  scientific  knowledge,  however,  that  the  organism 
can  only  consume  a  limited  amount  of  alcohol,  and  that,  therefore,  the 
food  value  of  alcohol  has  narrow  limitations. 

Digestion. — It  is  definitely  proven  that  alcohol  when  in  small  amount 
outside  of  the  body  does  not  retard  the  digestive  power  either  of  ptyalin 
or  of  the  gastric  juice,  seeming  rather  to  increase  than  to  diminish 
activity. 

The  laboratory  researches  of  W.  Buchner,*4  R.  H.  Chittenden  and  L.  B.  Men- 
del,45 and  of  William  Roberts  are  concordant  and  conclusive.  The  results  reached 
are  as  follows :  Salivary  digestion  is  not  very  actively  affected  by  the  presence  of 
pure  alcohol ;  indeed,  when  there  is  not  more  than  four  or  five  per  cent,  the  diges- 
tive power  of  ptyalin  seems  to  be  increased :  ten  per  cent,  of  absolute  alcohol 
(*'.  e.,  twenty  per  cent  of  proof -spirit)  retards  it  slowly.  On  the  other  hand,  wines 
and  malt  liquors  very  greatly  hamper  salivary  digestion  almost  in  exact  proportion 
to  their  degree  of  acidity.  Pure  alcohol  seems  to  increase  rather  than  diminish 
gastric-juice  digestion  until  the  amount  rises  to  two  or  three  per  cent.  ;  less  than 
ten  per  cent,  appears  not  to  be  constantly  and  demonstrably  inhibitive  ;  after  twenty 
per  cent,  the  digestive  action  may  be  reduced  to  one-third.  A  very  important  fact 
is  that  the  retardation  produced  by  a  given  percentage  of  alcohol  varies  greatly  with 
the  activity  of  the  ferment  and  the  nature  of  the  material  to  be  digested.  Chitten- 
den and  Mendel  have  found  that  three  per  cent,  of  alcohol  distinctly  retards  the 
proteolytic  action  of  the  pancreatic  juice,  whilst,  according  to  A.  Dastre,5*  fifteen 
per  cent,  puts  an  end  to  the  artificial  pancreatic  digestion  of  nitrogenous  materials. 

It  is  evident  that  a  drug  may  delay  artificial  digestion,  and  yet,  in 
the  living  animal,  by  provoking  secretion,  by  increasing  peristaltic  activity, 
or  in  other  ways  it  may  really  stimulate  natural  digestion.  The  experience 
of  every  ' '  diner-out ' '  teaches  him  that  a  moderate  amount  of  alcoholic 
drink  taken  during  the  dinner  increases  his  digestive  power  ;  and  the 
experimental  evidence  corroborates  this  experience  ;  as  it  does  also  the 
well-known  fact  that  some  wines  interfere  with  digestion,  in  some  way 
not  at  all  dependent  upon  the  alcohol  which  they  contain. 

Chittenden,  Mendel,  and  Jackson57  found  that  alcohol  temporarily  increases  the 
flow  of  saliva  reflexly  by  its  irritant  influence  upon  the  mucous  membranes  of  the 
mouth  ;  and  that  it  increases  the  secretion  of  gastric  juice  very  greatly,  the  action 
on  the  stomach  being  exerted  not  only  by  alcoholic  fluids  in  the  stomach  but  by 
absorbed  alcohol.  They  further  determined  that  the  ordinary  alcoholic  drinks  agree 
in  stimulating  gastric  secretion,  and  that  the  gastric  juice  secreted  was  stronger  in 
hydrochloric  acid  and  in  proteolytic  power  than  normal.  It  is  worthy  of  note  that 
in  experiments  made  by  Chittenden  upon  healthy  dogs  with  gastric  fistulas,  using 
proteid  test-meals,  digestion  was  never  retarded  nor  accelerated,  leading  to  the 
conclusion  that  in  those  cases  there  was  a  practical  balance  between  the  two  antag- 
onistic actions  of  alcohol  upon  the  digestion. 

Radzikowski n  experimentally  determined  that  when  alcohol  is  taken  into  the 
stomach  in  small  amount  it  increases  the  secretion  of  gastric  juice,  and  also  its 
contained  acid  and  pepsin.  In  confirmation  of  this,  Spiro  *  found  that  an  enemata 
of  from  seven  to  ten  c.c.  of  alcohol  causes  in  man  a  free  secretion  of  a  very  acid 
gastric  juice  in  the  empty  stomach,  an  effect  which  is  probably  due  to  an  excretion 
of  alcohol  into  the  stomach,  since  M.  N.  Grehant™  has  proven  that  when  alcohol 


304  GENERAL  REMEDIES. 

is  injected  into  the  blood  it  is  excreted  into  the  stomach.  Storck T6  finds  that  the 
digestion  of  starch  within  the  mouth  is  increased  by  the  local  action  of  preparations 
of  alcohol  of  the  strength  of  from  two  to  five  per  cent.,  but  delayed  by  stronger 
preparations. 

SUMMARY. — Alcohol  in  small  doses  acts  as  a  stimulant  to  the  gan- 
glionic  cells  of  the  cerebrum,  and  perhaps  also  to  the  motor  tract  of  the 
spinal  cord.  In  large  amount  it  certainly  is  a  depressant  to  the  cerebral 
and  spinal  ganglionic  cells,  as  -well  as  the  nerve-trunks.  The  action  of 
small  doses  upon  the  respiratory  centres  is  not  thoroughly  established, 
but  is  probably  stimulant;  large  doses  depress  the  respiratory  centres, 
and  finally  may  cause  death  by  centric  paralytic  asphyxia.  Upon  the 
heart  the  small  dose  of  alcohol  acts  as  a  direct  stimulant,  the  large  dose 
as  a  depressant  or  paralyzant.  The  influence  of  minute  doses  upon  the 
vaso-motor  system  is  not  thoroughly  -worked  out,  but  there  appears  to 
be  a  -widening  of  the  blood-paths  at  a  time  -when  the  heart  is  still  stim- 
ulated, so  that  there  is  a  marked  quickening  of  the  blood-movement. 
The  toxic  dose  of  alcohol  paralyzes  the  blood-vessels,  probably  both 
centrally  and  peripherally.  The  peripheral  temperature  is  often  in- 
creased by  small  amounts  of  alcohol,  and  there  may  be  even  a  slight 
increase  in  the  central  temperature,  probably  caused  by  quickening  of 
the  circulation ;  the  large  dose  of  alcohol  lowers  the  animal  tempera- 
ture, probably  by  causing  vaso-motor  paralysis,  and  thereby  increasing 
heat-dissipation. 

In  regard  to  the  effect  of  alcohol  upon  the  nutrition  there  is  much 
contradictory  evidence,  but  the  present  probabilities  are  that  the  drug 
has  no  specific  influence  upon  the  production  of  heat  or  of  carbonic 
acid,  or  upon  nitrogenous  elimination,  and  that  therefore  it  has  little  or 
no  direct  effect  upon  the  nutrition,  unless  it  be  in  poisonous  doses,  -when 
it  certainly  disturbs  all  nutritive  processes.  After  absorption  into  the 
blood,  alcohol  is  to  a  limited  extent  eliminated  through  the  lungs,  the 
skin,  and  the  kidneys  unchanged,  but  is  largely,  and  -when  in  small 
amount  practically  -wholly,  burnt  up  in  the  system.  In  its  destruction 
it  yields  kinetic  energy  -which  is  employed  by  the  organism  for  its  pur- 
poses so  that  it  (alcohol)  is  capable  to  a  considerable  extent  of  re- 
placing the  hydrocarbons  of  ordinary  food,  and  must  be  considered  to 
have  definite  food  value. 

THERAPEUTICS. — Our  knowledge  of  the  physiological  properties  of 
alcohol  shows  that  its  chief  therapeutic  value  in  acute  disease  is  as  a 
stimulant,  a  temporary  imparter  of  power  which  will  enable  the  system 
to  stand  some  strain  of  short  duration, — to  bridge  over  some  period  of 
weakness. 

The  cases  to  which  it  is  especially  adapted  may  be  divided  into  three 
classes  : 

First.  Those  in  which  there  is  a  temporary  loss  of  heart-power,  as 
in  fainting  from  exhaustion,  loss  of  blood,  or  other  cause.  In  these 
cases  the  alcoholic  stimulant  should,  if  possible,  be  given  hot,  and  not 
much  diluted  ;  with  it  should  also  be  exhibited  some  more  rapidly  acting 
diffusible  stimulant,  such  as  ammonia. 

Second.  Those  acute  diseases  in  which  the  powers  of  the  system  are 
in  danger  of  being  used  up  ;  to  aid  in  the  digestion  of  food  and  in  the 


CARDIAC   STIMULANTS.  305 

maintenance  of  power.  Alcohol,  as  has  already  been  stated,  is  to  a  cer- 
tain extent  a  food,  but  it  will  not  of  itself  sustain  life  for  a  long  time, 
and  should  in  adynamic  disease  always,  unless  for  special  reasons,  be 
combined  with  milk,  or  occasionally  with  eggs.  One  great  source  of 
its  value  in  these  diseases  is  the  power  it  imparts  of  assimilating  food, 
and  in  milk  punch  are  furnished  the  stimulant  to  digestion  and  the  most 
perfect  food  known  for  digestion.  This  use  of  alcohol  is  apart  from  its 
office  in  the  lowest  stage  of  fever  as  a  heart-  and  nerve- stimulant. 
Employed  for  this  purpose  it  is  useful  in  all  stages  of  the  adynamic 
fevers,  such  as  typhus  and  typhoid*  By  the  exhibition  of  three  or  four 
ounces  of  milk  every  two  hours,  with  one  or  two  drachms  of  brandy 
or  whiskey,  from  the  beginning  of  the  attack,  in  many  cases  the  develop- 
ment of  the  severe  adynamic  symptoms  may  be  prevented. 

A.  Ott62  claims  to  have  experimentally  determined  upon  a  fever  patient  that 
the  value  of  alcohol  as  an  albumen-saving  food  is  equal  to  its  isodynamic  equivalent 
of  a  pure  food  hydrocarbon. 

In  the  advanced  stages  of  pneumonia,  pytzmia,  exanthematous  fever, 
and  other  acute  diseases,  when  the  typhoid  state  is  well  developed,  alcohol 
should  be  given  boldly,  to  quiet  by  stimulation  the  nervous  and  circu- 
latory systems,  to  afford  a  food  which  will  in  a  measure  replace  the 
natural  pabulum,  to  aid  in  the  digestion  of  milk  and  other  simple  nourish- 
ment, to  aid  in  lowering  temperature  :  in  a  word,  to  enable  the  system  to 
stand  the  drain  upon  its  vital  powers,  and  at  the  same  time  to  check  such 
drain. 

Although  a  great  deal  of  work  has  been  done  upon  the  subject,  the 
question  as  to  whether  alcohol  does  or  does  not,  when  given  in  moderate 
dose,  increase  the  resisting  power  of  the  system  to  infectious  diseases  can- 
not be  at  present  answered  with  positiveness. 

Binz78  found  that  alcohol  increases  the  resistive  power  of  the  dog  to  septic 
material,  but  his  experiments  seem  to  have  been  too  few  to  be  of  value.  In  an  in- 
complete research,  H.  A.  Hare  and  M.  E.  Pennington79  found  that  alcohol  increases 
the  bactericidal  property  of  the  blood  at  least  against  some  pathogenic  organ- 
isms. Gruber80  affirms,  as  the  result  of  experimentation,  that  the  frequent  admin- 
istration of  small  doses  of  alcohol  to  guinea  pigs,  injected  with  bacillus  prodigiosus, 
prolonged  life,  and  in  some  instances  even  brought  about  restoration.  Opposed  to 
these  results  are  those  of  various  investigators.  Doyen  and  Thomas gl  both  found  that 
alcohol  increases  the  liability  of  animals  to  infection  with  cholera.  Abbott,82  using 
streptococcus  pyogenes,  bacillus  coli,  or  staphylococcus  pyogenes  aureus,  found 
that  the  alcoholized  animals  died  with  much  more  certainty  than  did  those  of  the 
control  experiments  in  which  no  alcohol  was  given.  Dele"arde 8S  reached  the  result 
that  alcohol  destroys  the  immunization  of  rabbits  against  tetanus  and  anthrax. 
Laitinen,84  in  a  very  elaborate  research  upon  three  hundred  and  forty-two  animals, 
representing  six  species  of  mammals  and  birds,  using  anthrax,  tubercle  bacilli,  and 
diphtheria  toxin,  arrived  at  the  conclusion  that  alcohol  diminishes  very  distinctly 

*  The  statement  of  J.  H.  Kellogg  (Journ.  Amer.  Med.  Assoc.,  1895,  xxv.),  that  the 
administration  of  brandy  markedly  lessens  the  toxicity  of  the  urine  in  typhoid  fever, 
suggests  a  very  important  line  of  research. 


306  GENERAL  REMEDIES. 

the  resistance  of  the  body  towards  infectious  diseases.  Pawlowsky K  found  that 
alcoholized  animals  reacted  much  more  freely  to  staphylococcus  citreus  than  did 
the  normal  animal.  Gruber  and  Koegler  M  determined  that  alcoholization  increases 
the  mortality  of  animals  infected  with  the  pneumobacillus.  Goldberg 87  came  to  a 
similar  conclusion  in  regard  to  the  influence  of  anthrax  on  pigeons.  Ausems M 
found  that  the  administration  of  alcohol  in  small  doses  to  rabbits  before  infection 
diminished  their  resistance. 

At  first  sight  the  experimental  evidence  which  has  just  been  epito- 
mized would  seem  sufficient  to  determine  that  alcohol  diminishes  rather 
than  increases  the  power  of  the  system  to  resist  various  infections,  and  also 
puts  aside  immunization.  Undoubtedly,  however,  as  clearly  pointed  out  by 
S.  J.  Meltzer,  the  doses  of  alcohol  which  have  been  used  by  experimenters 
have  been  toxic  and  not  therapeutic,  so  that  the  importance  of  the  re- 
searches is  largely  invalidated.  Moreover,  in  most  cases  the  alcohol  has 
been  given  through  the  stomach-tube,  with,  as  insisted  upon  by  Abbott, 
resulting  erosion  and  gastric  inflammation  distinctly  complicating  the 
bodily  condition  of  the  animal. 

Properly  administered,  alcohol  always  promotes,  not  arrests,  secretion 
in  fever  cases.  The  guide  to  the  amount  given  should  be  the  effects  pro- 
duced ;  so  long  as  the  drug  lowers  temperature  and  pulse-rate,  moistens 
the  dry  tongue  and  skin,  and  quiets  the  nervous  disturbance,  it  does  good  ; 
if,  however,  the  tongue  grows  dryer,  the  pulse  puts  on  an  angry,  bounding 
character,  and  the  patient  becomes  restless  and  uneasy,  stimulation  is 
being  pushed  too  far,  and  the  amount  exhibited  should  be  lessened. 
Whenever  the  odor  of  liquor  appears  upon  the  breath,  the  patient  is  almost 
certainly  taking  too  much. 

The  antipyretic  action  of  alcohol  has  suggested  its  use  in  cases  of 
high  temperature  ;  as,  however,  this  is  only  one  of  its  actions,  and  is 
not  decided  unless  very  large  doses  be  given,  alcohol  cannot  be  em- 
ployed as  a  general  febrifuge.  True  arterial  excitement  and  sthenic 
inflammation  certainly  contra-indicate  its  use.  The  rule  may  be  laid 
down  as  follows  :  high  temperature  is  an  indication  for  the  use  of  alcohol 
only  when  other  symptoms  also  demand  it ;  in  itself  high  temperature  is 
never  a  centra-indication  to  alcohol.  In  acute  sthenic  diseases,  after  the 
progressive  stage  has  passed  and  the  results  of  the  disease  simply  remain 
to  be  overcome,  alcohol  and  milk  will  often  save  life.  Thus,  in  acute 
pneumonia,  when  so  much  consolidation  has  occurred  as  to  render  it 
doubtful  whether  the  exuded  matter  can  be  removed,  or  in  abscess, 
when  large  amounts  of  pus  have  formed,  the  demand  may  be  urgent  for 
alcohol  as  a  food  and  as  an  aider  of  digestion,  and  sometimes  as  a 
stimulant. 

Third.  Those  cases  in  which  there  is  a  depressing  agent  present.  In 
many  forms  of  poisoning  alcohol  may  be  used  with  signal  advantage 
simply  as  an  arterial  and  nervous  stimulant,  to  overcome  the  influence  of 
a  depressing  agent.  Thus,  when  death  is  threatened  from  cardiac  failure 
in  poisoning  by  toxines,  venom,  veratrum  viride,  aconite,  or  similarly  acting 
toxic  agents,  whether  of  animal  or  of  vegetable  origin,  alcohol  is  an  im- 


CARDIAC   STIMULANTS.  307 

portant  remedy,  unless  the  poison,  as  in  the  case  of  an  anaesthetic,  is 
physiologically  so  closely  allied  to  alcohol  that  the  small  dose  of  alcohol 
becomes  a  reinforcing  depressant.  In  acute  depression  threatening  a  fatal 
issue  it  should  be  administered  freely,  not  much  diluted,  and,  if  conven- 
ient, hot.  From  one  to  four  ounces  of  whiskey  should  be  given,  repeated 
every  ten  or  fifteen  minutes,  until  slight  intoxication,  convalescence,  or 
death  has  resulted. 

What  has  been  said  up  to  this  point  in  regard  to  the  therapeutic  action 
of  alcohol  has  had  reference  to  acute  disease.  The  value  of  the  drug  in 
some  chronic  diseases  cannot  be  doubted  ;  but  in  prescribing  it  the  phy- 
sician should  never  lose  sight  of  the  possible  danger  of  producing  a  habit 
far  worse  in  its  fruits  than  is  death  itself. 

In  chronic  neuralgia,  in  hypochondriasis ,  and  in  melancholia  temporary 
relief  may  sometimes  be^  obtained  by  the  use  of  stimulants  ;  but  the  very 
relief  afforded  doubles  the  temptation  to  the  frequent  use  of  the  alcohol, 
and,  as  the  system  becomes  habituated  to  its  action  and  the  dose  has  to 
be  more  and  more  increased,  the  habit  of  frequent  stimulation  grows  al- 
most of  necessity  into  drunkenness.  For  this  reason  we  do  not  think  that 
the  physician  is  ever  justified  in  prescribing  alcohol  for  its  narcotic  stimu- 
lant effect  in  these  cases.  The  chief  legitimate  uses  of  alcohol  in  chronic 
diseases  are  to  aid  in  digestion,  to  furnish  a  food  which,  without  any 
digestive  effort  upon  the  part  of  the  system,  shall  be  absorbed  and  shall 
take  the  place  of  more  ordinary  food,  and  to  check  excessive  tissue-waste. 
Of  course  these  indications  exist  only  in  such  diseases  as  are  either  de- 
pendent upon  or  closely  associated  with  a  condition  of  the  system  in  which 
the  general  nutrition  is  depraved.  In  purely  local  affections  the  use  of 
alcohol  is  rarely  called  for  except  in  the  last  moments  of  life,  when  it  may 
always  be  employed  to  afford  relief  and  to  protract  for  a  short  time  the 
struggle.  In  chronic  dyspepsia,  alcohol  administered  with  the  food  often 
aids  very  materially  in  the  assimilation  of  the  latter  ;  but  care  should  be 
exercised  in  prescribing .  it,  for  the  same  reasons  as  were  given  a  mo- 
ment since  when  speaking  of  the  use  of  stimulants  in  melancholia.  In 
many  cases  of  chronic  neuralgia,  not  as  a  narcotic  stimulant,  but  as  a 
food  and  a  stimulant  to  nutrition,  alcohol  is  often  of  service.  The  danger 
of  establishing  a  fatal  habit  in  this  disease  is,  however,  excessive.  In 
almost  all  cases  in  which  alcohol  is  called  for  in  neuralgia,  cod-liver  oil  is 
also  indicated,  and  it  is  generally  best  to  exhibit  the  two  remedies  to- 
gether, so  as  to  obtain  the  easy  assimilation  of  the  oil  and  to  guard  against 
evil  moral  results. 

In  phthisis  and  its  congener  scrofulosis,  there  can  be  no  doubt  as  to 
the  great  value  of  alcohol  ;  and  in  the  latter  stages  of  consumption  its 
judicious  use  as  an  antipyretic  narcotic  stimulant  to  lessen  the  sufferings 
of  the  patient  is  perfectly  justifiable.  During  the  earlier  chronic  move- 
ments of  the  affection,  alcohol  taken  with  cod-liver  oil,  or  in  small  amounts 
with  the  food  at  meal-times,  conduces  not  so  much  to  the  comfort  as  to 
the  well-being  and  recovery  of  the  patient. 


308  GENERAL  REMEDIES. 

The  question  as  to  the  propriety  of  the  daily  use  of  alcohol  by 
healthy  men  is  at  present  a  very  serious  one,  involving  so  many  moral 
and  politico-moral  issues  that  it  cannot  be  fully  discussed  here.  Suffice 
it  to  state,  as  obvious  inferences  from  our  present  knowledge  of  the 
physiological  action  of  alcohol,  that  the  habitual  use  of  moderate  amounts 
of  alcohol  does  not  directly  and  of  necessity  do  harm  ;  that  to  a  certain 
extent  it  is  capable  of  replacing  ordinary  food,  so  that  if  the  latter  be 
scanty,  or  even  if  it  be  coarse  and  not  easily  digested,  alcohol,  in  some 
form  or  other,  is  of  great  advantage  ;  that  in  all  cases  it  should  be  taken 
well  diluted,  so  as  not  to  irritate  the  stomach  ;  and  that  wine  or  malt 
liquors  are  certainly  preferable  to  spirits.  When,  as  is  almost  universally 
the  case  in  the  United  States,  food  is  habitually  taken  in  larger  quantity 
than  is  required  for  the  system,  then  the  habitual  use  of  alcohol  dis- 
tinctly is  injurious,  increasing  the  probabilities  of  plethora  and  lithaemia. 

We  are  indebted  to  Dr.  W.  W.  Baldwin,  of  Rome,  for  a  very  striking  illustra- 
tion of  this  matter.  When  the  Norwich  Union  Life  Insurance  Company  of  England 
opened  its  offices  in  Italy,  it  was  soon  found  that  the  alcoholic  habits  of  the  people 
of  Italy  were  such  that  if  the  alcoholic  limitations  used  by  the  company  were  ad- 
hered to  practically  no  business  could  be  obtained.  Dr.  W.  W.  Baldwin,  a  very 
active  practitioner  for  a  number  of  years  in  Italy,  was  instructed  by  the  Company 
to  report  upon  the  subject.  According  to  his  unpublished  report,  it  is  the  habit  of 
the  lower  and  middle  classes  of  Italy  to  take  for  each  of  the  three  daily  meals  a 
quart  bottle  or  more  of  wine  with  a  large  dish  of  macaroni ;  animal  food  entering 
but  scarcely  into  the  dietary  list.  Under  these  circumstances  physical  strength  is 
preserved,  and  although  the  wine  of  Italy  compared  with  that  of  the  North  is  strong 
in  alcohol,  no  evidences  of  alcoholism,  and  no  gouty  degenerations  or  diseases 
appear  ;  gout,  in  fact,  in  the  Doctor's  experience,  being  an  almost  unknown  thing 
among  the  lower  and  middle  classes  of  Italy.  On  the  other  hand,  when  an  Anglo- 
Saxon,  German,  or  any  other  Northerner  settles  in  Italy  and  adopts  the  wine  habits 
of  the  Italians,  maintaining  his  own  eating  habits,  severe  gouty  degenerations 
(especially  of  the  viscera)  or  other  alcoholic  changes  very  commonly  appear  after 
one  or  two  years. 

The  experience  of  Arctic  explorers  has  clearly  shown  that  alcohol 
has  no  heat-producing  power,  so  that  at  a  time  when  it  was  believed 
by  physiologists  to  have  such  influence  the  Northern  navigators  had 
learned  that  the  free  use  of  spirits,  far  from  enabling  a  man  to  with- 
stand habitual  exposure  to  intense  cold,  very  materially  lessened  his 
power  of  resistance.  On  the  other  hand,  the  experience  of  almost 
every  trout-fisherman  or  sportsman  has  satisfied  him  that  spirits  do 
have  power  to  prevent  ' '  catching  cold' '  under  sudden  and  unaccus- 
tomed exposure  to  wet  and  cold,  and  that  benumbed  extremities  will 
become  warm  and  have  their  proper  feelings  return  under  the  influence 
of  a  glass  of  whiskey.  There  is,  however,  nothing  strange  or  con- 
tradictory in  these  experiences,  and  they  are  both  in  strict  accord  with 
our  present  knowledge  of  the  physiological  action  of  the  drug.  As  is 
often  the  case,  the  facts  were  practically  made  out,  however,  before  sci- 
ence could  solve  the  apparent  paradox.  It  has  been  abundantly  shown 
that  alcohol  has  no  heating  power  ;  but  the  chill  of  sudden  exposure,  the 


CARDIAC   STIMULANTS.  309 

suffering  benumbed  extremities,  the  bronchitis  that  perhaps  follows,  ail 
mean  simply  this  :  that,  as  a  result  of  the  cold,  the  blood  leaves  the  sur- 
face and  the  extremities,  the  circulation  fails  in  the  outposts,  and,  as  a 
consequence,  suppressed  perspiration — i.e.,  suspended  function  of  the 
skin — and  internal  congestions  follow.  The  relief  afforded  by  the  spirits, 
as  well  as  the  prevention  of  sickness,  is  due  simply  to  the  power  of  the 
remedy  in  maintaining  the  circulation  and  keeping  the  external  surfaces 
warmed  by  the  constantly  renewed  currents  of  fresh  blood  from  the 
interior  of  the  body. 

As  an  antiseptic  alcohol  is  sufficiently  active  to  be  useful  on  occasion 
as  a  dressing  for  wounds.  Lint  soaked  and  kept  constantly  wet  with 
spirits  may  be  applied. 

ADMINISTRATION. — Almost  enough  has  been  already  said  upon  this 
point,  but  a  few  further  remarks  seem  appropriate.  When  stimulants 
are  used  to  sustain  the  sinking  powers  in  poisoning  or  in  disease,  the 
amount  given  should  be  almost  solely  regulated  by  the  effects.  Thus, 
in  snake-bite  it  may  be  necessary  to  give  a  pint  of  whiskey  in  the  course 
of  an  hour  ;  and  in  low  fevers  we  have  seen  the  greatest  benefit  result, 
and  life  apparently  saved,  by  the  exhibition  of  a  quart  of  spirits  a  day. 
In  snake-poisoning,  one,  two,  three,  or  four  ounces,  as  the  case  may 
seem  to  need,  should  be  exhibited  every  ten  minutes  until  some  effect 
is  produced  or  matters  become  hopeless.  In  low  fevers  half  an  ounce 
to  an  ounce  should  be  given  every  one,  two,  or  three  hours,  pro  re  nata, 
the  practitioner  watching  the  results. 

The  question  of  choice,  of  course,  comes  up  in  every  case  as  to 
which  of  the  spirits  shall  be  used.  We  have  never  been  able  to  perceive 
any  distinct  differences  in  their  action  (gin,  of  course,  being  excepted), 
save  only  that  sometimes  one  spirit  agrees  better  with  the  stomach  than 
another.  This  has  seemed  to  us  to  depend  simply  upon  the  personal 
likings  of  the  patient,  to  which,  therefore,  the  choice  may  well  be  left. 
In  sudden  collapse,  some  of  the  wines  with  a  very  high  bouquet  are  be- 
lieved to  be  more  stimulating,  on  account  of  the  ethers  which  they 
contain.  In  convalescence,  and  for  habitual  use  in  health,  wines  are 
preferable  to  spirits, — more  agreeable,  more  tonic,  and  less  apt  to  lead  to 
excessive  indulgence. 

When  a  mild  stimulant  is  wanted  in  the  beginning  of  fevers,  especially 
if  milk  punch  seems  too  ' '  heavy, ' '  wine  whey  may  sometimes  be  used 
with  advantage.  It  is  made  by  pouring  a  half-pint  of  sherry  or  madeira 
into  a  pint  of  boiling  milk,  stirring  thoroughly,  and,  after  coagulation  has 
occurred,  straining  off  the  whey,  which  may  or  may  not  be  sweetened,  ac- 
cording to  the  taste  of  the  patient.  Mulled  wine  is  often  very  grateful  to 
patients  as  a  change.  It  is  made  by  beating  an  egg  up  thoroughly  with 
three  fluidounces  of  sherry  and  adding  a  like  quantity  of  water,  which 
must  be  actually  boiling  when  poured  in.  Champagne  is  useful  in 
patients  with  delicate  stomachs,  especially  if  nausea  or  vomiting  actually 
exists,  and  also  may  be  employed  with  advantage  in  sudden  failure  of  the 


310  GENERAL    REMEDIES. 

vital  powers,  especially  in  elderly  persons.  It  must  always  be  very 
"  dry," — i.e.,  as  free  as  possible  from  sugar. 

Milk  punch  is  prepared  by  adding  from  a  dessertspoonful  to  a  fluid- 
ounce  of  brandy,  whiskey,  or  rum,  according  to  the  degree  of  stimula- 
tion required  and  the  taste  of  the  patient,  to  three  fluidounces  of  milk, 
with  sugar  and  nutmeg  to  taste.  The  addition  of  a  tablespoonful  of 
lime-water  is  not  recognized  by  the  palate,  and  renders  the  beverage 
more  acceptable  to  the  stomach  when  the  latter  is  weak. 

Eggnog  is  still  more  nutritious  than  milk  punch,  but  is  "  heavier," 
and  is  usually  rejected  by  the  stomach  if  given  too  freely.  It  is  made 
by  beating  up  thoroughly  the  yolk  of  an  egg  with  five  fluidounces  of 
milk  and  half  a  fluidounce  to  one  fluidounce  of  spirits  (and  half  a 
fluidounce  of  lime-water  if  required),  and  adding  a  sufficiency  of  sugar, 
with  finally  the  white  of  the  egg  previously  thoroughly  beaten  into  a  froth. 

TOXICOLOGY. — The  acute  form  of  alcoholic  poisoning  in  its  minor 
degrees  is,  unfortunately,  an  hourly  occurrence  almost  in  every  village, 
but  that  fatal  results  are  not  absolutely  so  rare  as  is  generally  believed 
is  shown  by  the  fact  mentioned  by  Taylor,  that  in  four  years  (1863-67) 
thirty-five  deaths  from  this  source  occurred  in  England  and  Wales. 
It  is  worthy  of  note  that  in  some  fatal  cases  convulsions  have  preceded 
death.58  The  absolute  diagnosis  of  acute  alcoholic  poisoning  when  the 
patient  is  simply  seen  in  the  advanced  stage  of  deep  coma  cannot  be 
made  out.  The  odor  of  liquor  upon  the  breath  or  about  the  person  is 
simply  a  proof  that  the  subject  has  been  drinking,  not  that  the  symptoms 
are  caused  by  alcohol.  The  manifestations  are  merely  those  of  profound 
compression  or  congestion  of  the  brain,  of  apoplexy,  of  opium-poisoning  ; 
and  a  man  whose  breath  and  urine  are  loaded  with  alcohol  may  have 
been  struck  down  with  apoplexy  or  poisoned  with  opium.  Whenever  in 
drunkenness  no  answer  is  obtainable  by  shaking  or  hallooing  at  the 
subject,  the  existence  of  apoplexy  should  be  strongly  suspected,  and  a 
very  careful  examination  made  to  detect  facial  or  other  palsy  ;  even  if 
this  be  not  found,  judgment  should  be  suspended.  As  in  apoplexy  the 
bodily  temperature  is  frequently  elevated,  whilst  in  acute  alcoholism  it  is 
either  normal  or  subnormal,  the  existence  of  fever  would  strongly  indicate 
cerebral  hemorrhage. 

A  congested  ecchymotic  condition  of  the  mucous  membrane  of  the 
stomach  is  the  only  lesion  at  all  characteristic  of  an  acute  alcoholic- 
poisoning. 

The  treatment  is  very  similar  to  that  of  opium-poisoning  except  that 
in  many  instances  care  should  be  taken  to  maintain  the  bodily  tempera- 
ture. The  stomach  should  be  evacuated,  the  patient  aroused  by  me- 
chanical means,  strychnine  and  digitalis  given  hypodermically,  the  hot 
bath  employed  if  necessary,  and,  finally,  if  symptoms  come  to  the  ex- 
treme, long-continued  artificial  respiration  (Sylvester  or  forced)  should  be 
practised.  For  the  purpose  of  aiding  in  the  elimination  of  alcohol  large 
quantities  of  normal  saline  solution  should  be  given  by  enemata,  or  pre- 


CARDIAC   STIMULANTS.  311 

ferably  by  hypodermoclysis.      (For  case,  see    F.  C.    Foster,   B.  M.  J., 

1903.  »•)• 

The  results  of  chronic  alcoholic-poisoning,    by  their  frequency  and 

importance,  have  come  practically  to  rank  among  diseases,  and  are  dis- 
cussed in  treatises  upon  the  practice  of  medicine,  to  which  the  reader  is 
referred. 

METHYLIC  ALCOHOL. — Pyroxylic  spirits.  Wood  alcohol.  Methyl  alcohol. 
Columbian  spirits. — This  monatomic  alcohol  is  a  mobile,  colorless  liquid,  of  a  hot, 
pungent  taste  and  aromatic  odor,  highly  inflammable,  mixing  in  all  proportions 
with  alcohol  and  ether.  It  is  usually  obtained  by  the  destructive  distillation  of 
wood,  and  on  account  of  its  cheapness  is  largely  used  in  the  arts  as  a  solvent. 

Methylic  alcohol  is  capable  of  producing  an  intoxication  similar  to  that  caused 
by  ethylic  alcohol,  but  distinct  in  the  slowness  of  the  onset  and  the  extraordinary 
duration  of  the  symptoms,  which  may  last  from  three  to  four  days  after  the  com- 
paratively moderate  dose  of  the  drug.  After  distinctly  toxic  doses  the  fall  of  the 
bodily  temperature  is  very  marked,  and  convulsive  movements  of  rhythmic  or 
choreic  character,  followed  in  a  day  or  two  by  loss  of  sensation  and  reflex  move- 
ments are  common  phenomena.  Hemorrhage  also  frequently  occurs  from  the 
abdominal  tract.  The  eyes  are  especially  affected,  nystagmus  of  a  pronounced 
type  often  being  present,  also  dilatation  of  the  pupil.  Chronic  methylic-alcohol 
poisoning  is  far  more  dangerous  than  is  ordinary  alcoholism,  and  amblyopia  due  to 
degenerative  changes  in  theganglion  cells  of  the  retina  is  a  very  common  phenomenon. 
Both  in  human  and  experimental  poisoning  excessive  fatty  degeneration  of  the  liver 
and  other  organs  is  usually  found  after  death.  Jelliffe  *  reports  multiple  neuritis 
following  the  ingestion  of  methyl  alcohol,  and  also  after  inhalation  of  the  fumes. 

Methylic  alcohol  amblyopia  may  appear  after  a  single  debauch.  It  is  accom- 
panied with  contraction  of  the  fields,  absolute,  usually  central,  scotoma,  and  rapid 
failure  of  vision  ;  and,  though  temporary  improvement  may  occur,  in  ninety  per 
cent,  of  the  cases  it  ends  in  permanent  loss  of  useful  vision.  It  is  worthy  of  note 
that  in  many  cases  methylic  alcohol  amblyopia  has  resulted  from  the  excessive  use 
of  essence  of  ginger  or  peppermint,  or  other  aromatics,  in  which  the  alcohol  has 
been  used  as  a  menstruum.  It  has  also  been  caused  by  the  absorption  of  the  alcohol 
through  the  lungs  and  skin.  It  has  been  shown  by  A.  Birch-Hirschfeld 2  that  the 
methyl-alcohol  amblyopia  is  accompanied  by  demonstrable  changes  of  the  retinal 
nerve-cells,  and  also  of  the  optic  nerve. 

The  permanency  and  severity  of  the  symptoms  caused  by  methylic  alcohol 
depend  in  part  upon  the  slowness  of  its  elimination,  and  in  part  upon  the  fact  dem- 
onstrated by  Reed  I  lunt, — that  it  is  oxidized  in  the  system  with  the  formation  of 
formic  acid,  a  highly  poisonous  substance. 

Methylic  alcohol  has  been  used  to  some  extent  in  practical  medicine,  but  ap- 
pears to  have  no  other  remedial  properties  than  those  of  ethylic  alcohol,  and  to  be 
a  much  more  dangerous  remedy.  It  has  very  properly  fallen  into  complete  desue- 
tude as  a  medicine. 

The  treatment  of  methylic-alcohol  poisoning  is  very  unsatisfactory.  The  best 
that  can  be  done  is  to  aid  in  the  elimination  of  the  alcohol  and  of  the  products  of 
its  destruction  within  the  body  by  free  sweating  and  by  the  administration  of  large 
quantities  of  slightly  alkalinized  water  with  sodium  carbonate.* 

*See  Moulton  (/.  A.  M.  A.,  Nov.  1901);  Swan  M.  Burnett  (T.  G.,  Dec.  1901);  F. 
Buller  and  Casey  A.  Wood  (/.  A.  M.  A.,  Oct.  1904)  ;  also  Von  Graefe  (Arch.  f.  Opth., 
Bd.  lii.  ;  Bd.  liv.). 


3i2  GENERAL  REMEDIES. 

DIGITALIS.     U.  S. 

The  leaves  of  the  Digitalis  purpurea,*  or  foxglove,  of  the  second  year's 
growth.  These  are  large  leaves,  of  a  dull  pale  green,  with  whitish  down 
underneath,  and  have  a  bitter,  nauseous  taste  and  a  faint  narcotic  odor. 
Digitalis  yields  both  to  water  and  to  alcohol. 

Concerning  the  active  principles  of  digitalis  there  has  been  much  con- 
fusion, partly  owing  to  the  slowness  and  irregularity  of  the  development 
of  our  chemical  knowledge,  and  partly  to  the  use  of  the  same  terms  with 
different  meanings.  The  following  epitome  will  probably  serve  the  pur- 
pose of  the  student. 

The  term  digitalin  has  been  used  for  a  number  of  different  substances. 
Originally  it  was  applied  to  two  more  or  less  purified  extracts. 

First.  Digitalinum  Gallicum,  or  French  Digitalin,  recognized  by  the 
French  and  Belgian  pharmacopoeias,  characterized  by  its  insolubility  in 
water.  It  is  said  to  be  composed  chiefly  of  digi toxin,  and  has  been  used 
in  doses  up  to  0.002  Gm.  (one-thirtieth  of  a  grain)  a  day. 

Second.  Digitalinum  Gerwanicum,  official  in  the  German  Pharma- 
copoeia, the  digitalin  of  most  American  writers,  formerly  recognized  by  the 
United  States  Pharmacopoeia.  This  is  a  purified  extract  representing 
those  activities  of  the  digitalis  leaf  which  are  soluble  in  water.  The  com- 
position of  this  substance  seems  to  us  doubtful ;  it  has  been  claimed  by 
various  observers  to  be  a  mixture  of  digitalein,  crystallized,  or  Nativelle's 
digitalin,  digitonin,  and  digitalin  of  Kiliani  ;  also,  to  contain  0.25  per 
cent,  of  digitoxin.  The  fact  that  it  is  soluble  in  water,  whilst  digitoxin  is 
insoluble  in  water,  throws  some  doubt  upon  the  truth  of  the  repeated 
assertion  that  German  digitalin  depends  chiefly  for  its  activity  upon 
digitoxin. 

The  active  principles  which  chemists  claim  to  have  separated  from 
digitalis  are  crystallized  digitalin  or  Nativelle1  s  digitalin,  which  is  probably 
a  more  or  less  impure  form  of  digitoxin  ;  digitalinum  vemm  of  Kiliani ', 
digitalein,  digitoxin,  and  digitonin. 

Digitonin  almost  certainly  belongs  to  the  Saponin  group  of  active 
principles,  and  is  therefore  physiologically  antagonistic  to  the  cardiac 
glucosides  of  digitalis.  It  exists  in  such  small  quantity  in  the  drug  as 
probably  to  have  very  little  effect  on  its  action. 

Digitalinum  crystallatum,  or  digitin,  as  it  is  sometimes  called,  is  prob- 
ably inert,  although  this  is  denied  by  some  experimenters. 

Digitalein,  asserted  by  Schmiedeberg  to  be  a  definite  chemical  sub- 
stance, is  probably  not  of  this  nature.  According  to  the  experiments  of 
Famulener  and  Lyons,  it  is  much  less  active  physiologically  than  is  ordi- 
nary German  digitalin. 

*  The  question  whether  other  species  of  Digitalis  have  the  therapeutic  properties  of 
D.  purpurea  is  of  great  interest.  H.  Goldenberg  (Inaug.  Diss.,  Dorpat,  1892)  states  as 
the  results  of  his  experiments  that  D.  nervosa,  Stend.,  D.  gigantea,  Fisch.,  D.  eriostachys, 
Linn.,  D.  fontanesii,  Stend.,  and  D.  glandulosa  all  possess  more  or  less  of  the  physio- 
logical properties  of  the  official  species,  whilst  D.  ferruginea,  Linn.,  is  ten  times  as  power- 
ful as  the  official  drug. 


CARDIAC   STIMULANTS.  313 

Digitoxin  is  probably  the  most  important  constituent  of  digitalis,  and 
occurs  in  the  market  as  a  white  crystalline,  slightly  bitter  substance, 
insoluble  in  water,  freely  soluble  in  alcohol  and  chloroform. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Locally,  digitalis  is  prob- 
ably a  feeble  irritant,  although  there  is  some  reason  for  believing  that  the 
gastric  disturbance  which  is  apt  to  follow  the  administration  of  the  drug 
in  full  doses,  and  which  sometimes  interferes  greatly  with  its  usefulness,  is 
at  least  in  part  of  centric  origin. 

Absorption  and  Elimination.  — Digitalis  yields  its  active  principles  to 
absorption  in  the  intestinal  tract  with  the  greatest  slowness  and  with  some 
irregularity,  hours  usually,  and  sometimes  days,  elapsing  before  the  full 
effect  of  the  dose  taken  by  the  mouth  is  produced.  Even  when  the  drug 
is  given  hypodermically  the  slowness  of  its  absorption  renders  it  an  unre- 
liable remedy  in  emergencies.  Concerning  the  fate  of  its  active  princi- 
ples in  the  body  we  have  no  positive  knowledge.  The  experiments  of 
G.  H.  Roger3  indicate  that  they  are  not  destroyed  in  the  liver,  and  they 
probably  escape  from  the  system  through  the  kidneys. 

General  Action.  — The  first  evidences  of  the  effect  of  moderate  doses 
of  digitalis  are  an  increase  in  the  force  and  a  slowness  in  the  rate  of  the 
pulse,  the  pulse-wave  becoming  extremely  large  and  hard.  If  the  doses 
be  increased,  dicrotism  develops,  and  increases  until  the  pulse  becomes 
rapid,  broken,  irregular,  and  feeble.  During  all  this  period  no  symptoms 
are  ordinarily  produced  ;  after  toxic  doses,  however,  there  are  gastric 
uneasiness  or  vomiting,  lassitude,  prostration,  muscular  tremors,  lowered 
reflex  activity,  and  sometimes  convulsions.  (See  also  Toxicology.} 

Nervous  System. — Upon  the  cerebrum  digitalis  has  no  influence  ;  in- 
deed, its  effects  upon  the  nervous  system  are  everywhere  so  feeble  that 
they  are  not  apparent  except  after  the  very  largest  toxic  dose. 

As  was  first  pointed  out  by  A.  Weil,4  digitalis  first  lessens  reflex 
activity  by  directly — i.  e. ,  independently  of  its  action  on  the  circulation — 
exciting  the  inhibitory  reflex  centres  of  Setschenow,  and  after  a  time  by 
directly  paralyzing  the  spinal  cord. 

Weil's  experiments  were  in  two  series.  In  the  first  series  it  was  found  that 
after  small  toxic  doses  of  the  poison  great  diminution  in  the  reflex  activity  of  the 
frog  was  apparent  in  from  ten  to  twenty  minutes,  and  continued  until  the  death  of 
the  batrachian,  but  that  this  diminution  for  from  twenty-five  minutes  to  an  hour  was 
immediately  suspended  by  section  of  the  cord  high  up,  the  reflex  activity  returning 
at  once  to  its  normal  state ;  that  after  large  doses  the  reflex  movements  were 
almost  abolished  in  five  minutes,  and  continued  so  until  death,  but  at  any  time 
during  the  first  ten  or  twenty  minutes  they  could  at  once  be  restored  by  section  of 
the  upper  cord  ;  and  that,  both  after  large  and  after  small  toxic  doses,  a  time  finally 
came  when  division  of  the  cord  had  no  power  to  restore  the  lost  reflex  functions. 
These  experiments  have  been  confirmed  by  Meihuizen.5  In  Weil's  second  series  of 
experiments  it  was  proved  that  the  action  of  digitalis  upon  the  inhibitory  reflex 
centres  and  the  cord  is  direct.  In  these  experiments  the  hearts  of  frogs  were  cut 
out,  or  their  motion  arrested  by  the  local  application  of  a  concentrated  solution  of 
potassium  nitrate,  or  rendered  slower  by  a  dilute  solution  of  the  same  salt,  and  the 
effects  of  these  various  procedures  upon  the  reflex  activity  were  studied.  It  was 


314  GENERAL   REMEDIES. 

found  that  slowing  of  the  heart's  action  did  excite  the  Setschenow's  centre,  but  not 
to  nearly  so  great  an  extent  as  did  digitalis,  and  that  minute  doses  of  digitalis  some- 
times stimulated  the  Setschenow's  ganglion  and  lowered  reflex  activity  before  the 
heart  was  sensibly  affected.  In  regard  to  the  spinal  cord  it  was  proved  that  when 
the  heart  was  killed  by  the  local  action  of  potash  the  reflex  functions  of  the  spinal 
ganglia  remained  intact  for  a  much  longer  period  than  when  digitalis  was  ad- 
ministered. 

Muscles. — That  digitalis  has  some  influence  upon  the  voluntary  mus- 
cles has  been  proved  by  the  researches  of  Vulpian,  of  Dybkowsky  and 
Pelikan,6  and  of  Gourvat,7  all  of  whom  have  found  that  the  muscles  of 
frogs  poisoned  with  digitalis  respond  more  freely  than  is  normal  to  gal- 
vanic currents.  This  action  upon  the  voluntary  muscles  is,  however,  so 
feeble  that  according'  to  Gourvat  it  is  distinctly  less  than  the  influence 
exerted  upon  the  nerves.  There  is  some  reason  for  believing  that  digi- 
talis affects  also  the  non-striated  muscle-fibres  throughout  the  body. 

Circulation. — Although  the  action  of  digitalis  upon  the  circulation  in 
reptiles  and  mammals  is  very  similar,  there  seem  to  be  certain  points  of 
difference  for  which  no  satisfactory  explanation  is  forthcoming. 

Batrachian. — In  the  frog,  during  the  first  stages  of  digitalis  action  the 
blood- pressure  is  elevated  and  in  the  last  stage  depressed.  Usually  the 
first  symptom  produced  is  a  slowing  of  the  heart's  action,*  due  to  a  pro- 
longation of  the  diastole,  which  may  be  complete,  but  sooner  or  later  is 
divided  by  an  abortive  attempt  at  ventricular  contraction.  The  systole  is 
abnormally  energetic,  so  that  the  ventricles  become  white  as  the  last  drop 
of  blood  is  squeezed  out  of  them.  As  the  action  of  the  drug  grows  more 
intense,  the  rhythm  of  the  heart  is  very  much  affected,  the  ventricle 
and  auricle  no  longer  beating  in  accord.  At  the  same  time  the  diastole 
generally  becomes  imperfect,  one  portion  of  the  ventricle  maintaining 
its  systolic  spasm,  while  the  rest  dilates.  Thus,  the  extreme  apex  may 
remain  hard  and  white  during  the  diastole,  and  even  hernial  protrusions 
of  the  ventricle  may  occur.  Finally,  the  heart  is  arrested  in  systole,  and 
as  the  muscle  so  hardens  all  power  of  responding  to  electrical  or  other 
excitants  is  lost. 

In  some  rare  instances,  instead  of  the  above  series  of  phenomena,  the 
diastolic  periods  throughout  are  prolonged  and  quiet,  and  after  several 
periods  of  relaxation,  lasting  for  ten  or  twenty  seconds,  final  diastolic 
arrest  may  occur. 

It  would  appear  definitely  settled  that  the  cardiac  phenomena  pro- 
duced by  digitalis  in  the  frog  are  due  in  part  to  a  direct  action  upon  the 
heart  itself. 

Boehm  *  and  Dybkowsky  and  Pelikan  have  found  that  the  slowing  of  the  heart's 
beat,  the  increased  energy  of  contraction,  and  the  irregularity  and  final  systolic 
arrest  are  produced  by  digitalis  after  division  of  the  vagi  and  destruction  of  the 

*  Some  observers  have  noted  a  primary  acceleration  of  the  heart's  action,  but  this  has 
occurred  so  rarely  that  it  probably  has  been  due  to  some  extraneous,  unnoticed  cause. 


CARDIAC   STIMULANTS.  315 

spinal  cord.  Again,  the  local  application  of  digitalis  at  once  influences  the  heart 
(T.  Lauder  Brunton9).  Moreover,  R.  Boehm,  using  the  method  of  Ludwig  and 
Coats,  has  determined  that  in  the  isolated  frog's  heart  digitalis  slows  the  rate  of  the 
beat  but  increases  the  expenditure  of  power  by  the  heart. 

After  a  large  dose  the  condition  of  cardiac  stimulation  is  followed  by  a 
great  lessening  in  the  output  of  power,  which  is  apparently  due  to  imper- 
fect diastole  and  consequent  non-admission  of  fluid  into  the  ventricles. 
The  heart  is  still  actually  putting  forth  more  force,  but  this  energy  is 
wasted  in  ineffectual  spasm,  and  does  not  accomplish  work.  The  experi- 
ments of  Williams 10  agree  with  those  of  Boehm  in  showing  that  the  cut- 
out frog's  heart  actually  exerts  more  than  its  normal  force  under  the 
influence  of  digitalis. 

Williams  believes  that  the  increased  work  of  the  heart  is  largely  dependent 
upon  an  altered  tone  of  the  muscle,  producing  a  more  complete  diastolic  enlarge- 
ment of  the  ventricles.* 

There  seems  to  be  no  doubt  that  the  drug  increases  the  activity  of 
the  inhibitory  ganglia  in  the  heart. 

There  is  no  stage  in  which  stimulation  of  the  vagi  does  not  cause  diastolic 
arrest.  Indeed,  Dybkowsky  and  Pelikan  have  seen  galvanization  of  nerves  produce 
such  relaxation  in  the  auricles  after  the  ventricles  had  already  become  permanently 
contracted.  Further,  Boehm  has  found  that  a  stimulation  of  the  pneumogastrics 
which  is  insufficient  to  make  itself  felt  before  poisoning  will,  after  the  exhibition  of 
digitalis,  cause  diastolic  arrest  lasting  for  many  minutes. 

The  peripheral  cardiac  inhibitory  apparatus  shares  in  the  stimulant 
action  of  digitalis  ;  and  as  Boehm  has  found  that  after  section  of  the  vagi 
diastolic  arrest  never  takes  place  in  frogs  poisoned  with  the  drug,  it  is 
probable  that  this  rare  mode  of  death  is  really  due  to  superexcitation  of 
the  cardiac  inhibitory  nerves. 

On  the  other  hand,  however,  it  does  not  appear  that  the  condition  of 
inhibitory  excitement  is  the  sole  cause  of  the  slowing  of  the  pulse,  since 
Boehm  affirms  that  not  only  are  the  partial  contractures  and  the  systolic 
arrest  of  the  heart  produced  in  the  atropinized  frog  by  digitalis,  but  also 
a  slowing  of  the  heart-beat. 

That  the  systolic  arrest  of  the  frog's  heart  by  digitalis  is  not  of  the 
nature  of  a  paralysis,  but  of  a  spasm,  is  indicated  by  the  fact  that  such 
drugs  as  muscarine,  applied  to  the  contracted  heart,  will  cause  it  to 

*  In  apparent  opposition  to  the  older  evidence  are  the  researches  of  Donaldson  and 
Stevens  (Journ.  of  Physiology,  iv. ).  For  an  elaborate  discussion  of  this  paper,  see  edito- 
rial in  Therap.  Gaz.,  February,  1885.  H.  von  Openchowski  (  Verhandl.  der  Congress/. 
Inner.  Med.,  1889,  viii.)  believes  that  digitalis  acts  differently  upon  the  right  heart  than 
upon  the  left,  and  especially  upon  the  right  and  the  left  coronary  artery,  causing  the 
latter  to  be  overfilled,  whilst  the  former  contains  no  more  blood  than  normal.  We  think 
that  his  evidence  is  not  sufficient  to  establish  a  theory  which  in  itself  seems  so  un- 
reasonable. 


316  GENERAL  REMEDIES. 

recommence  its  beat  (Schmiedeberg11).  The  experiments  of  Franjois 
Franck  "  upon  the  isolated  apex  of  the  heart  appear  to  show  that  digitalis 
acts  directly  upon  the  cardiac  muscle. 

According  to  our  present  knowledge,  in  the  frog  the  slowing  of  the 
heart  by  digitalis  is  due  partly  to  an  action  upon  the  peripheral  vagi  and 
partly  to  some  other  cause,  whilst  the  increased  energy  of  the  heart  is  the 
direct  result  of  the  digitalis  upon  the  muscle-fibre. 

Mammal. — In  the  mammal  the  action  of  digitalis  upon  the  circulation 
may  for  the  purposes  of  description  be  divided  into  two  stages.  During 
the  first  stage  there  is  marked  slowing  of  the  heart's  beat,  with  large,  full, 
hard  pulse-waves  and  pronounced  rise  in  the  arterial  pressure.  During 
the  second  stage  there  is  rapidity  and  usually  irregularity  of  the  heart's 
beat.  In  the  latter  part  of  the  first  stage  there  is  marked  dicrotism  of  the 
pulse,  which  increases  during  the  early  part  of  the  second  stage,  so  as  to 
convey  the  impression  that  the  increase  of  the  pulse-rate  is  due  to  the 
division  of  the  cardiac  beats. 

In  most  of  the  experiments  of  Arnold  and  Wood  upon  dogs  the 
change  from  a  slow  to  a  rapid  pulse  has  been  abrupt  and  usually  accom- 
panied by  an  enormous  rise  of  the  already  elevated  blood-pressure.  At 
the  end  the  fall  of  pressure  is  very  sudden  and  rapid,  so  that  it  has  imme- 
diately preceded  death. 

In  explaining  these  phenomena  it  will  not  suffice  to  resort  to  the  results 
obtained  in  experiments  upon  the  isolated  frog's  heart.  It  seems  to  be 
clearly  established  that  in  poisoning  of  the  mammal  by  digitalis  the  heart 
is  arrested  not  in  systole  but  in  diastole,  since  the  fact  has  been  confirmed 
by  Donaldson  and  Stevens,13  by  Cushny,14  and  recently  in  an  elaborate 
series  of  experiments  made  in  the  University  of  Pennsylvania  Laboratory 
by  John  P.  Arnold  and  Horatio  C.  Wood,  Jr. ,  the  latter  investigators 
being  well  informed  of,  and  meeting  Franck' s  denial  of  the  diastolic 
arrest.* 

Notwithstanding  these  differences,  it  would  appear  established  by  all 
the  evidence  that  the  action  of  digitalis  upon  the  mammalian  heart  is  in 
accord  with  its  influence  upon  the  batrachian  heart  in  regard  to  the  one 
great  physiological  fact  of  practical  importance, — namely,  that  the  mod- 
erate dose  of  the  drug  increases  the  force  put  out  by  the  heart ;  our  own 
experiments  would  indicate  that  this  excessive  cardiac  energy  in  the 
mammal  as  well  as  in  the  batrachian  may  persist  to  the  last. 

The  question  how  digitalis  primarily  slows  and  secondarily  increases 
the  pulse-rate  in  the  mammal  has  been  variously  answered.  In  his  origi- 
nal memoir,  upon  which  has  been  founded  our  modern  knowledge  of  the 

*  That  there  are  apparent  important  differences  in  the  relations  of  certain  drugs  or 
drug-forces  to  the  mammalian  and  batrachian  heart  seems  established,  but  the  probabili- 
ties are  that  these  differences  are  due  to  extraneous  causes  and  are  not  essential.  Thus, 
according  to  the  experiments  of  Masi,  when  the  frog's  heart  is  warmed  to  32°  C.,  digi- 
talis arrests  it  in  diastole,  and  when  the  heart  of  the  mouse  is  cooled,  digitalis  stops  it  in 
systole  instead  of  diastole  ;  whilst  Donaldson  and  Stevens  have  shown  that  the  condition 
of  the  venous  circulation  very  materially  affects  the  heart-action  of  frogs. 


CARDIAC   STIMULANTS.  317 

physiological  action  of  digitalis,  Traube  stated  that,  after  section  of  the 
vagi,  digitalis  is  in  warm-blooded  animals,  with  rare  exceptions,  incapable 
of  reducing  the  pulse-rate,  and,  contrariwise,  that  when  the  pulse-fre- 
quency has  been  reduced  by  the  drug,  section  of  the  nerves  causes  an 
immediate  and  very  marked  rise  in  the  rate  of  pulsation.  Klug  also 
affirms  that  section  of  the  vagi  completely  does  away  with  the  slowing 
action  of  digitalis,  and  concludes  that  the  lessened  pulse-rate  is  entirely 
due  to  stimulation  of  the  pneumogastric  centres.  The  bulk  of  investiga- 
tors, however,  "such  as  Marme,  Ackermann,  Bulgari,  Schnabl,  Popper, 
and  Kaufmann"  (quoted  from  Cushny),  have  found  that  section  of  the 
pneumogastric  does  not  completely  prevent  the  slowing  of  the  cardiac 
rate.  This  would  seem  to  indicate  that  in  the  mammal  digitalis  stimu- 
lates centrically  the  inhibitory  nerve  of  the  heart,  whilst  at  the  same  time 
also  in  some  other  way  it  decreases  the  rate  of  the  cardiac  pulsations. 
When  to  this  conclusion  is  added  the  fact  seemingly  established  by  the 
separate  researches  of  Ackermann,  of  Arthur  R.  Cushny,  and  of  Arnold 
and  Wood,  Jr.,  that  the  administration  of  atropine  entirely  does  away 
with  the  slowing  of  the  pulse  in  the  mammal,  it  would  appear  that  this 
slowing  of  the  pulse  is  due  to  a  simultaneous  stimulation  of  the  pneumo- 
gastric centres  and  of  the  peripheral  inhibitory  apparatus  in  the  heart. 

It  is  probable  that  the  comparative  effects  of  digitalis  upon  the  pneu- 
mogastric centre  and  periphery  differ  in  different  individuals,  the  centric 
influence  usually  being  the  most  powerful,  but  in  some  cases  the  nerve- 
ending  being  even  more  susceptible  to  the  action  of  the  drug  than  is  the 
centre  ;  in  this  way  the  very  pronounced  reduction  in  the  pulse-rate 
occasionally  produced  by  digitalis  in  the  mammal  after  section  of  the 
pneumogastric  may  be  explained  as  due  to  an  exceptional  sensitiveness 
of  the  peripheral  ganglia  of  the  individual  animals  under  experimenta- 
tion. 

In  the  advanced  stages  of  digitalis-poisoning  in  the  mammal  there 
appears  to  be  paralysis  of  the  pneumogastric  peripheral  ending,  or  else 
such  exceptional  irritability  of  the  muscle-fibres  that  the  pneumogastric 
nerve  has  lost  its  control,  since  at  this  period  galvanization  of  the  pneu- 
mogastric does  not  perceptibly  affect  the  cardiac  action  (Cushny,  Arnold 
and  Wood,  Jr.,  and  others). 

Digitalis  has  a  very  marked  action  upon  other  portions  of  the  mam- 
malian heart  than  those  connected  with  inhibition.  In  the  first  period  of 
its  action  the  diastole  is  more  complete  and  the  systoles  more  powerful 
and  also  thorough,  so  that  the  ventricle  is  more  completely  emptied 
of  its  blood  than  in  the  ordinary  normal  contraction.  In  advanced 
stages  of  the  poisoning  the  movements  of  the  heart  are  arhythmical, 
but  the  ventricular  contractions  become  very  rapid,  and  apparently 
do  not  lose  their  force  ;  at  least  in  our  own  experiments  in  the  Uni- 
versity laboratories,  with  the  exposed  mammalian  heart  under  observa- 
tion, the  change  from  the  first  period  of  slow  pulse  showed  itself  in  a 
rapid  alteration  of  the  systolic  contractions,  which  become  progressively 


3i8  GENERAL    REMEDIES. 

faster  and  faster,  there  being  at  the  same  time  a  very  marked  increase  in 
the -arterial  pressure.  At  the  end  there  was  a  sudden  and  complete  fall 
of  the  arterial  pressure,  this  being  simultaneous  to  and  probably  depend- 
ent upon  the  ventricles  passing  into  a  condition  of  violent  imperfect  fibril- 
lary  contractions  similar  to  that  which  has  been  called  flimmerbewegung 
by  Kronecker. 

The  rhythmic  action  of  the  ventricles  and  auricles  is  not  affected  by 
the  therapeutic  dose  of  digitalis,  but  after  the  toxic  dose,  at  the  period 
when  the  slow  beat  is  changing  into  the  rapid,  the  normal  relations  be- 
tween the  contractions  of  the  various  portions  of  the  heart  are  often  lost. 
In  the  last  period  of  the  poisoning  the  auriculo-ventricular  arhythmia 
grows  more  pronounced,  and  finally  the  cardiac  contractions  become  en- 
tirely irregular,  until  at  last  there  is  that  condition  which  is  sometimes 
spoken  of  as  delirium  cordis. 

If  the  belief  of  Cushny,  that  the  differences  in  the  final  result  in  the  digitalized 
batrachian  and  mammalian  hearts  are  because  the  mammalian  heart  is  not  capable 
of  continuous  systole,  be  correct,  the  only  marked  difference  in  the  action  of  the 
drug  upon  the  two  hearts  is  in  the  effect  upon  the  inhibitory  apparatus. 

It  does  not  seem  to  us,  however,  that  the  whole  matter  has  as  yet  been  worked 
out.  Neither  the  theories  advanced  by  Cushny,  that  the  arhythmia  and  peculiar 
ventricular  movements  of  the  third  stage  of  digitalis-poisoning  are  the  results  of 
excessive  irritability  of  the  cardiac  muscle,  and  that  these  and  otUer  cardiac 
phenomena  in  the  last  stage  of  digitalis  action  are  produced  by  poisons  formed  in 
the  heart  itself  by  its  own  action,  nor  the  theory  that  the  advanced  phenomena  of 
digitalis  cardiac  action  are  largely  due  to  excessive  stimulation  of  the  accelerators, 
appear  to  us  to  be  established.  In  our  experiments  upon  the  exposed  mammalian 
heart  we  have  seen  in  the  final  acts  of  the  digitalis  drama  happenings  so  curious 
and  unexpected  that  at  present  no  proposed  theory  as  to  the  action  of  the  drug  is 
sufficient. 

The  question  as  to  the  comparative  action  of  digitalis  upon  the  ven- 
tricles and  the  auricles  is  one  of  distinct  practical  bearing,  but  cannot  at 
this  time  be  fully  answered,  although  it  is  probable  that  the  drug  affects 
the  ventricles  more  than  it  does  the  auricles.  Kaufmann  states  that  he 
has  experimentally  proved  that  the  diastolic  as  well  as  the  systolic  intra- 
ventricular  pressure  is  increased  by  digitalis,  but  that  the  diastolic  intra- 
auricular  pressure  is  slightly  diminished.  This  would  indicate  stimulation 
of  the  auricles  as  well  as  of  the  ventricles.  The  pressure  within  the 
auricles  would  naturally  not  be  increased,  because  digitalis  does  not 
increase  the  flow  of  blood  from  the  lungs  into  the  auricle  ;  on  the  other 
hand,  the  intra-ventricular  pressure  during  diastole  would  naturally  be 
increased  by  any  increase  in  the  power  of  the  auricle. 

Although  digitalis  does  increase  the  muscular  energy  of  the  heart,  it 
seems  scarcely  possible  that  the  enormous  rise  of  pressure  produced  by 
it  can  be  owing  to  this  alone.  This  a  priori  reasoning  has  received  ex- 
perimental confirmation  from  Malan  (quoted  by  Fothergill),  Fothergill, 15 
Gourvat,  and  Ackermann,16  who  have  found  by  microscopic  studies  that 
the  arterioles  of  the  frog's  web,  or  of  the  mesentery  of  the  rabbit,  undergo 


CARDIAC   STIMULANTS.  319 

very  marked  contraction,  even  to  the  partial  obliteration  of  their  lumen, 
after  the  exhibition  of  digitalis.  Without  attaching  too  much  importance 
to  this  evidence,  the  finding  of  Traube,  of  Boehm,  and  of  others,  that  after 
section  of  the  cord  high  up  the  arterial  pressure  is  either  elevated  not  at 
all  or  not  nearly  so  much  by  digitalis  as  in  the  normal  animal,*  is  a  strong 
indication  that  the  drug  increases  the  arterial  pressure  largely  by  increasing 
the  peripheral  resistance  without  centric  vaso-motor  stimulation.  There 
is,  moreover,  much  still  weightier  evidence  of  the  truth  of  this  conclusion. 

J.  F.  Williams  has  also  found,  after  reduction  of  blood-pressure  to  zero  by 
chloral,  that  digitalis^will  cause  rise  of  pressure.  This  does  not,  however,  throw 
much  light  upon  the  vaso-motor  action  of  the  drug,  because  by  enormous  doses  of 
chloral  the  heart  is  almost  as  much  affected  as  is  the  vaso-motor  system.  Brunton 
and  Meyer  injected  digitalin  into  the  ear  of  a  rabbit  whose  cervical  sympathetic  and 
pneumogastrics  had  been  destroyed,  but  were  unable  to  obtain  any  satisfactory 
result ;  there  was  certainly  no  constant  perceptible  contraction,  although  sometimes 
the  vessels  were  seen  to  empty  themselves  more  rapidly  than  before  the  injection. 
More  important  is  the  fact  demonstrated  by  Brunton  and  Tunnicliffe,17  that  during 
an  inhibitory  cardiac  arrest  the  blood-pressure  sinks  much  less  when  digitalis  is 
given  than  without  it.  Decisive  are  the  independent,  though  consentaneous, 
researches  of  Ringer  and  Sainsbury 18  and  of  Donaldson  and  Stevens,  who,  using 
the  method  of  Gaskell  more  or  less  modified,  have  apparently  proved  that  digitalis 
acts  upon  the  walls  of  the  arterioles.  They  destroyed  the  nerve-centres  of  a  terrapin, 
excised  the  heart,  and  connected  bottles  in  such  a  way  with  the  blood-vessels  that 
liquids  would  run  through  the  arteries  and  come  out  through  the  veins.  Under 
such  circumstances  they  noted  a  marked  reduction  of  the  rate  of  flow  when  soluble 
digitalin  was  placed  in  the  artificial  serum.  That  in  the  normal  mammal  under  the 
influence  of  digitalis  there  is  pronounced  contraction  of  the  blood-vessels  seems 
also  to  be  proven  by  the  experiments  of  John  C.  Hemmeter,  made  with  Ludwig's 
stromuhr,  in  which  it  was  found  that  the  velocity  of  the  blood-current  was  markedly 
decreased  by  digitalis,  though  the  pressure  was  increased.  R.  A.  Robert 19  f  in  a 
series  of  experiments  similar  in  principle  to  those  of  Ringer  and  Sainsbury,  but 
made  upon  the  excised  kidney,  found  that  digitalis  retards  greatly  the  flow  of 
liquid  through  the  organ,  and  therefore  acts  directly  upon  the  coats  of  the  smaller 
vessels;  also  that  digitalis  and  the  nitrites  are  mutually  antagonistic. 

*  These  experiments  have  been  contradicted  by  Ackermann,  who  states  that  he  has 
many  times  cut  the  spinal  cord  and  without  exception  found  a  very  marked  rise  of  arterial 
pressure  follow  the  injection  of  digitalis.  Unfortunately,  none  of  these  experiments  have, 
that  we  are  aware  of,  been  published  in  detail,  and  it  is  therefore  impossible  to  analyze  or 
to  reconcile  them;  but  Gorz  (Schmidt's  Jahrbucher,  clviii.)  expresses  the  opinion  that 
Ackermann  did  not  fully  divide  the  cord  in  his  experiments.  Gorz  himself  found  that 
a  rise  is  produced  by  digitalin  after  division  of  the  cord,  but  of  so  small  an  amount  as 
readily  to  be  accounted  for  by  the  increased  power  of  the  heart.  A  similar  rise  has 
been  observed  by  Kaufmann,  who  does  not,  however,  give  the  extent  of  it.  It  is  ex- 
ceedingly probable  that  Gorz's  explanation  is  correct ;  moreover,  it  is  possible  that  the 
cord  in  these  cases  was  not  entirely  cut.  We  have  found  by  actual  experiment  that  a  spinal 
cord  may  be  so  divided  that  the  animal  has  neither  sensation  nor  power  of  voluntary  motion 
below  the  point  of  section,  although  sufficient  nerve-fibres  retain  their  integrity  to  trans- 
mit vaso-motor  impulses,  so  that  galvanization  of  a  sensitive  nerve  below  the  point  of  sec- 
tion produces  immediate  rise  of  the  arterial  pressure  without  eliciting  any  pain-cries  from 
the  animal. 

t  Kobert  tested  two  specimens  of  digitoxin  and  digitalein  which  had  been  supplied 
by  Schmiedeberg,  their  discoverer,  and  found  that  instead  of  contracting  the  vessels  of 
the  kidney  they  actively  dilated  them  and  increased  the  flow  of  liquid. 


320  GENERAL  REMEDIES. 

It  may  be  considered  as  definitely  proven  that  digitalis  has  a  direct 
action  upon  the  walls  of  the  aiterioles,  but  it  is  highly  probable  that  it  also 
acts  upon  the  vaso-motor  centre  in  the  medulla.  In  a  series  of  plethys- 
mographic  experiments  in  which  digitalin  and  digitoxin  were  employed, 
Gottlieb  and  Magnus  w  found  that  the  local  action  of  digitalis  upon  the 
blood-vessels  is  especially  manifested  in  the  region  of  the  splanchnic  dis- 
tribution, although  contraction  even  of  the  volume  of  the  brain  of  the  dog 
was  demonstrated  as  produced  by  digitoxin.  As  it  is  probable  that  the 
splanchnic  nerve  almost  always  dominates  the  general  blood-pressure, 
a  special  susceptibility  to  the  action  of  digitalis  is  not  surprising. 

It  has  been  shown  that  the  dicrotism  in  the  frog's  pulse  is  due  to  an  attempted 
diastole  before  the  systolic  impulse  has  yielded  ;  and  Kaufmann  has  determined 
that  in  the  mammal  a  similar  partial  relaxation,  arrested  by  a  renewed  very  brief 
systole,  occurs  and  gives  origin  to  the  double  pulse.  Kaufmann  has  also  noticed 
that  a  tendency  to  cardiac  tetanus  is  manifested  in  the  horse,  as  in  the  frog,  under 
the  influence  of  digitalis,  but  that  in  the  former  animal  a  permanent,  complete  car- 
diac spasm  never  occurs. 

The  following  proposition  expresses  our  present  knowledge,  and 
probably  is  very  close  to  the  truth  in  regard  to  the  action  of  digitalis  upon 
the  lower  mammals. 

Digitalis  in  moderate  doses  stimulates  the  musctdar -motor  portion  of 
the  heart  (probably  its  contained  ganglia),  increases  the  activity  of  the  in- 
hibitory apparatus,  and  causes  contraction  of  the  arterioles,  probably  by  an 
action  on  the  vaso-motor  centres  in  the  cord,  and  also  upon  the  walls  of 
the  arterioles.  As  a  consequence  of  the  first  action,  the  cardiac  beats 
become  much  stronger  ;  as  the  result  of  the  last,  there  is  a  narrowing  of 
the  blood-paths,  and  an  increased  resistance  to  the  passage  of  the  vital 
fluid,  which,  acting  on  the  already  excited  inhibitory  system,  aids  in  the 
slowing  of  the  pulse.* 

Man. — According  to  our  experience,  decided  therapeutic  doses  of 
digitalis,  in  man,  produce  great  reduction  of  the  pulse-rate  and  some- 
times dicrotism  of  the  pulse,  and  increase  the  size  and  force  of  the  wave, 
at  the  same  time  augmenting  the  arterial  tension.  Poisonous  doses  in- 
duce, after  a  time,  increase  of  the  pulse-rate,  with  smallness  of  the  wave. 

Sphygmographic  studies  of  the  effect  of  digitalis  upon  persons  suffer- 
ing from  various  acute  and  chronic  diseases  have  been  made  by  Le- 
groux,  Bordier,21  Constantine  Paul,2*  and  Paul  Lorrain.23  The  problems 

*  Bayet  (Acad.  Royale  de  M&d.  de  Belgique,  iv.  serie,  1892)  is  stated  to  have  found  in 
the  dog  that  the  pressure  in  the  pulmonary  artery  is  depressed  rather  than  increased 
under  the  action  of  digitalis  and  strophanthus  at  a  time  when  the  aortic  pressure  is  enor- 
mously augmented.  The  importance  of  this  is  easily  seen ;  it  implies  an  extraordinary 
physiological  disassociation  between  the  right  and  left  heart,  and  has  also  very  close  rela- 
tions with  the  therapeutic  use  of  the  agents  in  pneumonia  and  other  conditions.  We  have 
not  seen  any  detailed  report  of  the  experiments  of  Bayet,  nor  have  we  seen  the  memoirs  of 
Bradford  and  of  Bockenham,  who  are  quoted,  without  reference,  as  having  obtained  a 
different  result  in  1890. 


CARDIAC   STIMULANTS.  321 

offered  by  these  gentlemen  are  so  complex  as  to  render  a  detailed  study 
almost  impossible  ;  but,  as  a  whole,  their  tracings  seem  to  confirm  our 
personal  experience.  Paul  Lorrain  calls  attention  to  the  fact  that  when 
the  drug  has  reduced  the  pulse-rate  very  greatly  a  second  abortive  systole 
can,  on  auscultation,  sometimes  be  heard  occurring  during  the  long  dia- 
stole, and  some  of  his  sphygmographic  tracings  are  markedly  dicrotic. 
It  is  evident  that  in  man  the  second  systolic  movement  occurs  precisely 
as  in  animals  ;  and  it  seems  very  certain  that  the  proposition  framed  for 
the  lower  mammals  applies  also  to  man. 

When  the  pulse  has  been  reduced  by  digitalis  to  40  or  50  a  min- 
ute, the  change  from  the  recumbent  to  the  erect  position  will  not  infre- 
quently suffice  to  alter  at  once  its  character,  so  that  it  will  become  small, 
and  rapid,  even  150  per  minute.  The  explanation  of  this  seems  to  be  that 
the  heart  of  such  a  patient  is  just  in  the  position  in  which  the  diastolic 
impulse  is  being  overcome  by  the  excessive  systolic  stimulation  of  the 
drug.  While  the  patient  is  recumbent,  the  line  is  not  passed  over,  but 
the  additional  stimulation  of  the  erect  position  carries  the  heart  beyond 
the  limit  of  regular  diastole,  and  the  over-effects  of  the  drug  are  at.  once 
manifested. 

Urinary  Secretion. — The  influence  of  digitalis  upon  the  urinary  secre- 
tion in  health  has  been  studied  by  numerous  observers,  with  such  diverse 
results  as  to  prove  that  the  action  of  the  drug  on  the  kidneys  is  so  incon- 
sistent and  varying  as  to  render  it  probable  that  it  is  in  great  measure 
indirect  rather  than  direct.  Thus  Jorg,  Hammond,24  and  Brunton  have 
found  the  secretion  more  or  less  decidedly  increased,  and  Homolle,25 
Winogradoff,26  Stadion,  and,  according  to  Brunton,  also  Krahmer, 
Kluyskens,  Vassal,  and  Shohl,  have  found  it  either  uninfluenced  or 
diminished.  Kaufmann  has  found  it  uniformly  diminished  in  the  dog. 

Investigations  made  upon  the  action  of  digitalis  upon  the  elimination 
of  organic  matters  through  the  kidneys  have  yielded  such  contradictory 
results  that  at  present  the  conclusion  seems  justified  that  the  drug  has 
no  consistent  dominant  influence  upon  the  output  either  of  nitrogenous  or 
inorganic  solids  through  the  urine. 

The  urea  in  the  apparently  very  careful  experiments  of  Winogradoff,  of  Stadion,*7 
and  of  Hammond  was  diminished,  while  in  the  almost  equally  elaborate  experi- 
ments of  Brunton  it  was  increased.  All  four  observers  noted  lessening  of  the  chlo- 
rides. Me"gerand,  using  the  crystallized  digitalin  of  Nativelle,  found  his  urine 
increased  twenty-five  per  cent,  but  his  urea  diminished  twenty  per  cent.  Auguste 
Meusnier 28  has  sought  without  success  for  sugar  in  the  urine  both  of  patients  taking 
large  doses  of  digitalis  and  of  rabbits  poisoned  with  the  drug.  Kaufmann  w  states 
that  digitalis  leaves,  or  preparations  which  produce  local  irritation,  cause  in  the 
dog  an  increase  in  the  elimination  of  urea,  but  that  when  digitalin  was  given  in 
solution  the  excretion  of  urea  was  diminished.  G.  P.  Sereschnikow,  as  the  result 
of  experiments  upon  man,  finds  that  digitalis  has  no  pronounced  constant  effect 
upon  nitrogenous  elimination.  He  is  confirmed  by  Alexeevsky,30  whilst  I.  Belji- 
kow Sl  asserts  that  the  drug  increases  the  elimination  of  the  chlorides,  sulphates, 
and  phosphates. 


322  GENERAL  REMEDIES. 

Temperature. —  Toxic  doses  of  digitalis  lower  the  temperature  a  num- 
ber of  degrees  in  healthy  men  and  animals.  It  would  seem,  however, 
that  the  fall  of  temperature  is  generally,  if  not  always,  preceded  by  a 
rise,  as  has  been  noted  by  Bouley  and  Reynal,  by  Dum6ril,  Demarquay, 
and  Lecointe  (quoted  by  Brunton),  by  Hirtz,  by  Legros,"  and  by  Gour- 
vat.  Kaufmann  believes  that  such  rise  is  due  to  the  local  irritation 
caused  by  the  drug,  and  asserts  that  if  no  irritation  be  produced  there  is 
always  in  the  animal  a  fall  of  rectal  temperature  (0.4-0.5°  C. )  after  even 
a  feeble  dose  of  digitalin. 

The  effect  of  therapeutic  doses  in  the  normal  condition  has  not  been 
closely  studied,  that  we  are  aware  of.  But  in  a  number  of  cases,  chiefly 
of  pneumonia,  Z.  E.  Coblentz,"  found  that  about  twelve  hours  after  the 
fall  of  the  pulse  there  was  also  a  fall  of  temperature.  The  tendency  of 
our  present  knowledge  is  to  connect  the  changes  in  temperature  induced 
by  digitalis  with  the  changes  of  the  circulation  ;  and  it  seems  very  pos- 
sible that  therapeutic  doses  in  health  may  be  found  to  increase  bodily 
heat,  although  in  fever  they  may  diminish  it. 

SUMMARY. — It  -would  appear  to  follow,  from  experiments  upon 
frogs,  that  the  toxic  dose  of  digitalis  primarily  inhibits  reflex  action  by 
stimulation  of  Setschenow's  centre,  and  subsequently  directly  paralyzes 
the  motor  tract  of  the  spinal  cord.  This  influence  is  not,  however,  very 
apparent,  even  in  the  lower  mammals,  and  in  the  human  individual  the 
symptoms  of  digitalis-poisoning  are  chiefly  manifested  in  irritation  of 
the  stomach  and  disturbance  of  the  circulation,  death  finally  occurring 
in  collapse,  sometimes  preceded  by  delirium,  stupor,  or  convulsions, 
though  consciousness  is  long  preserved.  The  therapeutic  dose  of  digi- 
talis acts  almost  solely  upon  the  circulation,  slowing  the  rate  and  in- 
creasing the  force  of  the  heart's  beat  by  a  direct  stimulating  action  on 
the  pneumogastric  nerves  and  upon  the  heart  itself.  By  this  cardiac 
influence,  and  also  by  contracting  the  blood-vessels  through  a  direct 
action  upon  their  walls,  and  also  probably  upon  the  vaso-motor  cen- 
tres, the  therapeutic  dose  of  digitalis  enormously  increases  arterial 
pressure.  Probably  by  its  direct  influence  upon  the  heart-muscle,  and 
also  by  stimulating  the  pneumogastric  or  trophic  cardiac  nerve,  and  by 
increasing  the  blood-supply  of  the  heart,  in  certain  diseased  conditions 
digitalis  acts  not  only  as  a  cardiac  stimulant,  but  also  as  a  cardiac  tonic. 
In  the  frog  the  heart  stops  in  systolic  spasm ;  the  mammalian  heart,  after 
going  into  a  condition  of  fibrillary  contractions,  ceases  all  movement 
in  diastole.  The  active  principles  of  digitalis  are  absorbed  and  proba- 
bly eliminated  through  the  kidneys,  though  in  health  the  diuretic  action 
of  the  drug  is  extremely  uncertain.  Upon  the  alimentary  canal  digitalis 
acts  as  an  irritant,  affecting  the  stomach  more  than  the  intestines,  and 
often,  when  in  full  dose,  producing  gastric  pain  and  vomiting. 

THERAPEUTICS. — The  chief  clinical  use  of  digitalis  is  in  diseases  of 
the  heart  ;  and  from  what  has  been  said  of  its  physiological  action  it  logi- 
cally follows  that  it  should  be  useful  in  loss  of  cardiac  power. 

When  the  muscle  of  the  heart  is  for  any  reason  unequal  to  the  task 
set  it,  the  systoles  become  rapid  and  imperfect,  and  by  this  irregular 
action,  the  ventricles  neither  completely  filling  nor  completely  emptying 


CARDIAC   STIMULANTS.  323 

themselves,  increase  the  embarrassment.  Under  these  circumstances, 
digitalis,  by  lengthening  the  diastolic  pauses  and  increasing  the  force  of 
the  systolic  contractions,  causes  the  ventricles  to  fill  themselves  com- 
pletely in  the  one  and  to  empty  themselves  completely  in  the  other  act. 
By  subduing  irregular  action  through  the  inhibitory  nerves,  and  by  ener- 
gizing the  muscular  power  of  the  heart-walls,  the  remedy  is  of  incalcu- 
lable service,  and,  increasing  arterial  tension  all  over  the  body,  causes  the 
disappearance  or  lessening  of  symptoms  due  to  low  pressure  in  the  arte- 
ries. 

It  is  a  logical  necessity,  if  our  reasoning  as  to  the  physiological  action 
of  digitalis  has  led  to  a  correct  result,  that  the  drug  should  be  of  the 
greatest  service  when  the  lesion  is  simply  loss  of  cardiac  power  ;  and 
clinical  experience  tallies  with  this  a  priori  argument.  In  simple  dilata- 
tion, or  in  simple  failure  of  the  cardiac  muscle  without  degenerative 
changes  or  valvular  lesion,  the  results  of  the  use  of  digitalis  are  most 
favorable. 

On  the  other  hand,  in  simple  hypertrophy  digitalis  does  harm,  and 
should  never  be  used.  It  must  be  borne  in  mind  that  although  this 
agrees  with  what  the  experimentalist  has  proved  to  be  the  action  of  digi- 
talis, yet  it  was  discovered  independently  as  a  clinical  fact  by  practi- 
tioners. Thus,  Niemeyer,  who  ridiculed  experimental  therapeutics  be- 
cause he  would  not  take  the  trouble  to  study  them  deeply  and  practically 
and  was  therefore  incapable  of  understanding  them, — Niemeyer  says, 
"  Digitalis  in  pure  uncomplicated  hypertrophy  is  unsuitable." 

Valvular  lesion  of  the  heart,  as  is  well  known,  gives  rise  under  un- 
favorable circumstances  to  dilatation,  but  in  favorable  cases  to  hyper- 
trophy, or  rather  in  the  great  majority  of  cases  to  hypertrophy  with 
dilatation.  Following  out  the  principles  already  inculcated,  it  might 
seem  at  first  that  the  use  of  digitalis  in  hypertrophied  hearts  with  val- 
vular lesion  ought  to  be  reprobated.  But  it  is  known  clinically  that  digi- 
talis often  does  good  in  valvular  lesion  with  enlargement  of  the  heart. 
The  results  of  logical  deductions  from  our  physiological  conclusions  as 
premises  are,  however,  not  really  at  variance  with  this.  It  must  be 
borne  in  mind  that  structural  hypertrophy  and  functional  hypertrophy 
are  different  things  :  by  this  is  meant  that  although  a  heart  be  enlarged 
and  absolutely  stronger  than  normal,  yet  it  may  be,  relatively  to  the 
work  required  of  it,  weak.  Thus,  if  i  represents  the  normal  work  of 
the  heart  and  i  its  normal  power,  if  the  former  be  increased  to  4  and  the 
latter  to  3  the  heart  is  really  in  the  position  of  a  weak  organ,  although 
possessed  of  three  times  its  original  strength.  Hence  it  is  that  digitalis 
is  often  useful  in  valvular  disease  with  hypertrophy.  In  the  vast  majority 
of  cases  the  heart  with  diseased  valves  is  in  the  position  just  spoken  of ;  but 
sometimes  the  work  advances  only  to  2  and  the  strength  to  3  ;  then  the 
hypertrophy  becomes  excessive,  and  digitalis  will  increase  the  difficulty. 

In  mitral  insufficiency  and  in  mitral  stenosis  digitalis  is  often  of  great 
service.  It  is  evident  that  in  both  instances  the  valvular  lesion  leads  as 


324  GENERAL    REMEDIES. 

its  first  result  to  pulmonic  hyperaemia.  How  does  the  digitalis  lessen 
this?  In  the  case  of  stenosis,  the  diastole  being  lengthened  by  the 
remedy,  the  auricle  is  afforded  more  time  to  empty  itself  into  the  ven- 
tricle through  the  narrowed  orifice,  and  at  the  same  time  is  strengthened 
in  its  contracting  power  ;  evidently,  then,  the  left  ventricle  when  its 
systole  occurs  will  have  much  more  to  contract  on  than  before  the  digi- 
talis was  administered,  and  the  amount  of  blood  in  the  systemic  circula- 
tion will  be  increased, — i.e.,  the  amount  in  the  pulmonic  circulation  will 
be  diminished  ;  further,  the  right  ventricle  will  have  greater  power  af- 
forded it  to  force  the  blood  through  the  lungs. 

In  mitral  insufficiency  the  mechanism  is  different,  but  the  result  is  the 
same.  The  increased  power  of  the  systole  will  throw  proportionately 
more  blood  through  the  aortic  orifice  than  through  the  partially  open 
valve.  The  opening  at  the  insufficient  mitral  valve  is  much  smaller  and 
more  obstructed  than  the  aortic  orifice.  As  the  force  or  rapidity  of  the 
current  increases  under  the  action  of  digitalis,  the  friction  becomes  greater 
at  both  orifices,  but  the  ratio  of  increase  is  evidently  far  higher  in  the 
small  choked  mitral  leak  than  in  the  wide  aortic  opening.  Hence  the 
large  orifice  constantly  gains  upon  the  smaller  as  the  cardiac  force  is 
increased,  and,  more  blood  passing  into  the  systemic  circulation,  the 
pulmonic  vessels  are  relieved.  Again,  the  right  ventricle  shares  the 
stimulant  action  of  the  drug,  and  acts  more  strongly  upon  the  pulmonic 
circulation,  resisting  the  direct  backward  flow  from  the  auricle.  There 
are  cases  of  mitral  cardiac  disease  in  which  digitalis  seems  to  be  indicated, 
but  when  given  acts  unhappily.  In  some  of  these  cases  the  augmented 
distress  is  probably  caused  by  a  strain  upon  the  auricles.  If  the  ventricle 
be  already  too  strong  for  the  auricle,  and  if  by  virtue  of  a  very  patulous 
mitral  valve  the  backing  of  the  blood  upon  the  auricle  is  very  easy,  it  is 
readily  understood  how  increasing  the  power  of  the  ventricle  may  aug- 
ment the  auricular  strain.  Especially  is  this  consideration  important  in 
the  light  of  Kaufmann's  researches,  which  seem  to  show  that  the  ventricle 
is  more  affected  by  digitalis  than  is  the  auricle,  and  hence  that  a  stimu- 
lated ventricle  may  have  to  be  met  by  a  non-stimulated  auricle. 

In  aortic  constriction  digitalis  is  useful  when  the  heart-power  begins 
to  fail.  In  these  cases  compensatory  hypertrophy,  with  slowness  of 
action,  is  very  apt  to  occur,  or  even  to  become  excessive  ;  much  more 
frequently  does  this  happen  than  in  mitral  disease.  Again,  in  aortic 
insufficiency  the  prolonged  diastole  of  digitalis  action  favors  the  return 
of  blood  to  the  heart,  and  is  not  advantageous.  It  is  evident  that  digi- 
talis is  not  so  generally  useful  in  aortic  as  in  mitral  disease  :  nevertheless, 
when  the  heart-muscle  fails,  and  the  hypertrophy  is  not  compensatory, 
the  drug  is  useful  in  both  aortic  stenosis  and  insufficiency. 

From  the  considerations  which  have  been  brought  forward,  it  is  very 
evident  that  a  knowledge  of  the  relation  of  the  heart-muscle  to  the  work 
required  of  it  in  any  individual  case  is  much  more  necessary  to  the  thera- 
peutist than  to  know  what  valve  is  diseased. 


CARDIAC   STIMULANTS.  325 

In  "irritable  heart"  of  soldiers — a  disease  or  condition  of  cardiac 
irritability  evidently  connected  with  muscular  weakness,  and  very  prob- 
ably dependent  upon  exhaustion  of  the  inhibitory  nerves — Da  Costa" 
found  that  in  the  early  stages  of  the  affection  digitalis  not  only  acted 
better  than  any  other  remedy,  but  even,  when  administered  continuously 
for  some  time,  often  effected  a  permanent  cure.  When  hypertrophy  had 
taken  place,  the  drug  was  of  little  use. 

The  relief  afforded  by  digitalis  in  not  too  inveterate  cardiac  disease 
is  often  in  a  measure  permanent,  because  the  drug  may  aid  very  materi- 
ally in  the  production  of  compensatory  hypertrophy.  Dilatation  is  cer- 
tainly more  apt  to  occur  when  the  muscular  fibre  is  lax  and  acting  feebly 
than  when  it  is  toned  up  and  in  vigorous  play  ;  secondly,  the  stimulus  to 
action  in  a  muscle  is  almost  of  necessity  directly  or  indirectly  a  stimulus 
to  its  nutrition  ;  thirdly,  it  appears  probable'  from  the  researches  of  Gas- 
kell  that- the  period  of  inhibition  is  one  of  structural  upbuilding,  and  that 
therefore  the  pneumogastric  nerve  is  trophic  in  its  nature,  so  that  it  is 
probable  that  digitalis,  by  stimulating  the  trophic  cardiac  nerve,  benefits 
the  cardiac  nutrition  ;  lastly,  improved  systemic  circulation  means  in  a  far 
more  intense  degree  improved  blood-supply  to  the  cardiac  muscle,  as  is 
shown  by  the  following  considerations. 

During  systole  the  cardiac  muscle  contracts  so  as  completely  to 
squeeze  out  all  the  venous  blood  from  the  heart- walls.  The  arterial  blood 
enters  during  diastole,  and  the  force  which  drives  it  into  the  relaxed  walls 
is  derived  from  the  arterial  system.  The  coronary  arteries  arise  nearly 
at  a  right  angle  to  the  aorta  :  the  blood  squirts  into  the  latter  during  sys- 
tole in  an  unbroken  stream,  and  probably  does  not  enter  freely  the  coro- 
nary artery.  But  when  the  reflux  wave  comes,  the  aortic  valve  flaps  to, 
and  the  whole  pressure  of  the  blood-column  forces  the  liquid  into  the 
open  cardiac  arteries.  If  the  arterial  system  be  emptied,  or  nearly  so, 
the  arteries  are  not  distended  sufficiently  to  give  origin  to  a  powerful  re- 
flux wave,  and  but  little  blood  enters  the  coronary  artery, — i.e.,  the  cardiac 
walls.  The  dilated  feeble  heart  is  unable  during  systole  thoroughly  to 
free  its  walls  of  venous  blood,  and  during  diastole  the  force  is  lacking  for 
driving  in  the  arterial  blood.  Digitalis  enables  the  cardiac  muscle  com- 
pletely to  free  itself  of  venous  blood,  and  at  the  same  time,  by  restoring 
to  a  greater  or  less  degree  the  normal  balance  of  the  circulation  and  re- 
moving the  excess  of  blood  from  the  general  venous  system,  gives  the 
aorta  sufficient  blood  to  provoke  an  active  reflux.* 


*  We  have  let  this  paragraph  stand  as  in  previous  editions,  although  the  experiments 
of  Martin  seem  to  show  that  the  circulation  is  most  active  in  the  heart's  wall  during  sys- 
tole. The  appearance  of  the  wall  of  a  diastolic  heart  as  contrasted  with  that  of  a  systolic 
heart  makes  one,  however,  loath  to  admit  the  conclusion  that  the  blood  enters  the  mus- 
cles as  freely  during  systole  as  in  the  first  period  of  diastole.  Moreover,  even  if  Martin's 
vie\v  were  adopted,  the  therapeutic  reasoning  would  have  to  he  changed  in  wording  only, 
not  in  drift ;  the  facts  remaining  that  the  heart-muscle  feels  most  powerfully  failure  of 
arterial  circulation,  and  that  therefore  cardiac  overwork  and  starvation  are  apt  to  go  hand 
in  hand,  so  that  the  relief  of  the  circulation  by  the  digitalis  may  bring  about  perma- 
nent nutritive  changes  in  the  heart-muscle. 


326  GENERAL  REMEDIES. 

That  digitalis  exerts  the  nutrient  and  trophic  influence  here  set  forth 
has  been  strongly  confirmed  by  the  research  of  Hare  and  Coplin,85  in 
which  it  was  found  that  the  continuous  giving  of  digitalis  to  young  pigs 
produced  a  distinct  increase  in  the  size  and  weight  of  the  heart  as  con- 
trasted with  control  animals  of  the  same  litter. 

If  in  aneurism,  or  in  general  capillary  atheroma,  there  be  increased 
resistance  to  the  circulation,  and  the  heart  have  not  sufficient  power  to 
meet  this,  digitalis  may  be  useful,  but  must  be  employed  with  caution. 
It  not  only  increases  arterial  pressure,  but  also  causes  the  pulse-wave  to 
be  of  enormous  size  as  well  as  power,  so  that  there  is  great  danger  of 
distending  and  tearing  open  the  thinned  wall  of  an  aortic  aneurism.  The 
use  of  digitalis  for  the  purpose  of  ' '  quieting  the  circulation' '  in  aneurism 
is  very  dangerous.  We  have  seen  immediately  fatal  hemorrhage  pro- 
duced thereby. 

In  cardiac  dropsy  digitalis  is  of  service  probably  not  only  by  regu- 
lating through  the  heart  the  circulation,  and  by  evacuating  the  surplus 
fluid  through  the  kidneys,  but  also  by  an  action  upon  the  vessels,  vaso- 
motor  weakness  being  evidently  a  strong  factor  in  the  production  of  dropsy. 

In  endocarditis  and  in  myocarditis  with  marked  irregularity  of  the 
cardiac  action  and  failing  power  there  is  naturally  a  strong  impulse  to 
the  administration  of  digitalis.  It  should  be  remembered,  however,  that 
in  an  acute  inflammation  of  the  lining  membrane  of  the  heart  the  action, 
of  the  heart  is  often  really  of  the  nature  of  an  excitement,  and  that,  there- 
fore, it  would  a  priori  be  expected  that  digitalis  would  do  harm  rather 
than  good.  Restrained  by  this  belief,  we  have  never  used  digitalis 
boldly  in  this  condition,  but  from  the  doses  given  have  failed  to  per- 
ceive any  good  effect.  In  the  after-stages  of  an  endocarditis,  when  the 
heart  is  troubled  with  recent  patency  of  valve,  digitalis  is  a  remedy  of 
the  very  greatest  importance,  often  relieving  the  symptoms  distinctly 
and  very  strongly  favoring  the  development  of  that  compensatory  hyper- 
trophy in  which  lies  the  only  hope  of  the  patient.  During  the  exhibition 
of  the  digitalis,  however,  the  patient  should  be  closely  watched,  and  any 
evidence  either  of  overaction  of  the  drug  or  of  overgrowth  of  the  heart 
should  lead  to  the  suspension  of  the  remedy. 

In  acute  myocarditis  digitalis  is  commonly  absolutely  inefficient. 
How  far  its  action  upon  the  muscle  itself  will  render  it  harmful  is  at  pres- 
ent unknown. 

These  statements  are  so  correct  that  in  cases  of  rapid  degeneration  of 
the  muscles  from  diseases  of  the  coronary  artery  the  effect  of  digitalis 
can  sometimes  be  made  available  for  diagnostic  purposes.  When  the 
symptoms  point  strongly  to  coronary'  artery  diseases,  and  digitalis  freely 
given  fails  to  exert  any  perceptible  influence  upon  the  heart,  the  progno- 
sis is  most  grave. 

Digitalis  in  large  doses  is  a  valuable  cardiac  stimulant  in  syncope  or 
sudden  collapse  from  hemorrhage  or  other  cause.  To  overcome  its  slow- 
ness of  action  we  have  used  it  hypodermically  often  with  excellent  effects. 


CARDIAC   STIMULANTS.  327 

From  twenty  to  thirty  minims  of  the  tincture  should  be  injected  into  the 
arm,  and  repeated  in  half  an  hour  if  absolutely  necessary,  or  a  grain  of 
digitalin  may  be  substituted.  In  our  experience*  digitalin  has  several 
times  given  rise  to  severe  local  irritation,  the  tincture  very  rarely. 

In  many  cases  of  general  debility  or  so-called  neurasthenia,  although 
there  may  be  no  disease  of  the  organs  especially  concerned  in  the  circu- 
lation, the  latter  is  exceedingly  feeble,  and,  as  a  consequence,  all  portions 
of  the  system  are  imperfectly  supplied  with  blood.  Under  these  circum- 
stances preparations  of  digitalis  are  very  useful  as  general  tonics. 

A  number  of  eminent  physicians  assert  that  they  have  obtained  excel- 
lent results  by  the  use  of  half  an  ounce  of  the  tincture  of  digitalis  in  the 
treatment  of  delirium  tremens,  especially  in  those  cases  in  which  the 
pulse  is  very  soft  and  feeble.  The  evidence  of  the  value  and  safety  of 
the  remedy  in  such  cases  is  too  strong  to  be  overlooked,  but  does  not 
indicate  the  possession  of  narcotic  properties  by  the  drug.  The  rest 
and  sleep  which  have  followed  the  administration  have  probably  been 
the  result  of  the  cardiac  stimulation  and  the  increased  flow  of  blood  to 
the  nerve-centres.  Enormous  doses  of  digitalis  are  tolerated  in  these 
cases,  probably  because  the  heart  has  become  by  long  habit  very  much 
benumbed  to  the  influence  of  stimulants.  Their  use  is  not,  however, 
entirely  free  from  danger. 

Digitalis  is  a  very  important  remedy  in  the  treatment  of  poisoning 
by  such  substances  as  muscarine,  delphinine,  aconite,  and  the  nitrites, 
which  have  been  proved  to  be  directly  antagonistic  to  it  in  their  action 
upon  the  heart. 

Dobie w  reports  a  case  of  recovery  after  the  ingestion  of  an  ounce  of  Flem- 
ing's  tincture  of  aconite,  apparently  due  to  the  hypodermic  injection  of  twenty 
minims  of  tincture  of  digitalis  and  the  exhibition  by  the  mouth  of  three  doses  in  an 
hour  of  a  mixture  of  tincture  of  digitalis  (one  drachm  each  dose),  brandy,  and 
ammonia. 

Digitalis  is  often  of  great  value  in  various  acute  diseases,  f  such  as 
adynamic  pneumonia  and  adynamic  fevers,  by  maintaining  the  heart' s 
action.  It  can  have  no  effect  upon  the  diseases  themselves,  but  may  help 
most  opportunely  to  sustain  the  heart  during  a  crisis  or  a  period  of  strain 
upon  it.  When  in  any  form  of  pneumonia  \  the  right  heart  is  yielding  to 
the  strain  of  forcing  blood  through  pulmonic  capillaries  pressed  upon  and 
reduced  in  their  aggregate  lumen  by  exudation,  digitalis  may  be  of 
service. 

*  Local  irritation,  and  even  the  production  of  abscesses,  have  also  been  noted  by 
various  observers  besides  ourselves.  See  Witkowski  (Deutsches  Archivf.  Klin.  Med., 
xviii.  142) ;  also  Pel  (Centralb.f.  Med.  Wiss.,  1877,  169). 

t  Consult  Hankel  (British  and  Foreign  Medico- Chirurgical  Review,  xxxi.  513), 
Grimshaw  (Dublin  Quarterly,  June,  1873),  and  Anstie  (London  Practitioner,  September, 

1873)- 

J  According  to  the  experiments  of  F.  Badano  (A.  I.  B.)  the  normal  toxicity  of  blood- 
serum  and  of  urine  diminishes  very  greatly  in  pneumonia,  but  is  in  large  measure  re- 
stored under  the  action  of  digitalis. 


328  GENERAL  REMEDIES. 

With  the  idea  that  digitalis  is  an  active  antipyretic,  it  has  been  pre- 
scribed in  various  acute  diseases,  sometimes  with  asserted  good  results. 
As  already  stated,  toxic  doses  of  digitalis  at  first  elevate  the  temperature  ; 
and  proof  is  wanting  that  in  healthy  men  therapeutic  doses  have  any 
decided  influence  in  depressing  the  temperature.  There  seems  to  be, 
therefore,  no  good  physiological  basis  for  the  antipyretic  use  of  digitalis  ; 
at  the  same  time,  it  is  very  possible  that  it  may  directly  or  indirectly 
lower  the  temperature  in  disease.  Clinical  proof  of  this  is,  however, 
still  wanting.  The  strongest  evidence  in  favor  of  such  action  is  fur- 
nished by  the  records  of  Wunderlich,37  according  to  which  from  half  a 
drachm  to  a  drachm  of  digitalis,  given  in  divided  dose  during  three  or 
four  days  in  the  second  or  third  week  of  severe  typhoid  fever,  imme- 
diately produces  a  slight  fall  of  temperature  in  a  large  proportion  of  the 
cases,  and  sometimes  a  considerable  fall.  This  fall  is  said  not  to  last 
more  than  a  day,  when  the  temperature  rises  again,  but  in  cases  favorably 
affected  does  not  regain  the  original  height  ;  the  pulse  is  very  much  low- 
ered in  frequency,  and  remains  about  uniform  for  four  days.  It  is  evi- 
dent that  at  least  in  some  of  these  cases  of  Wunderlich' s  the  drug  was 
given  about  the  time  natural  defervescence  would  be  expected  to  occur, 
and  that  the  slight  reduction  of  temperature  brought  about  at  such  time 
does  not  argue  very  strongly  in  favor  of  the  proposition  that  digitalis  is 
a  powerful  antipyretic  in  disease.  Far  more  extensive  and  complete 
observations  must  be  made  upon  a  rising,  not  a  falling,  temperature 
before  any  satisfactory  conclusion  can  be  reached.  At  present  the 
antipyretic  use  of  digitalis  should  be  purely  tentative.  In  puerperal 
fever  Winkel 3S  believes  that  digitalis  does  good  by  its  action  on  the 
heart,  by  contracting  the  arterioles  of  the  uterus,  and  by  lowering  tem- 
perature. 

The  property  of  causing  contraction  of  all  unstriped  muscular  fibres 
has  been  attributed  to  digitalis,  but,  while  the  probabilities  are  certainly 
such  as  to  invite  investigation,  we  have  no  definite  knowledge  upon  the 
subject.  Dickenson  M  asserts  that  it  has  a  powerful  action  in  causing  the 
uterus  to  contract  and  to  arrest  hemorrhage, — in  menorrhagia,  a  few 
minutes  after  an  ounce  and  a  half  of  the  infusion  is  swallowed,  severe 
pains  resembling  those  of  the  first  stage  of  labor  coming  on,  with  a  mo- 
mentary profuse  discharge  of  blood  and  clots,  if  there  be  any  present, 
followed  by  arrest  of  the  flow  for  hours.  Stadion40  states  that  digitalis 
is  capable  of  temporarily  but  completely  annulling  the  activity  of  the 
sexual  organs,  and  that  it  may  be  regarded  as  a  true  anaphrodisiac. 
M.  Gaunot "  makes  the  same  assertion,  and  advises  the  use  of  the  drug 
in  spermatorrhoea. 

The  use  of  digitalis  as  a  diuretic  will  be  considered  under  that 
heading. 

TOXICOLOGY. — In  poisoning  by  digitalis,  the  first  symptom  of  any 
severity  is  generally  vomiting  of  mucus  and  bile,  very  violent  and  very 
often  repeated.  At  the  same  time  a  feeling  of  heat  of  the  head,  dis- 


CARDIAC   STIMULANTS.  329 

ordered  vision,  and  vertigo  manifest  themselves.  The  pulse  at  this  time 
in  the  horizontal  position  may  be  full  and  strong  and  slow,  but  on  the 
patient's  rising  becomes  weak  and  rapid.  The  face  is  pale.  The  vomiting 
continuing,  profound  prostration  comes  on,  and  the  pulse  becomes  feeble, 
small,  and  irregular,  although  the  beat  of  the  heart  may  be  strong  and  hard. 
The  eyes  are  very  prominent,  the  pupils  fixed  and  dilated  :  *  according  to 
Tardieu,  an  almost  diagnostic  symptom  is  the  blue  color  of  the  sclerotic. 
Abundant  salivation  sometimes  occurs.  Intense  headache  and  pains  in 
the  back  or  limbs  are  often  complained  of.  Diarrhoea  is  very  generally 
present ;  the  urine  may  be  suppressed.  The  intelligence  is  often  perfect 
in  the  midst  of  profound  collapse,  but  delirium  more  or  less  violent 
finally  comes  on.  Death,  usually  preceded  by  stupor  or  by  convulsions, 
takes  place  most  frequently  in  one  or  two  days,  but  has  occurred  as  late 
as  the  tenth  day  and  as  early  as  three-quarters  of  an  hour.f 

H.  O.  Hall,42  in  accordance  with  the  previous  statements  of  Doroziez 
and  other  French  writers,  states  that  when  given  only  in  full  medicinal 
doses  digitalis  may  produce  hallucinations  and  even  violent  delirium. 
Such  result  must,  however,  be  an  extremely  rare  phenomenon. 

In  the  majority  of  cases  of  digitalis-poisoning  the  patient  recovers. 
When  this  happens,  the  symptoms  gradually  ameliorate.  Cardiac  weak- 
ness, and  even  a  bruit  de  souffle,  with  more  or  less  exophthalmos,  \  are  said 
to  have  persisted  for  weeks  in  some  cases.  In  poisoning  by  digitalin  the 
symptoms  are  those  of  rapid  digitalis-poisoning, — violent  vomiting,  intense 
cephalalgia,  and  sometimes  rachialgia,  irregular,  feeble,  intermittent  pulse, 
and  paroxysms  of  suffocation. 

The  minimum  fatal  dose  of  digitalis  is  not  known. 

A  large  teaspoonful  of  the  tincture  is  said  to  have  caused  alarming  symptoms 
in  a  young  puerperal  woman  (Tardieu,43  Obs.VIII.)  ;  twenty  grains  of  the  extract 
proved  fatal  on  the  tenth  day  (Tardieu,  Obs.  VI.),  and  two  and  a  half  grammes  of 
the  leaves  in  infusion  on  the  fifth  day  (Tardieu,  Obs.  X.)  ;  fifty  granules  (one-fiftieth 
of  a  grain  each  ?)  of  digitalin  have  been  recovered  from  (Tardieu,  Obs.  XII.,  XIV. )  ; 
about  one-fourth  of  a  grain  of  digitalin  u  produced  very  violent  but  not  lethal  symp- 
toms. In  the  only  fatal  case  of  digitalin-poisoning  we  know  of  ( Affaire  Couty  de  la 
fomerrais),  the  amount  ingested  was  unknown.  In  a  case  reported  by  Frank 
Radcliffe,  one-twentieth  of  a  grain  of  Nativelle1  s  digitalin  is  said  to  have  caused 
vomiting,  profuse  sweating,  feeble,  irregular,  intermittent  pulse,  shallow  and  slow 
respirations,  coma,  ending  in  recovery. 

*  Hauber  (Munch.  Mcd.  U'ochensch.,  1890)  details  a  case  of  death,  due,  according 
to  his  belief,  to  digitalis-poisoning,  with  contraction  of  the  pupils. 

t  See  case  reported  by  M.  Earth  (quoted  by  Tardieu).  In  a  case  of  poisoning  by  ten 
grammes  of  tincture  of  digitalis,  said  to  contain  twenty  milligrammes  of  digitalin,  the 
symptoms  were  vomiting,  great  pain  in  the  head,  prostration,  a  very  small  pulse, — 40 
per  minute, — anuria,  and  a  systolic  bruit  heard  over  the  whole  heart,  having  its  maximum 
intensity  at  the  base.  Recovery  occurred  in  two  days  (Mem.  Soc.  de  Mcd.  de  Bordeaux, 
1884,  397). 

t  As  was  first  noticed  by  Lauder  Brunton,  in  dogs  poisoned  with  digitalis  a  blowing 
systolic  murmur  may  be  at  times  heard,  due  to  an  irregular  action  of  the  papillary 
muscles. 


330  GENERAL  REMEDIES. 

The  treatment — after  the  evacuation  of  the  stomach  and  bowels,  and 
the  very  free  administration  of  tannic  acid  (as  the  best,  although  unre- 
liable, chemical  antidote) — should  consist  in  the  exhibition  of  opium, 
strychnine,  and  alcoholic  stimulants,  with  rest  in  the  horizontal  position. 
We  know  of  no  recorded  experiences  with  the  antagonistic  poisons  to 
digitalis,  such  as  aconite  or  muscarine. 

E.  Zugsmith 4i  reports  a  case  of  violent  cumulative  action  of  digitalis  in  an 
infant,  in  which,  acting  upon  the  theory  that  fever  overcomes  the  cardiac  influence 
of  digitalis,  he  exposed  the  child  to  high  temperature  in  a  vapor  bath  at  120°  F., 
with  immediate  relief  of  the  symptoms.  After  sixty  hours  the  symptoms  had 
sufficiently  disappeared  to  allow  the  removal  of  the  child  from  the  bath. 

Two  cases,  one  ending  fatally,  of  what  may  be  considered  chronic 
digitalis-poisoning  have  been  reported  by  Kohnhorn.4*  The  symptoms 
were  loss  of  appetite,  tinnitus  aurium,  vertigo,  lowering  of  the  rate  and 
force  of  the  pulse,  diarrhoea,  weakness,  general  anaemia,  and  syncopal 
attacks.  The  only  lesion  found  at  the  autopsy  was  congestion  with 
ecchymosis  of  the  gastro-intestinal  mucous  membrane. 

ADMINISTRATION. — Digitalis  may  be  given  in  substance  in  the  form 
of  pills  ;.  the  dose  being  one  grain  three  times  a  day,  increased  until 
some  effect  is  produced.  The  solid  extract  (EXTRACTUM  DIGITALIS, 
U.  S. )  is  less  reliable  than  the  leaves  ;  its  dose  is  one-fourth  of  a  grain 
(0.016  Gm. ).  When  a  rapid  action  is  desired,  one  of  the  following  official 
preparations,  or  German  digitalin,  should  be  used  :  INFUSUM  DIGITALIS 
(1.5  per  cent.), — dose,  one  fluidrachm  to  half  a  fluidounce  (3.75-15 
C.c.  )  ;  TINCTURA  DIGITALIS  (ten  per  cent. ), — dose,  ten  to  twenty  minims 
(0.3-1.2  C.c.)  ;  FLUIDEXTRACTUM  DIGITALIS,  U.  S. , — dose,  one  to 
two  minims  (0.06-0.12  C.c.). 

In  emergencies  where  single  doses  are  administered  they  may  be 
very  much  larger  than  those  here  given.  Thus,  of  the  tincture,  two 
fluidrachms  or  even  half  an  ounce  may  be  exhibited  ;  of  the  infusion,  a 
wineglassful.  Moreover,  in  desperate  cases,  the  physician  is  justified  in 
taking  the  risk  of  the  administration  of  repeated  very  large  doses  of 
digitalis.  We  have  seen  a  number  of  cases  of  excessively  severe  chronic 
cardiac  failure,  with  Cheyne-Stokes  respiration,  orthopncea,  and  almost 
absolute  insomnia,  in  which  the  administration  of  half  a  drachm  or  a 
drachm  of  the  tincture  of  digitalis  three  or  four  times  a  day  has  enabled 
the  patient  to  resume  for  a  time  the  ordinary  duties  of  life.  In  almost 
every  case  of  this  character  which  we  have  watched,  death  has  finally 
come  by  sudden  syncope,  while  the  patient  was  still  going  about  and 
enjoying  a  comfortable  life.  We  do  not  believe  that  the  arrest  of  the 
cardiac  action  has  been  due  to  a  direct  action  of  the  drug,  but  to  the 
fact  that  the  enormous  doses  have  stimulated  the  heart  and  steadied 
its  expenditure  of  force,  so  that  it  was  enabled  to  go  on  until  the  last 
particle  of  cardiac  vital  power  was  exhausted.  H.  C.  Wood  further 
says  that  in  an  experience  of  forty-four  years  in  which  he  has  used 


CARDIAC   STIMULANTS.  33* 

digitalis,  frequently  in  enormous  doses,  he  has  seen  but  one  case  in 
which  he  thought  it  did  serious  harm  by  a  toxic  action.  The  infusion 
of  digitalis  is  believed  by  many  practitioners  to  be  more  active  than  the 
tincture.  This  is  simply  because  the  infusion  is  commonly  used  in  much 
larger  doses  than  the  tincture.  Either  preparation  is  efficient  if  properly 
made  from  fresh  leaves. 

When  digitalis  is  administered  persistently,  its  first  evident  influence 
may  be  suddenly  developed  after  long  delay."  It  is  said  that  sometimes 
the  first  marked  symptom  of  this  so-called  ' '  cumulative  action' '  is  severe 
syncope,  followed  by  paraplegia,  vomiting,  diarrhoea,  delirium,  general 
insensibility,  and  death.  Such  cases  must  be  extremely  rare  :  usually  a 
sudden  drop  of  the  pulse  is  the  most  serious  effect,  provided  that  the 
administration  of  the  remedy  be  at  once  suspended.  It  is  a  matter  of  much 
importance  to  determine  when  this  cumulative  action  is  to  be  expected. 
It  is  probably  connected  with  slow  absorption  and  elimination,  and  is 
much  more  prone  to  occur  when  there  is  no  diuretic  effect.  It  is  also 
very  apt  to  appear  after  tapping  :  the  sudden  removal  of  pressure  from 
the  vessels  leads  to  the  picking  up  from  the  tissues  of  serum, — saturated, 
it  may  be  with  digitalis  principles, — and  also  to  the  rapid  absorption  of 
any  digitalis  which  may  be  in  the  alimentary  canal. 

In  a  very  elaborate,  careful  research,  Fraenkel49  has  found  that  digitalis  gluco- 
sides  have,  when  given  continuously  to  the  lower  animals,  a  very  distinct  tendency 
to  cumulative  action,  and  to  a  sudden  passage  of  the  therapeutic  over  into  the  toxic 
effect.  The  tendency  of  this  influence  was  much  greater  with  digitoxin  than  with 
digitalinum  verum  ;  indeed,  Fraenkel  found  it  very  difficult  to  experimentally  produce 
marked,  continued  slowing  of  the  pulse  with  digitoxin  without  causing  fatal  poison- 
ing. For  the  reason  that  Heide  and  also  Stokvis  have  shown  that  the  very  soluble 
helleborein,  and  because  he  himself  has  determined  that  soluble  strophanthin  has  a 
marked  tendency  to  cumulative  action,  Fraenkel  believes  that  this  action  is  due  to 
such  permanence  of  union  between  the  glucosides  and  the  heart  tissue  that  the 
muscle  refuses  to  give  up  the  glucoside  to  the  process  of  elimination,  and  continu- 
ally adds  the  new  secretion  to  itself. 

In  the  experiments  of  Frsenkel,  digitoxin  was  found  to  be  an  extremely  danger- 
ous remedy  in  the  lower  animals.  It  was  also  made  out  that  0.08  milligramme 
was  the  toxic  equivalent  of  0.48  of  digitalinum  verum  ;  so  that,  as  far  as  physiological 
experimentation  goes,  digitalinum  verum  was  found  to  be  much  safer  and  much 
more  prompt  in  its  action  than  digitoxin. 

T.  Lauder  Brunton  and  J.  Theodore  Cash  **  find  that  high  tempera- 
ture so  affects  the  cardiac  inhibitory  apparatus  in  the  cat  that  it  will  not 
respond  to  digitalis,  and  believe  that  high  temperature  greatly  interferes 
with  the  action  of  digitalis.  In  this  they  are  abundantly  sustained  by 
general  clinical  experience  ;  very  commonly  in  high  fever  it  seems  almost 
impossible  to  obtain  the  digitalis  pulse.*  In  pneumonia  and  other  diseases 

*  It  is  probable  that  all  active  poisons  are  greatly  influenced  by  high  temperature.  It 
is  said  that  in  order  to  cause  the  death  of  dogs  suffering  from  septic  fever,  fifteen  to  thirty 
per  cent,  beyond  the  ordinary  fatal  dose  of  the  following  poisons  is  required  :  strychnine, 
curara,  morphine,  atropine,  nicotine,  veratrine,  digitaline,  hell«borein,  chloral,  formal- 
dehyde, sodium  nitrite,  cobalt,  nickel  chloride,  iron  chloride.  (See  Arch,  di  Farmacol. 
e  Terap.,  viii.  1900.) 


332  GENERAL   REMEDIES. 

with  high  temperature  and  a  sudden  defervescence  some  care  should  be 
exercised  in  the  very  bold  use  of  the  remedy,  lest  when  the  temperature 
suddenly  falls  inordinate  digitalis  effects  may  appear.  Fear  of  the  cumu- 
lative action  of  digitalis  should  not  interfere  with  its  persistent  adminis- 
tration in  cases  of  cardiac  or  other  disease  in  which  it  is  indicated,  but 
should  lead  the  practitioner  to  interrupt  its  use  at  intervals  so  as  to  allow 
the  clearance  of  the  system. 

If  a  representative  of  digitalis  in  small  bulk  be  desired,  probably  the 
best  preparation  is  Merck's  German  digitalin.  This  preparation  has  been 
deemed  uncertain,  but,  according  to  the  clinical  reports  of  Beates 50  and  the 
experiments  of  Arnold  and  Wood,  this  is  because  it  has  been  habitually 
given  in  absurdly  small  dose.  According  to  the  closely  agreeing  results 
of  these  investigators,  one-quarter  of  a  grain  (0.015  Gm.  )  is  about  equiva- 
lent to  fifteen  minims  of  the  tincture,  and  represents  the  full  therapeutic 
value  of  digitalis.  The  dose  was  formerly  considered  one-fiftieth  to  one- 
thirtieth  of  a  grain  (0.0013-0.002  Gm. ).  It  seems  to  be,  however, 
equally  as  irritant  as  the  tincture,  and  offers  no  distinct  advantage  except 
its  small  bulk. 

Digitoxin,  according  to  the  experiments  of  J.  P.  Arnold  and  H.  C. 
Wood,  Jr.,51  of  Zeltner,52  of  Curioni,53  affects  the  circulation  of  the  lower 
animals  as  does  German  digitalin  or  digitalis.  The  tendency  of  it  to  act 
cumulatively,  so  marked  in  the  experiments  made  by  Fraenkel,  has  been 
confirmed  by  Arnold  and  H.  C.  WTood,  Jr.,  and  clinically  by  Zeltner. 
Digitoxin  is  locally  very  irritant,  and  is  probably  at  least  as  prone  as  is 
digitalis  to  derange  the  digestion,  although  Penzoldt54  claims  that  gastric 
irritation  may  be  evaded  by  giving  the  glucoside  only  when  the  stomach 
is  full.  The  dose  of  digitoxin  must  at  present  be  considered  as  unset- 
tled, but  one-quarter  of  a  milligramme  may  be  used  with  entire  safety. 

Zeltner  considers  that  one-quarter  of  a  milligramme  (^^  Gr. )  is  equivalent  to 
0.235  grammes  (3!  Grs. )  of  powdered  digitalis  ;  or,  in  other  words,  that  digitoxin 
is  about  one  thousand  times  stronger  than  the  crude  drug.  Bosse 5b  considers  one 
milligramme  of  digitoxin  as  equal  to  one  gramme  of  digitalis  ( i  to  1500  leaves),  and 
has  used  the  glucoside  by  enema  up  to  two  and  one-half  milligrammes  a  day  with 
excellent  results.  Curioni  gives  the  minimum  ordinary  single  dose  as  one-half  a 
milligramme  (Ti-Q  Gr. ),  the  maximum  at  one  milligramme. 

Hypodermic  Administration. — When  it  is  desired  to  use  digitalis 
hypodermically  the  tincture  is  the  preparation  commonly  preferred,  and 
in  our  experience  it  causes  less  irritation  than  do  solutions  of  digitalin. 
It  is  claimed  by  D.  E.  Hughes  M  that  if  the  tincture  be  so  prepared  as  to 
be  free  from  fatty  substances  it  is  hypodermically  non-irritant.  The 
hypodermic  use  of  the  active  principles  of  digitalis  must  at  present  be 
considered  as  tentative. 

Huchard  "  affirms  that  by  means  of  gentle  warmth  an  oily  solution  of  Nativelle's 
digitalin  can  be  made,  which,  when  given  hypodermically,  acts  efficiently,  and  does 
not  cause  local  irritation, — dose,  not  to  exceed  one-sixty-fifth  of  a  grain.  It  is  stated 


CARDIAC   STIMULANTS.  333 

by  Madsen,  of  Copenhagen,  that  one  cubic  centimetre  (16  M. )  of  so-called  Petit's 
solution  will  dissolve  one  milligramme  (fa  Gr. )  of  digitoxin.  Of  such  a  liquid  four 
minims  (2\-e  Gr. )  is  the  hypodermic  dose.  Petit  s  solution  :  Glycerin,  333  parts  ; 
alcohol,  95  parts  ;  water  to  1000  parts. 

APOCYNUM.     U   S.— CANADIAN    HEMP. 

Of  the  two  indigenous  members  of  the  Apocynum  family  the  United 
States  Pharmacopoeia  recognizes  the  root  of  the  Apocynum  Cannabinnm. 

ACTIVE  PRINCIPLE. — Schmiedeberg J  has  separated  from  apocynum 
two  principles,  to  which  he  gave  the  name  of  apocynin  and  apocynein. 
The  latter  is  a  glucoside,  while  the  precise  nature  of  apocynin  he  did  not 
determine.  According  to  H.  C.  Wood,  Jr.,  the  substance  furnished  by 
Merck  &  Co.  under  the  name  of  apocynin  is  inactive. 

PHYSIOLOGICAL  ACTION. — There  have  been  two  studies  of  the  physi- 
ological action  of  apocynum,  one  by  Dotschewski 2  and  the  other  by  H. 
C.  Wood,  Jr.3  In  both  these  researches  it  was  shown  that  the  drug  has 
an  effect  on  the  circulation  similar  to  that  of  digitalis,  causing  a  marked 
rise  of  the  blood-pressure  with  slowing  of  the  pulse,  followed,  when  the 
dose  has  been  sufficiently  large,  by  a  marked  increase  in  the  rate  of  the 
pulse  and  a  sudden  cessation  of  the  heart's  action.  Both  of  these  inves- 
tigators agree  that  the  slowing  of  the  pulse  does  not  occur  after  division 
of  the  pneumogastric  nerves,  and  it  is  therefore  probably  due  to  the  stim- 
ulant effect  upon  the  inhibitory  centres.  According  to  Dotschewski  the 
elevation  of  the  blood-pressure  is  largely  dependent  upon  stimulation  of 
the  vaso-motor  centres.  In  the  experiments  of  H.  C.  Wood,  Jr.,  how- 
ever, section  of  the  spinal  cord  did  not  lessen  the  power  of  apocynum  to 
cause  an  elevation  of  the  blood-pressure,  and  this  observer  attributes  the 
elevation  of  the  pressure  either  to  stimulation  of  the  cardiac  muscle,  or  a 
stimulation  of  the  arterial  walls  directly,  or  both.  Since  both  investigators 
agree  that  there  is  a  contraction  of  the  vessels  of  the  kidney,  it  seems 
probable  that  there  is  a  stimulant  influence  directly  upon  the  arterial  walls. 
The  character  of  the  pulse-wave  after  the  injection  of  this  drug  and  the 
fact  that  the  heart's  action  is  arrested  in  systolic  spasm,  as  after  digitalis, 
renders  it  probable  that  the  elevation  of  the  blood-pressure  is  due  to 
simultaneous  stimulation  of  the  heart  and  of  the  vascular  system. 

During  the  stage  of  rapid  pulse  electrical  irritation  of  the  vagus  fails  to 
slow  the  pulse,  indicating  that  there  is  probably  a  late  paralysis  of  the 
peripheral  ends  of  the  inhibitory  nerves  of  the  heart. 

Secretion  of  Urine.  — According  to  Dotschewski  a  large  dose  of  apocy- 
num causes  such  a  marked  constriction  of  the  kidney  vessels  in  the  normal 
animal  as  to  greatly  lessen  the  flow  of  urine  and  may  cause  complete  arrest 
of  this  secretion.  When,  however,  there  has  been  a  failure  of  renal  activity 
brought  about  through  the  injection  of  a  depressant  drug  as  chloral,  apo- 
cynum causes  a  re-establishment  of  the  urinary  secretions. 

Nervous  System. — The  action  of  apocynum  upon  the  nervous  system 
is  certainly  a  very  feeble  one  since  Wood,  Jr.,  found  in  the  frog  that  after 


334  GENERAL  REMEDIES. 

a  dose  sufficient  to  cause  complete  arrest  of  the  heart  there  is  still  left 
some  voluntary  and  reflex  power,  and  that  the  motor  nerve  remains  irrita- 
ble for  some  time  after  death. 

THERAPEUTICS. — The  original  observation  of  Knapp  that  apocynum 
is  a  valuable  diuretic  in  cases  of  dropsy,  especially  when  dependent  upon 
hepatic  cirrhosis,  has  been  confirmed  by  Griscom,4  Dabney,5  and  many 
other  observers.  Lowry 6  has  also  found  the  drug  of  value  to  aid  in  the 
elimination  of  fluid  accumulating  as  the  result  of  various  cardiac  lesions  as 
well  as  in  chronic  Bright 's  disease. 

The  irritant  effect  of  the  drug  upon  the  mucous  membranes  very 
seriously  interferes  with  its  therapeutic  use.  According  to  Griscom,7  if 
given  in  sufficient  dose  it  is  both  emetic  and  purgative. 

Administration. — The  only  official  preparation  of  apocynum  is  the 
fluid  extract  (FLUIDEXTRACTUM  APOCYNUM,  U.  S. ),  which  may  be 
given  in  doses  of  five  to  fifteen  minims  (0.3-1.0  C.c. ). 

STROPHANTHUS. 

Under  the  names  of  Kombe',  Inee,  Onaye,  Pahouius  poison,  there 
have  reached  Europe  various  African  arrow-poisons,  which  are  now  be- 
lieved to  be  derived  from  one  or  more  species  of  the  tropical  genus  Stro- 
phanthus, — apocynaceous  climbing  shrubs.  The  name  of  Strophanthus 
Kombe"  was  given  by  Sir  John  Kirk  to  the  tree  which  he  first  identified 
as  the  source  of  the  Komb6  poison  ;  but  botanists  are  at  present  agreed 
that  the  species  is  the  Strophanthus  hispidus  of  De  Candolle.  Langgaard 
states  that  there  are  eighteen  species  of  the  genus,  and  that  the  pods  of 
at  least  two  have  entered  commerce.  The  seeds  within  the  pods  are  abun- 
dantly provided  with  very  long  deciduous  hairs,  which  are  apt  to  be  shed 
within  the  pod  itself,  and  are  so  numerous  as  to  weigh  nearly  as  much  as 
the  seeds.  The  seeds  contain  an  intensely  bitter  crystalline  principle,  stro- 
phanthin, which  is  partly  soluble  in  water,  and  has  been  shown  by  T.  R. 
Fraser  to  be  a  glucoside,  convertible  by  sulphuric  acid  into  glucose  and 
crystalline  strophanthidin. 

Local  Action. — Locally,  Strophanthus  and  strophanthin  are  exceedingly 
irritant  to  mucous  membranes.  Strophanthin  is  also  an  anaesthetic,  M. 
E.  Gley *  having  found  that  one-thousandth  of  a  grain  of  strophanthin 
caused  in  the  rabbit's  eye  not  only  a  pronounced  myosis  but  a  very  rapid 
and  durable  anaesthesia.  It  is  true  that  Steinbaugh  concluded  that  this 
anaesthetic  action  is  not  due  to  strophanthin  but  to  some  other  constituent 
of  Strophanthus,  but  Hare  and  De  Schweinitz  have  found  that  in  this 
there  was  some  mistake,  and  that  strophanthin  itself  is  powerfully  anaes- 
thetic, but  is  so  irritant  that  its  application  to  the  eye  may  be  followed  by 
inflammation  or  even  ulceration. 

Absorption  and  Elimination.  — Strophanthus  yields  its  active  principle 
readily  to  absorption  and  elimination.  It  is  therefore  a  promptly  acting 
drug,  but  has  sufficient  permanency  for  the  effects  of  a  single  dose  to  last 
some  hours.  Elimination  is,  however,  probably  too  free  for  any  cumula- 


CARDIAC    STIMULANTS.  335 

tive   effect   like   that  of   digitalis,  since  no  positive  cases  of  such  action 
appear  to  be  on  record. 

General  Action. — In  the  healthy  man  strophanthus  in  sufficient  dose 
produces  fall  in  the  rate  of  the  pulse,  with  increase  of  force,  without 
alteration  of  the  respiration,  but,  if  the  dose  has  been  large  enough,  with 
some  gastric  irritation  and,  according  to  Drasche,  a  slight  fall  of  temper- 
ature. In  Drasche' s  experiments  the  hypodermic  injection  of  fifteen 
drops  of  the  tincture  induced  violent  local  irritation,  repeated  vomiting 
with  nausea,  pronounced  diuresis,  and  a  fall  of  the  pulse.  Twenty  drops 
given  by  the  mouth  decreased  the  pulse  thirty  beats. 

In  the  lower  animals  strophanthus  produces  symptoms  similar  to  those  that  it 
causes  in  man,  the  diarrhoea  often  being  especially  violent.  No  cases  of  human 
poisoning  have  been  reported,  but  after  fatal  poisoning  in  the  lower  animals,  evi- 
dences of  irritation  in  the  gastro-intestinal  tract  are  usually  present,  and  violent 
irritation  and  even  inflammation  of  the  secreting  structure  of  the  kidneys,  with 
small  hemorrhages,  have  been  noted  by  several  observers.  Mairet  and  Combemale 
also  state  that  the  blood-globules  are  frequently  altered,  and  the  urine,  before  death, 
albuminous.  The  absence  of  nervous  symptoms  until  very  late  in  the  poisoning 
shows  how  very  little  influence  strophanthus  has  upon  the  nervous  centres.  An 
observation  upon  the  lower  animals  made  by  Mayeur 2  and  by  Lemoine 3  is  of  great 
practical  interest,  especially  since  similar  results  have  been  obtained  by  some  of 
the  German  authorities  in  man.  These  observers  found  that  strophanthus  has  a 
tendency  to  accumulate  in  the  normal  system,  so  that  when  small  doses  are  given 
daily  for  a  length  of  time,  after  a  time  violent  and  even  fatal  poisoning  results. 

The  first  to  make  elaborate  experiments  with  strophanthus  was  T.  R.  Fraser.4 
One-twentieth  of  a  grain  of  the  extract  of  the  seeds  produced  in  the  frog  stiffness 
of  the  limbs  and  gradual  loss  of  reflexes  and  of  voluntary  movement,  the  respira- 
tion continuing  after  the  cessation  of  the  heart's  beat. 

Nervous  System. — Upon  the  general  nervous  system  strophanthus 
appears  to  have  little  or  no  action.  It  is  true  that  Bahadhurji 5  states 
that  preceding  the  paralysis  there  is  a  stage  of  hypersesthesia,  and  that 
the  motor  nerve-trunks  are  affected  by  the  drug,  but  these  affirmations 
have  not,  that  we  are  aware  of,  been  confirmed. 

Muscles. — The  chief  physiological  influence  of  strophanthus  is  as  a 
muscle-poison.  In  Eraser's  experiments,  the  muscles  of  a  leg  being  pro- 
tected from  the  poisoning  by  tying  the  arteries,  galvanization  of  the 
nerve  caused  active  contractions  at  a  time  when  muscles  elsewhere  failed 
to  respond  to  any  irritation  of  their  nerves  or  substance.  The  first  in- 
fluence of  the  poison  upon  the  muscular  fibre  is  to  increase  its  tonicity, 
and  when  the  muscle  dies  it  does  not  go  into  relaxation,  but  passes 
directly  from  life  into  post-mortem  rigidity. 

Respiration. — Both  Langgaard  and  Fraser  affirm  that  the  fatal  result 
in  poisoning  by  strophanthus  is  due  to  cardiac  arrest,  but  Mairet  and 
Combemale,6  and  also  Bahadhurji  state  that  at  least  in  some  instances 
there  is  a  primary  arrest  of  respiration,  and,  according  to  Mairet  and 
Combemale,  the  respiration  which  is  at  first  hurried  is  usually  distinctly 
slowed  before  the  fatal  termination.  There  is,  however,  no  sufficient 


336  GENERAL  REMEDIES. 

proof  that  the  drug  acts  upon  the  respiratory  centres,  and  though  as- 
phyxial  death  does  occur,  it  is  in  all  probability  the  result  of  the  muscular 
influence  of  the  poison. 

Circulation. — Dr.  Fraser  proved  that  strophanthin  has  a  direct  action 
upon  the  heart  of  the  frog,  and  in  this  has  been  confirmed  by  Bahadhurji, 
by  Huchard,7  by  Reusing,  by  Gley  and  Lapicque,8  and  other  observers. 
By  minute  doses  the  rate  of  the  beat  is  lessened  and  the  size  and  force 
of  the  aortic  pulse-wave  increased. 

The  action  of  strophanthus  upon  the  heart  is  certainly  very  similar  to  that  of 
digitalis,  but  the  assumption  by  some  investigators  that  the  two  influences  are  iden- 
tical does  not  seem  to  us  justified.  Reusing  found  strophanthin  to  be  about  twenty 
times  as  strong  in  its  influence  upon  the  isolated  heart  as  is  digitalin,  and  also 
more  permanent  in  its  effects,  as  the  heart  arrested  by  digitalis  could  be  restored 
by  washing  out  with  fresh  serum,  a  process  which  had  no  influence  when  the  cardiac 
arrest  was  due  to  strophanthin.  It  is  noteworthy  that  Fraser  and  some  other  inves- 
tigators have  found  that  the  frog's  heart  is  arrested  in  systole,  whilst  Reusing  and 
Huchard  have  seen  it  stop  in  diastole,  and  Paul  Bert  has  noted  in  the  cat  both  sys- 
tolic and  diastolic  arrest.  The  muscle  of  the  frog's  heart,  according  to  Fraser,  is 
much  more  susceptible  to  the  influence  of  strophanthin  than  the  voluntary  muscles, 
and  passes  rapidly  into  post-mortem  rigidity,  with  acid  reaction. 

The  combined  testimony  of  Fraser,  of  Popper,9  of  Gley,  of  Paschkis 
and  Zerner,10  of  Langgaard,  and  other  investigators  proves  that  moderate 
doses  of  strophanthus  cause  in  mammals  pronounced  rise  in  the  arterial 
pressure.  As  this  occurs  as  well  in  curarized  (Gley)  as  in  normal  ani- 
mals, it  must  be  due  to  a  direct  action  of  the  drug,  and  not  secondary  to 
changes  in  the  respiration  ;  after  poisonous  doses  the  pressure  immedi- 
ately or  secondarily  falls  gradually  to  zero.  The  sphygmographic  work 
of  Paschkis  and  Zerner  shows  that  strophanthus  influences  the  blood- 
pressure  in  man  as  it  does  in  the  lower  animals.  The  rise  of  blood-press- 
ure is  certainly,  at  least  in  part,  due  to  stimulation  of  the  heart  ;  but  is 
also  to  some  extent  due  to  a  contraction  of  the  blood-vessels  produced 
by  direct  stimulation  of  their  muscle-fibres. 

The  general  muscular  action  of  the  drug  would  indicate  that  it  has  the  power 
of  stimulating  muscle-fibres  in  the  walls  of  the  arterioles,  and  Bahadhurji  asserts 
that  the  vessels  can  be  seen  to  contract  under  its  influence  ;  whilst  Popper  found 
that  section  of  the  splanchnic  nerve  or  of  the  cervical  spinal  cord  does  not  prevent 
the  rise  of  the  arterial  pressure, — a  fact  which  has  been  confirmed  by  Gottlieb  and 
Magnus,16  who  further  demonstrated  with  the  plethysmograph  that  there  is  marked 
contraction  in  the  size  of  the  spleen  evidently  due  to  vascular  contraction.  In  a 
second  research  the  same  observers  found  the  size  of  the  brain  was  increased  rather 
than  decreased  by  strophanthin,  a  change  which  is  probably  the  outcome  of  the 
dominant  influence  of  the  splanchnic-vessels  upon  the  general  blood-pressure. 

The  slowing  of  the  pulse  is  probably  due  to  the  direct  action  of  the 
drug  upon  the  heart,  Paschkis  and  Zerner*  having  found  that  in  the 


*  These  observers  state  that  sometimes  in  the  normal  dog  the  slow  pulse  was  wanting. 


CARDIAC   STIMULANTS.  337 

dog  it  is  not  prevented  by  previous  section  of  the 'vagus  ;  Popper  states 
that  in  the  advanced  poisoning  there  is  peripheral  paralysis  of  the  vagus 
without  alteration  of  the  irritability  of  the  accelerator  nerves. 

Diiiretic  Action. — Although  several  observers  have  failed  to  notice 
an  increase  in  the  urinary  secretion  in  man  and  in  animals  under  the  influ- 
ence of  strophanthus,  yet  the  general  testimony  is  too  strong  to  be  gain- 
said ;  and  it  seems  established  that  strophanthus  acts  not  only  in  cases 
of  cardiac  disease  but  also  in  healthy  men  and  animals  as  a  powerful 
diuretic.  This  indicates  that  the  drug  has  a  direct  stimulating  influence 
upon  the  secreting  structure  of  the  kidneys,  a  conclusion  which  is  con- 
firmed by  the  renal  lesions  of  the  poisoning,  and  also  by  the  oncometric 
experiments  of  Phillips,  which  showed  that  strophanthus  does  not  cause 
vascular  congestion  of  the  kidneys. 

SUMMARY. — Strophanthus  is  primarily  a  muscle-poison,  whose 
influence,  -whatever  it  may  be  upon  the  nervous  system,  is  so  subordi- 
nate to  its  action  upon  the  voluntary  muscles  and  upon  the  circulation 
as  to  play  little  or  no  role  in  the  poisoning1.  In  concentrated  form,  how- 
ever, it  is  paralyzant  to  the  sensory  nerves  and  probably  to  other  por- 
tions of  the  nervous  system.  The  most  susceptible  portion  of  the  body 
to  its  influence  is  the  cardiac  muscle,  upon  which  and  also  probably 
upon  the  muscular  fibres  of  the  walls  of  the  vessels  it  acts  as  it  does 
upon  voluntary  muscles. 

THERAPEUTICS. — Strophanthus  is  used  in  practical  medicine  to  meet 
exactly  the  same  indications  as  those  for  which  digitalis  is  prescribed. 
It  is,  however,  less  powerful  and  less  certain  in  its  influence  for  good 
than  is  digitalis,  but  acts  more  promptly  and  more  fugaciously.  Its 
influence  usually  begins  in  half  an  hour  and  lasts  from  four  to  eight  hours. 
It  would  seem  to  be  indicated  especially  in  cases  of  acute  heart- failure,  but 
both  its  tincture  and  strophanthidin  are  locally  too  irritant  for  hypodermic 
use  except  in  cases  of  great  emergency.  When  actively  pushed,  it  prob- 
ably is  no  better  borne  by  the  stomach  than  is  digitalis  ;  but  experience  has 
shown  that  some  individuals  are  affected  unpleasantly  more  quickly  by 
strophanthus  than  they  are  by  digitalis,  whilst  in  others  the  opposite  is  the 
case.  In  chronic  heart  disease  strophanthus  stands  next  to  digitalis  in 
the  list  of  useful  heart  tonics  and  stimulants,  in  some  cases  acting  more 
favorably  than  digitalis  for  reasons  not  apparent,  in  others  extremely 
useful  in  combination  with  digitalis,  whilst  in  the  majority  of  instances  it 
is  chiefly  advantageous  as  a  remedy  to  take  the  place  of  digitalis  when  it 
is  from  time  to  time  suspended  for  the  purposes  of  resting  the  stomach  or 
of  preventing  cumulative  action.  Its  superiority  as  a  diuretic  makes  it  of 
especial  value  in  cases  of  pulmonic  oedema  or  of  general  cardiac  dropsy. 
When  given  in  overdose  it  produces  burning  in  the  oesophagus  and  the 
stomach,  with  gastric  distress  and  severe  vomiting. 

M.  Furbringer  u  reports  three  cases  in  which,  after  the  remedy  had  been  used  in 
a  large  quantity  and  for  a  long  time,  sudden  death  from  syncope  occurred.  It  may 
well  be  that  the  death  was  directly  caused  by  the  strophanthus,  but  it  is  more  prob- 


338  GENERAL    REMEDIES. 

ably  parallel  occurrence  to  what  often  happens  in  advanced  cardiac  disease  treated 
with  very  large  doses  of  digitalis. 

Zerner  and  Loaw 12  have  employed  strophanthus  with  alleged  success 
in  Basedow1  s  disease  and  in  Bright' s  disease,  and  they  consider  it  espe- 
cially useful  in  renal  affections  with  secondary  failure  of  the  heart,  a  con- 
dition in  which  we  have  seen  it  act  most  advantageously.  Rothziegel  and 
Koralzewski 1S  and  H.  Haas  "  commend  it  highly,  not  only  in  chronic  but 
also  in  acute  Bright' s  disease. 

The  U.  S.  Pharmacopoeia  recognizes  Strophanihin  (STROPHANTHI- 
NUM,  U.  S. )  and  officially  describes  it  as  a  glucoside  or  mixture  of 
glucosides  obtained  from  strophanthus;  it  also  assigns  to  it  the  dose  of 
one-two-hundredth  of  a  grain  (0.3  Mg. ).  Probably  in  many  cases  larger 
amounts  than  the  official  dose  are  necessary  to  obtain  the  desired  thera- 
peutic effect.  Rothziegel  and  Koralzewski  employ  from  one-three-hun- 
dredth to  one-two-hundredth  of  a  grain  (0.0002-0.00x33  Gm. ).  Stahr15 
affirms,  as  the  result  of  clinical  studies  with  Merck' s  crystalline  strophan- 
thin,  that  twenty  milligrammes,  or  three-tenths  of  a  grain,  may  be  given 
in  twenty-four  hours  without  producing  serious  results.  The  five  per 
cent,  tincture  of  strophanthus,  formerly  official,  was  used  in  doses  of  five 
to  ten  minims  (0.3-0.6  C.c. )  every  eight  hours,  but  the  present  tincture 
(TINCTURA  STROPHANTHI,  U.  S. )  is  of  ten  per  cent,  strength.  Dose, 
three  to  six  minims  (0.18-0.35  C.c.). 

CAFFEINA— CAFFEINE.     U,  S. 

Caffeine  occurs  in  long,  snow-white,  silky,  opaque,  odorless  crystals, 
sometimes  conjoined  into  feathery  crystals,  of  a  feeble  bitter  taste.  It 
has  a  neutral  reaction,  but  unites  with  acids  to  form  salts.  It  is  soluble, 
at  77°  F. ,  in  45.6  parts  of  water,  fifty-three  parts  of  alcohol,  three  hun- 
dred and  seventy-five  parts  of  ether,  or  seven  parts  of  chloroform.  It  was 
first  discovered  in  coffee  by  Runge,1  in  1820.  In  1827  Oudry  discovered 
a  principle  in  tea  which  he  called  theine,  which  in  1838  was  proved  by 
Mulder  and  C.  Jobst  to  be  identical  with  caffeine.*  Caffeine  is  somewhat 

*  Caffeine  has  been  found  in  the  leaves  of  the  American  Ilex  cassine,  which  was 
quite  largely  used  under  the  name  Yaupon  by  the  North  American  Indians,  and  is  still 
employed  in  making  black  drink  or  holly  tea  in  the  coast  districts  of  North  Carolina  and 
Virginia.  Caffeine  is  also  the  active  principle  of  the  kola  nuts  which  are  yielded  by  Ster- 
culia  acuminata  of  the  Soudan,  and  are  asserted  to  contain  0.7  to  2.5  per  cent,  of  the  al- 
kaloid, besides  a  peculiar  tannic  acid.  It  has  been  claimed  by  several  observers  that  the 
action  of  the  kola  nut  differs  from  that  of  caffeine,  but  the  elaborate  studies  of  A.  Mosso 
seem  to  prove  that  no  such  difference  exists.  As  much  as  one  hundred  and  fifty  grains 
of  the  kola  nut  have  been  given  in  the  course  of  the  day  with  alleged  good  results  in 
cardiac  weakness. 

Under  the  name  of  Mate,  or  Paraguay  tea,  the  leaves  of  the  Ilex  Paraguaiensis  are 
used  in  South  America  to  the  extent  of  many  thousands  of  tons  annually.  They  are  said 
to  contain  from  0.5  to  1.8  per  cent,  of  caffeine,  besides  much  caffeotannic  acid.  Mate  is 
sold  in  two  forms  :  mate  in  leaf  is  prepared  as  ordinary  tea  is,  and  taken  with  sugar  and 
milk  to  taste  ;  mate  in  powder  is  prepared  by  pouring  upon  the  powdered  mate  boiling 
water,  and  the  infusion  is  sucked  up  through  a  tube,  the  bulbous  end  of  which  is  fur- 


CARDIAC   STIMULANTS.  339 

widely  disseminated  through  the  vegetable  kingdom,  but  is  commercially 
chiefly  obtained  from  damaged,  or  originally  very  inferior,  tea. 

CAFFEINA  CITRATA,  U.  S.*  (Citrated  Caffeine),  often  incorrectly 
termed  citrate  of  caffeine,  is  a  mixture  of  equal  parts  of  caffeine  and  citric 
acid.  It  is  a  white  bitter  powder,  soluble  in  about  four  parts  of  hot 
water  and  twenty-five  parts  of  cold  water. 

CAFFEINA  CITRATA  EFFERVESCENS,  U.  S. ,  contains  four  per  cent,  of 
citrated  caffeine  with  sodium  bicarbonate  and  tartaric  and  citric  acids  to 
produce  the  effervescence. 

Local  Action. — Absorption  and  Elimination. — Caffeine  is  not  irritant, 
and  for  practical  purposes  may  be  considered  to  have  no  local  action,  ex- 
cept it  be  upon  the  sensory  nerves.  It  'is  absorbed  rapidly  ;  elimin- 
ated chiefly  through  the  kidneys,  when  in  large  amount  in  part  un- 
changed, when  in  small  quantity  entirely  altered  (Richard  Schneider,2 
also  E.  Rosts).  According  to  M.  Albanese,4  at  least  a  part  of  the  caf- 
feine (trimethylxanthine)  appears  in  the  urine  as  dimethylxanthine,  mon- 
omethylxanthine,  or  even  xanthine. 

GUARANA,  U.  S.,  is  a  dried  paste,  prepared  from  the  seeds  of  Paullinia  ciipana, 
a  Brazilian  plant.  It  occurs  in  reddish-brown  almost  sausage-like  masses,  rugose 
on  the  surface,  very  hard,  with  an  irregular  fracture  and  a  marbled  appearance 
when  broken.  Its  taste  is  astringent  and  bitterish  ;  its  odor  somewhat  resembles 
that  of  chocolate.  The  alkaloid  guaranine,  discovered  in  it  by  Martius,  has  been 
shown  to  be  identical  with  caffeine.  The  Pharmacopoeia  requires  that  guarana 
shall  contain  3.5  per  cent,  of  alkaloids.  It  has  also  in  it  free  tannic  acid  and  a 
fixed  oil. 

Guarana  is  prepared  to  be  used  as  a  caffeinic  drink  by  the  Brazilian  aborigines, 
but  has  been  largely  employed  in  the  treatment  of  migraine;  it  is  not,  however, 
in  any  way  superior  to  pure  caffeine.  Its  astringent  and  stimulant  properties  make 
it  useful  in  atonic  chronic  diarrhoea.  Dose  of  the  powder,  one  to  two  drachms 
(4  to  8  Gm. )  ;  of  the  FLUIDEXTRACTUM  GUARANA,  U.  S.,  one  to  two  fluidrachms 
(4to8C.c.) 

General  Action. — The  peculiar  wakefulness,  the  increased  mental 
activity,  and  the  nervous  restlessness  which  are  induced  by  strong  coffee 
are  familiar  phenomena  to  almost  every  one.  They  are  without  doubt 
largely,  if  not  altogether,  due  to  the  caffeine  contained  in  the  beverage,  f 

nished  with  a  fine  sieve,  or  the  powder  is  thrown  into  boiling  water,  and  when  the  mixture 
recommences  boiling,  cold  water  is  poured  into  it ;  this  precipitates  the  powder,  and  the 
infusion  is  taken  clear. 

*  The  belief  of  Thomas  J.  Mays,  based  on  physiological  experimentation,  that  caf- 
feine, guaranine,  and  theine  act  dissimilarly  upon  the  normal  organization  is  not  in 
accord  with  previous  or  with  later  studies.  For  discussion  and  literature  see  p.  317, 
Eleventh  Edition  of  this  work. 

t  The  beverage  coffee  differs  so  in  its  effects  from  tea,  and  it  is  said  also  from  the 
drink  made  from  green  coffee,  as  to  lead  to  the  conclusion  that  its  action  depends,  at  least 
in  part,  on  some  substance  or  substances  formed  during  the  process  of  roasting.  Since 
the  publication  of  J.  Lehmann  in  1853,  stating  that  the  empyreumatic  oil  of  coffee  is  an 
active  substance,  various  investigations  have  been  made  upon  this  so-called  caffeone,  with 
reports  whose  contradictory  character  is  probably  largely  dependent  upon  different  sub- 
stances having  been  used  by  the  various  investigators.  For  a  general  epitome  of  the 
earlier  literature  of  the  subject  the  reader  is  referred  to  the  papers  cited  below. 


340  GENERAL  REMEDIES. 

By  doses  of  four  or  five  grains  of  the  alkaloid  a  somewhat  similar  state 
of  body  and  mind  may  be  induced.  Lehmann  found  that  eight  grains  of 
caffeine  produced  increased  frequency  of  the  pulse,  very  frequent  urina- 
tion, tremulousness,  excited  mental  action,  passing  into  a  form  of  delirium, 
with  confusion  of  thought,  visions,  and  finally  a  deep  sleep.  About  two 
hours  after  taking  twelve  grains,  Pratt  was  seized  with  intense  physical 
restlessness,  conjoined  with  a  very  uneasy  condition  of  the  mind  ;  very 
marked  general  muscular  tremulousness  soon  followed,  and  the  mental 
anxiety  increased.  After  this  state  passed  off,  there  was  obstinate  sleep- 
lessness, with  active  and  persistent  thinking,  and  frequent  urination. 

According  to  various  observers,  the  chief  symptoms  induced  by  poisonous  doses 
of  caffeine  in  the  frog  are  muscular  quietness  and  weakness,  with  disturbance  of  res- 
piration, succeeded  by  a  stage  of  violent  tetanic  convulsions,  ending  in  general 
paralysis  and  asphyxia,  the  heart  beating  after  the  cessation  of  respiration,  although 
evidently  much  affected.* 

In  1880,  Bernheimer  (Monatsch.f.  Chemie,  1.)  obtained  from  roast  coffee  an  empyreu- 
matic  volatile  oil  to  which  he  gave  the  name  of  caffeol,  and  which  he  believed  to  be  a 
methyl  derivative  of  saligenin ;  besides  it  and  caffeine  Bernheimer  obtained  from  the 
roasted  coffee  hydrochinon,  methylamin,  pyrrol,  and  aceton.  H.  Jaeckle  (Zeitscli.  f. 
Unters.  d.  Nahrungs  u.  Gemiss.,  1898)  failed  to  get  "caffeol,"  but  in  a  recent  investiga- 
tion Erdmann  (Archiv  f.  Exper.  Path.  u.  Pharm.,  1902,  Bd.  48)  secured  it  as  a  brown, 
oily  substance  with  a  strong  odor  of  coffee  and  an  acid  reaction,  having  a  specific  gravity 
of  1.0844.  From  this  oil  Erdmann  separated  valerianic  acid,  furfur-alcohol,  a  peculiar 
nitrogenous  substance  having  strongly  the  aroma  of  coffee,  and  various  phenols ;  the  chief 
constituent  \\SLsfurfur-alcohol,  there  being  at  least  fifty  per  cent,  of  it. 

The  substance  used  by  Hare  and  Marshall  (Med.  News,  Phila.,  lii.)  and  by  E.  T. 
Reichert  (Ibid.,  1890.  Ivi.)  was  obtained  by  extraction  from  roast  coffee  with  petroleum 
ether.  The  first  observers  believed  they  proved  this  empyreumatic  oil  to  be  active,  but 
Reichert  found  it  was  without  physiological  influence,  excepting  in  so  far  that  when  given 
intravenously  it  mechanically  interfered  with  the  circulation.  In  Binz's  experiments 
(C.  I.  M.,  1900,  xxi.)  the  distillate  of  coffee  caused  feeble  excitement,  with  restlessness 
and  increase  in  the  rate  and  depth  of  respiration, — a  result  in  accord  with  those  obtained 
by  Archangeleski  (A.  I.  P.  T.,  1900,  vii.).  According  to  the  experiments  of  Erdmann, 
furfur-alcohol  when  given  to  rabbits  in  doses  of  between  0.5  and  0.6  grammes  per  kilo- 
gram produces  a  short  primary  excitement  followed  by  salivation,  diarrhoea,  respiratory 
depression,  progressive  failure  of  the  bodily  temperature,  collapse,  ending  in  death  from 
respiratory  failure.  In  man,  doses  of  0.6  to  i  gramme  of  furfur-alcohol  increased  the  res- 
piratory activity  without  producing  other  symptoms.  Archangeleski  produced  in  man 
with  the  coffee  distillate  some  general  stimulation,  and  is  probably  correct  in  his  conclu- 
sion that  the  stimulation  caused  by  coffee  is  due  to  some  extent  to  the  volatile  substances 
contained  in  it. 

*  See  Albers  (Deutsche  Klinik,  1853,  37°).  Falck  and  Stuhlmann  ( I  'irchow's  Archil', 
xi.  334),  Mitscherlich  (Der  Cacao  und  die  Chocolade,  Berlin,  1859),  1.  Hoppe  (IJ1  Echo 
Med.,  1858),  Brill  (Inaug.  Diss.,  Marburg,  1861),  Oscar  Johannsen  (Inaug.  Diss.,  Dorpat, 
1869),  and  others.  The  minimum  fatal  dose  is  stated  by  Leven  (Arch,  dc  Physiol.,  1858) 
to  be  .015  grain  in  a  frog  of  moderate  size. 

Johannsen  denies  the  existence  of  true  convulsions  in  the  frog,  asserting  that  there  is 
only  a  rigidity  due  to  an  effect  upon  the  muscles. 

Buchheim  and  Eisenmenger  (quoted  by  Schmiedeberg)  corroborate  the  musculai 
changes  noted  by  Johannsen,  but  insist  that  there  are  also  true  nervous  convulsions.  O. 
Schmiedeberg  (Atchiv  fiir  Exper.  Pathol.  und  Pharm.,  ii.)  believes  that  he  has  recon- 
ciled these  differences  of  observation  by  finding  that  the  alkaloid  acts  much  more  power- 
fully upon  the  muscles  of  Rana  temporaria  than  upon  those  of  Rana  esculenta  ;  so  that  a 
dose  of  caffeine  which  causes  intense  general  muscular  stiffness  in  the  former  produces 
in  the  latter  only  true  convulsions,  the  convulsions  in  R.  temporaria  being  prevented 
or  masked  by  the  disorder  of  the  muscles.  More  recent  researches  (E.  Leblond,  La 


CARDIAC   STIMULANTS.  34i 

In  birds  poisoned  with  caffeine  the  symptoms  (Brill5)  are  irregular  movements, 
apparently  to  some  extent  due  to  cerebral  disturbance,  increased  rapidity  and  irreg- 
ularity of  respiration,  spasmodic  tremblings,  and  tetanic  and  clonic  convulsions,  with 
paralytic  phenomena.  In  mammals  the  results  of  the  toxaemia,  as  noted  by  various 
observers,  are  restlessness,  hurried  respiration,  at  first  a  slight  lowering  and  after- 
wards a  decided  elevation  of  temperature,  muscular  weakness,  tetanic  and  clonic 
convulsions,  increasing  general  paresis,  and  finally  death,  apparently  from  paralytic 
arrest  of  respiration.* 

Cerebrum. — There  is  no  evidence  that  caffeine  exerts  a  very  marked 
influence  upon  the  cerebrum  of  the  frog,  or  even  of  some  of  the  lower 
mammals,  unless  the  convulsions  induced  by  it  are  believed  to  be  partly 
the  result  of  some  such  action.  In  certain  of  the  higher  animals,  such  as 
the  cat,  it  often  produces  a  condition  of  almost  frantic  cerebral  excite- 
ment. In  man  the  increase  of  brain-power  produced  by  coffee,  tea, 
guarana,  and  other  drugs  containing  caffeine  and  the  allied  alkaloids  is 
undoubtedly  real,  and  we  must  conclude  that  caffeine  is  a  powerful 
stimulant  to  the  cerebral  cortex.  It  appears  to  us  to  be  our  most  certain 
and  effective  stimulant  of  the  nerve-centres  connected  with  the  intel- 
lectual functions.  Those  centres  whose  function  is  consciousness  are 
greatly  stimulated,  and  wakefulness  results  ;  while  again,  in  contrast  with 
opium,  caffeine  increases  the  activity  and  power  of  the  reasoning  facul- 
ties at  least  as  much  as  it  does  that  of  the  imagination.  Coffee  prepares 
for  the  active  work,  both  mental  and  physical,  while  opium  leads  its 
votaries  to  the  dream-land  of  poets. 

Spinal  Cord. — There  has  been  much  discussion  as  to  the  method  in 
which  caffeine  produces  convulsions  in  the  frog,  but  it  seems  to  be  estab- 
lished that  they  are,  at  least  in  part,  of  spinal  origin.  They  are  not  pre- 
vented by  section  of  the  cord  high  up  (Pratt  and  Leblond),  therefore 
they  are  not  cerebral  :  they  are  prevented  by  destruction  of  the  spinal 
cord  (LevenB),  and  would  appear,  therefore,  to  be  spinal. 

The  difficulty  of  interpretation  of  the  phenomena  has  arisen  from  the  fact  that 
the  muscular  action  of  the  alkaloid  in  a  measure  masks  its  influence  upon  the 
spinal  cord,  there  being  both  muscular  stiffness  of  purely  muscular  origin  and  con- 
vulsions of  spinal  origin.  This  was  clearly  demonstrated  by  Pratt,  who  found  that 
though  destruction  of  the  lower  portion  of  the  spinal  cord  prevented  the  convul- 
sions in  the  hind  legs  of  the  frog,  it  did  not  interfere  with  the  development  of  the 
contractures.  Further,  Pratt  included  all  the  tissues  of  a  frog,  except  the  spine,  in 
a  tight  ligature  just  above  the  bifurcation  of  the  aorta,  and  administered  caffeine, 
when  the  anterior  legs  became  very  stiff,  and  had  also  occasional  severe  convul- 
sions, in  which  the  hind  legs  participated,  although  between  the  paroxysms  they 
were  perfectly  relaxed. 

Caffeine,  Paris,  1883 ;  W.  Filehne,  Arch.  f.  Anal,  und  Physiol.,  1886)  indicate,  however, 
that  the  differences  depend  to  some  extent  upon  the  size  of  the  dose,  but  in  still  greatei 
degree  upon  variations  in  the  sensitiveness  of  individual  frogs ;  thus,  Kobert  (Arch.f. 
Exper.  Path.  u.  Pharm.,  xv. )  found  that  frogs  of  the  same  species  are  very  much  more 
susceptible  in  the  spring  than  in  the  autumn.  The  rigidity  and  paralysis  are  muscular. 
*  In  an  elaborate  series  of  experiments,  Bennett  (British  Medical  Journal,  1874)  found 
that  the  fatal  minimum  dose  of  the  poison  for  the  cat  and  the  rabbit  was  a  little  over  a 
grain  for  the  pound,  five  and  a  half  grains  being  required  for  a  five-pound  animal. 


342  GENERAL    REMEDIES. 

The  conclusion  seems  established  that  in  the  frog  caffeine  acts  as  a 
motor  spinal  stimulant  and  also  as  a  muscle-poison.  *  The  physical  rest- 
lessness and  tremulousness  produced  in  man  by  excessive  doses  of  coffee 
and  tea,  and  the  convulsions  of  caffeine-poisoning,  are  probably  both  spinal 
and  cerebral,  though  our  knowledge  of  this  matter  is  incomplete,  f 

Nerves. — The  motor  nerves  appear  not  to  be  affected,  but  the  sen- 
sory nerves  are  apparently  slightly  affected. 

Alexander  Bennett1  has  found  that  after  death  from  theine  the  motor  nerves  re- 
tain their  normal  susceptibility,  and  Pratt  surrounded  one  crural  nerve  of  a  frog  with 
a  paste  "of  theine  and  water,"  and  irritated  the  spinal  cord,  when  both  legs  re- 
sponded with  uniform  alacrity.  Bennett  also  tied  the  crural  artery  of  a  frog,  poi- 
soned it  with  the  alkaloid,  and  found  that  irritation  of  the  cord  produced  equally 
active  contractions  in  the  two  legs.  The  chief  evidence  as  to  the  sensory  nerves  is 
furnished  by  Pratt,  who  found  that  when  the  left  sciatic  nerve  of  a  frog  was  sur- 
rounded by  a  paste  of  theine  and  water,  after  ten  minutes  irritation  of  the  right  foot 
produced  reflex  movements,  while  irritation  of  the  left  foot  failed  to  elicit  any  re- 
sponse. Leblond8  has  noted  marked  hyperaesthesia  in  the  frog,  and  Rumpf9 
affirms  that  increased  sensibility  of  the  skin  can  be  demonstrated  in  man. 

Muscle. — The  action  of  caffeine  upon  the  muscle  is  readily  demon- 
strated by  throwing  the  isolated  gastrocnemius  of  the  frog  into  a  one 
per  cent,  or  even  a  weaker  solution  ;  in  from  two  to  three  minutes  the 
muscle  becomes  markedly  contracted,  swollen,  round,  stiff,  and  unable 
to  respond  to  the  galvanic  -current.  That  it  is  the  muscle-fibre  which  is 
affected  is  shown  by  the  experiments  of  Pratt,  who  found  that  when  an 
isolated  muscle  was  soaked  in  a  solution  of  curare  until  the  nerves  were 
killed,  and  then  thrown  into  a  solution  of  caffeine,  the  usual  rigidity  was 
developed.  The  elaborate  studies  of  Leblond  appear  to  prove  that  there 
are  two  stages  (as  in  veratrine-poisoning)  in  the  action  of  caffeine  upon  the 
frog  muscle, — a  primary  stage,  with  exaggerated  muscular  excitability  and 
a  tendency  to  prolonged  tetanic  contractions  after  momentary  stimulation, 
and  a  final  stage  of  rigidity  and  lost  excitability.  J  W.  Sobieranski 10 
believes  that  his  ergographic  experiments  prove  that  in  fatigue  caffeine 
not  only  stimulates  the  nervous  system  and  thereby  increases  working 
power,  but  also  acts  directly  upon  the  muscle. 

According  to  the  researches  of  Paschkis  and  Pal,11  it  would  appear  to 
be  the  xanthine  which  influences  the  muscle-fibre,  since  these  investigators 
found  that  caffeine  (trimethylxanthine),  theobromine  (dimethylxanthine), 

*  Alexander  Bennett  has  brought  forward  the  theory  (loc.  cit,  and  British  Medical  Jour- 
nal, 1874)  that  caffeine  paralyzes  the  posterior  columns  of  the  cord  without  affecting  the 
anterior  columns ;  but  his  evidence  appears  to  us  insufficient  to  prove  his  conclusions. 
He  grounds  his  belief  chiefly  on  finding  that  in  poisoned  frogs  and  rabbits  galvanization 
of  the  posterior  columns  of  the  exposed  cord  produced  either  no  muscular  contractions 
or  only  such  as  were  very  much  more  feeble  than  those  provoked  by  galvanization  of  the 
anterior  columns. 

t  Uspensky  (Reicherfs  Archiv,  1868,  526)  has  found  that  forced  artificial  respiration 
in  great  measure  suspends  the  convulsions. 

J  Johannsen  states  that  when  a  muscle  under  the  microscope  is  touched  with  caffeine, 
its  fibres  can  be  seen  to  contract  half  their  length. 


CARDIAC   STIMULANTS.  343 

and  xanthine  shared  the  activity  ;  caffeine  being  the  strongest,  xanthine 
the  weakest. 

Circulation.  — Caffeine  has  a  direct  influence  upon  the  heart,  although 
that  viscus  continues  to  beat  in  animals  poisoned  by  the  drug  after  the 
cessation  of  respiration. 

According  to  Voit  (quoted  by  Brill),  in  the  frog  the  rapidity  of  the  cardiac  pul- 
sation is  at  first  increased,  but  the  pulsations  become  slower  and  slower,  and  are 
accompanied  by  irregularity  of  rhythm,  the  heart  finally  ceasing  to  act,  but  still 
responding  to  stimuli  at  a  time  when  the  voluntary  muscles  are  absolutely  dead. 
Falk  and  Stuhlmann,12  and  Johannsen  "  observed  that  caffeine  first  increases  and 
then  lessens  the  frequency  of  the  cardiac  pulsations  in  the  frog.  According  to 
Johannsen,  the  lessening  of  the  frequency  comes  on  the  more  quickly  and  the  more 
powerfully  as  the  size  of  the  dose  is  increased.  After  a  time  the  heart  begins  to 
beat  irregularly,  with  short  intermissions,  which,  as  time  goes  on,  grow  longer  and 
longer,  till  at  last  movement  ceases.  Johannsen  found  that  the  action  upon  the 
cut-out  frog's  heart  was  the  same  upon  the  viscus  in  situ ;  Leblond  confirms  this, 
and  states  that  the  heart  is  finally  arrested  in  systole  ;  so  also  does  Thomas  J.  Mays.1* 
Aubert  and  Haase 15  find  that  the  action  of  the  alkaloid  upon  the  pulsations  of  the 
frog's  heart  varies  greatly  ;  and  indeed  the  individual  experiments  of  the  authors 
previously  quoted  show  such  variation.  This  is  confirmed  by  the  research  of  Rios- 
chiro  Maki.16  This  investigator  experimented  upon  the  cut-out  frog's  heart  with 
the  Williams  apparatus,  and  found  that  the  pulse  was  variously  affected.  In  most 
of  his  experiments  the  arterial  pressure — i.e.,  the  heart's  work — was  markedly 
lessened,  but  in  a  few  cases  it  was  distinctly  increased. 

The  conclusion  that  caffeine  exerts  a  double  influence  upon  the  frog's 
heart,  in  small  doses  stimulating  it  and  increasing  its  work,  and  in 
larger  doses  paralyzing  it,  seems  to  be  confirmed  by  Paul  Faval,"  who 
finds  that  in  a  proportion  of  ten  centigrammes  to  one  hundred  and  fifty 
grammes  of  artificial  blood  the  alkaloid  reinforces  the  isolated  frog's 
heart,  giving  its  contractions  more  amplitude  and  more  energy,  but  that 
stronger  doses  depress  the  heart,  and  finally  arrest  it  in  diastole  ;  and 
by  H.  C.  Beyer,18  who  has  reached  similar  conclusions  with  the  terra- 
pin's heart. 

The  results  obtained  by  various  experimenters  as  to  the  influence  of 
caffeine  on  the  circulation  in  mammals  are  in  their  general  appearance 
contradictory,  but  are,  however,  we  believe,  reconcilable. 

In  attempting  such  reconciliation  it  seems  better  to  discuss  separately  the 
effects  of  the  drug  upon  arterial  pressure  and  pulse-rate.  In  the  Aubert  and  Haase 
experiments,  caffeine  usually  produced  pronounced  fall  of  the  arterial  pressure, 
although  in  one  experiment  there  was  a  distinct  rise.  It  is  to  be  noted  that  the 
research  was  made  with  enormous  doses  of  caffeine,  and  usually  upon  dogs  under 
the  influence  of  narcotics.  In  two  experiments  upon  alcoholized  dogs,  Binz  w  ob- 
tained a  pronounced  rise  of  the  arterial  pressure  ;  while  Maki,  experimenting  upon 
animals  under  the  influence  of  atropine  or  chloral,  obtained  after  large  doses  a  dis- 
tinct fall  of  the  arterial  pressure,  which  in  a  few  cases  was  preceded  by  a  rise.  It 
is  evident  that  the  method  of  research  employed  in  these  experiments  makes  it 
impossible  to  draw  any  very  positive  conclusions.  In  normal  animals,  Leven  found 
in  the  first  stages  of  caffeine-poisoning  a  distinct  increase  of  the  arterial  pressure, 
and  in  the  elaborate  experiments  of  Reichert20  it  was  noted  that  in  the  normal  dog 


344  GENERAL  REMEDIES. 

caffeine  injected  into  the  jugular  vein,  in  moderate  amount,  caused  a  primary  fall 
of  pressure  (evidently  due  to  an  overwhelming  effect  of  the  concentrated  alkaloid 
upon  the  heart),  followed  by  a  rise  above  the  norm,  followed  in  turn,  if  the  dose 
had  been  large  enough,  by  a  marked  fall  of  pressure.  Very  large  doses  of  caffeine 
produced  a  persistent  fall  of  pressure,  ending  in  final  diastolic  arrest  of  the  heart. 
In  none  of  Reichert's  experiments  was  the  rise  of  arterial  pressure  very  great,  but, 
except  after  heavily  toxic  doses,  it  occurred  almost  invariably.  Leven  asserts  that 
after  he  had  divided  the  pneumogastrics  and  sympathetics  and  isolated  the  heart 
from  all  the  nerve-centres,  caffeine  still  increased  the  arterial  pressure  ;  while 
Reichert  states  that  not  only  is  the  increase  of  the  pressure  seen  when  the  animal  is 
motionless  with  curare,  but  also  after  destruction  of  the  vaso-motor  centres  in  the 
medulla  oblongata.  Loewi 41  in  oncometrical  experiments  on  the  intestines  failed 
to  obtain  any  evidences  of  the  contraction  of  these  vessels  with  caffeine  and  believes 
that  the  rise  of  blood-pressure  is  purely  cardiac.  Experimenting  on  the  isolated 
mammal  heart,  Bock40  found  that  though  there  was  a  continual  increase  in  the  rate 
of  the  pulse  in  the  majority  of  the  experiments  the  pressure  exerted  by  the  left 
heart  was  lowered,  although  in  a  considerable  minority  it  was  first  elevated,  espe- 
cially when  a  small  dose  of  the  caffeine  had  been  given.  Bock  concludes  from 
these  experiments  that  the  elasticity  of  the  heart-muscle  is  diminished  by  caffeine, 
and  that  the  elevation  of  the  arterial  pressure  naturally  produced  by  caffeine  in  the 
normal  animal  is  due  to  contraction  of  the  blood-vessels.  The  method  of  experi- 
mentation seems  to  us  very  uncertain,  and  the  result  is  in  direct  discord  with  other 
experiments  already  cited. 

The  total  evidence  seems  to  us  conclusively  to  show  that  caffeine  in- 
creases the  arterial  pressure  independently  of  the  vaso-motor  centres. 
Reichert  believes  the  rise  to  be  due  to  an  action  on  the  muscle-fibre  in 
the  walls  of  the  blood-vessels.  It  does  not,  however,  seem  to  us  proba- 
ble that  the  vascular  action  is  the  sole  cause  of  the  rise  of  the  arterial 
pressure.  The  evidence  of  the  experiments  upon  the  frog's  heart  is  so 
direct  that  the  probabilities  are  that  small  doses  of  caffeine  act  directly 
upon  the  heart  as  a  stimulant,  and  that  therefore  although  in  the  ad- 
vanced stages  of  caffeine-poisoning  both  the  heart  and  the  vascular  system 
are  without  doubt  depressed,  in  the  earlier  stages  of  the  poisoning,  or  after 
small  doses  of  caffeine,  both  the  heart  and  the  vascular  system  are  stimu- 
lated by  a  direct  action  upon  the  muscle-fibres,  giving  rise  to  an  increase 
of  the  arterial  pressure. 

In  the  advanced  stages  of  caffeine-poisoning  both  tJie  heart  and  the 
vaso-motor  system  are  without  doubt  depressed,  so  that  the  cause  of  the 
fall  of  pressure  is  duplex. 

In  regard  to  the  pulse,  Aubert  notes  as  a  constant  effect  an  increase  of 
the  pulse-rate,  and  this  appears  to  be  the  most  frequent  result  produced 
by  caffeine  ;  but  it  has  been  shown  by  Reichert  that  under  certain  cir- 
cumstances there  is  a  slowing  of  the  pulse. 

Leven  asserts  that  the  increase  of  the  pulse-rate  is  to  be  seen  after  isolation  of 
the  heart  from  the  nervous  centres,  and  is,  therefore,  due  to  an  action  upon  the 
heart  itself,  a  conclusion  which  is  in  accord  with  the  general  results  of  observations 
upon  the  isolated  frog's  heart,  and  is  confirmed  by  Reichert,  who  believes  that 
there  are  paralyses  of  the  cardio-inhibitory  centres,  both  in  the  medulla  oblongata 
and  the  heart.  The  slowing  of  the  pulse  occasionally  seen  in  the  first  stages  of  the 


CARDIAC   STIMULANTS.  345 

poison  Reichert  attributes,  with  probable  correctness,  to  a  primary  stimulation  of 
these  cardio-inhibitory  centres  ;  the  alteration  of  the  pulse  which  sometimes  occurs 
in  advanced  poisoning  he  believes  to  be  due  to  a  direct  action  of  the  drug  upon  the 
heart.  Bock  believes  that  the  frequency  of  the  pulse  usually  produced  by  caffeine 
is  the  outcome  of  powerful  stimulation  of  the  accelerator  cardiac  apparatus,  and 
that  the  inhibitory  apparatus  is  not  depressed,  basing  the  latter  belief  on  the  fact 
that  he  has  observed  that  section  of  the  vagi  in  the  poisoned  animal  still  further  in- 
creases the  rapidity  of  the  pulse  whose  rate  is  already  much  above  the  normal. 

Diuretic  Action. — In  poisoning  by  caffeine  great  increase  in  the  secre- 
tion of  urine  is  a  common  symptom,  and  the  statement  of  Gubler 21  that 
the  alkaloid  is  one  of  our  most  powerful  and  certain  diuretics,  has  re- 
ceived abundant  confirmation.  The  effect  of  the  drug  upon  healthy  men 
would  indicate  that  in  dropsies  it  does  not  act  simply  by  regulating  the 
circulation  of  the  kidney,  but  has  also  a  distinct  effect  upon  the  renal 
organ  itself. 

That  caffeine  acts  directly  upon  the  kidneys  was  proved  by  W.  von  Schroder 
and  by  A.  Langgaard,22  who  separately  found  that  when  a  canula  was  inserted  into 
the  ureters  in  an  animal  whose  vaso-motor  system  was  completely  paralyzed  by 
chloral,  injections  of  caffeine  into  the  circulation  caused  a  very  great  increase  in  the 
urinary  secretion.  Langgaard  found  that  usually  before  the  great  increase  of  diuresis 
the  urinary  secretion  was  arrested  for  several  minutes.  This  is  in  exact  accord 
with  the  experiments  of  C.  D.  T.  Phillips23  made  with  Roy's  oncometer.  It  was 
found  that  immediately  after  the  injection  of  a  small  dose  of  caffeine,  when  the 
blood-pressure  was  either  slightly  depressed,  elevated,  or  unaffected,  the  kidney 
underwent  a  very  distinct  contraction  of  its  volume,  which  lasted  for  two  or  even 
three  minutes  and  was  accompanied  by  great  lessening  or  arrest  of  the  urinary 
secretion.  After  the  contraction,  the  kidney  rapidly  expanded  beyond  its  original 
bulk,  and  at  the  same  time  the  urinary  secretion  became  excessive.  Loewi  found 
that  caffeine  is  capable  of  dilating  the  blood-vessels  after  division  of  the  renal  nerves 
and  believes  that  the  increased  activity  of  the  kidneys  depends  upon  vascular  dila- 
tation. These  facts  do  not  prove,  however,  that  the  diuresis  is  caused  by  the  in- 
creased flow  of  blood  to  the  kidneys.  It  is  more  probable  that  the  dilatation  of  the 
vessels  is  the  result,  rather  than  the  cause,  of  the  increased  secretion.  Because  the 
secretion  from  the  uninjured  kidney  was  increased  much  more  than  from  the  kid- 
ney whose  nerves  were  destroyed,  Schroder  believes  that  the  drug  increases  diuresis 
by  acting  both  upon  the  nerve-centres  and  upon  the  secreting  structure  of  the  kid- 
ney. To  our  thinking,  however,  the  direct  injury  to  the  secreting  apparatus  of  the 
kidney  by  division  of  the  renal  nerves  is  sufficient  to  account  for  the  difference 
between  the  influence  of  the  alkaloid  upon  the  normal  and  the  operated-upon  kid- 
ney, without  necessitating  the  theory  of  a  twofold  action.  Schroder  found  that 
there  was  an  increase  not  only  of  the  liquid,  but  also  of  the  solids  of  the  urine. 
Anten  ^  believes  that  caffeine  increases  an  inhibitory  influence  of  the  pneumogastric 
nerve  on  the  kidney,  thereby  interfering  with  its  non-excretive  influence,  a  theory 
which  seems  to  us  extremely  doubtful. 

Temperature. — We  know  of  no  recorded  temperature-curves  of  caf- 
feine-poisoning in  man.  It  is  probable,  however,  that  the  effect  of  the 
alkaloid  is  precisely  what  it  is  in  other  mammals.  Binz  states  that  in  ani- 
mals minute  doses  have  no  effect  upon  the  bodily  temperature  ;  doses  just 
enough  to  produce  slight  toxic  symptoms  cause  a  rise  of  0.6°  C.  ;  ex- 
cessive doses  cause  an  elevation  of  i°  to  1.5°  C. ,  the  maximum  being 


346  GENERAL  REMEDIES. 

reached  in  one  to  two  hours  ;  doses  which  rapidly  kill  have  very  little 
effect  upon  the  temperature. 

General  Nutrition. — The  enormous  use  made  by  mankind  of  sub- 
stances containing  caffeine  indicates  that  in  some  way  it  is  directly  of 
service  in  the  wear  and  tear  of  daily  life.  It  is  not  probable  that  any  of 
the  caffeine  is  assimilated,  but  it  is  thought  by  some  authorities  to  check 
very  greatly  the  elimination  of  nitrogen,  or,  in  other  words,  to  lessen  the 
waste  of  tissue. 

This  subject  was  laboriously  investigated  by  Julius  Lehmann  in  1853,  and  by  F. 
W.  Bocker 2*  in  1854,  and  earlier.  Lehmann  found  that  the  exhibition  of  six  grains  of 
caffeine  daily,  the  regulated  diet  being  uniform,  diminished  the  elimination  of  urea 
from  twelve  to  twenty  per  cent.  Upon  experimenting  with  the  empyreumatic  oil 
of  coffee  he  found  that  it  lessened  even  to  a  proportionately  greater  extent  the  elim- 
ination of  urea,  and  also  acted  very  powerfully  in  producing  sleeplessness,  so  that 
the  favorite  beverage  is  by  no  means  dependent  upon  its  contained  caffeine  for  all  of 
its  activity.  Bocker25  published  his  first  researches  on  coffee  in  1849,  but  we  have 
never  seen  any  abstract  of  the  article,  other  than  the  statement  that  he  found  that 
the  drug  causes  diminished  elimination  of  urea.  His  investigation  of  the  effect  of 
tea  was  most  elaborate  and  laborious.  He  analyzed  the  faeces,  the  urine,  and 
the  products  of  respiration,  and  found,  a  similar  diet  being  maintained,  that  tea  did 
not  affect  sensibly  the  elimination  of  carbonic  acid  from  the  lungs,  but  did  very 
decidedly  diminish  the  excretion  of  urea,  and  also  of  nitrogenous  matters  in  the 
faeces.  He  then  tried  abstaining  from  food  for  periods  of  thirty-six  hours,  with  and 
without  the  use  of  tea,  with  results  perfectly  in  accord  with  those  just  stated.  The 
results  obtained  by  other  experimenters  are,  however,  singularly  discordant. 
Henri  Hoppe26  found  that  in  the  dog  coffee  diminishes  very  slightly  the  urea- 
elimination,  but  greatly  increases  the  output  of  carbonic  acid.  In  regard  to  urea, 
Rabuteau  and  his  pupil  Eurastratiade,  working  with  coffee  upon  men  and  dogs,  ob- 
tained results  similar  to  those  of  Bocker,27  as  did  also  Hammond  in  this  country. 
On  the  other  hand,  C.  G.  Lehmann,28  Voit,29  and  Roux  ™  found  that  caffeine  or  coffee 
sensibly  increases  the  elimination  of  urea,  or,  in  those  accustomed  to  the  daily  use 
of  coffee,  has  no  influence.  In  a  long  series  of  experiments  upon  dogs  by  Gouty, 
Guimaraes,  and  Niobey,81  it  is  affirmed  as  a  uniform  result  that  the  use  and  assimi- 
lation of  nitrogenous  food  were  greatly  increased,  that  the  carbonic  acid  and  oxygen 
in  the  blood  were  markedly  decreased,  and  that  the  proportion  of  sugar  and  of 
urea  in  the  blood  was  notably  increased. 

In  the  face  of  so  much  contradiction  it  is  perhaps  wisest  to  reserve 
opinion,  but  it  does  seem  as  though  the  present  evidences  warranted  the 
conclusion  reached  by  E.  Perisot M  that  the  action  of  caffeine  upon  urea- 
elimination  and  upon  protoplasmic  change  is  inconstant,  and  not  direct 
and  pronounced.  It  is  true  that  in  a  long  series  of  very  elaborate  calori- 
metrical  experiments  performed  by  E.  T.  Reichert M  it  seems  to  have  been 
proved  that  caffeine  increases  the  heat-production  as  well  as  the  heat- 
dissipation,  and  that  of  these  phenomena,  the  increase  of  the  heat-pro- 
duction is  probably  primary.  This  result  is  in  accord  with  that  of  Wil- 
helm  Heerlein,*4  who  found  marked  increase  in  the  consumption  of  oxygen 
and  formation  of  carbonic  acid  produced  under  the  influence  of  caffeine. 
Nevertheless,  these  united  results,  if  their  accuracy  be  accepted,  do  not 
show  that  destructive  metamorphosis  of  nitrogenous  tissue  is  increased 


CARDIAC   STIMULANTS.  347 

by  caffeine,   but  only  that  there  is  an  increased  destruction  of    carbo- 
hydrates. 

SUMMARY. — Caffeine  is  a  powerful  stimulant  to  those  cells  of  the 
cerebral  cortex  which  are  functionally  connected  with  consciousness 
and  intellectual  action.  It  is  also  mildly  stimulating  to  the  respiratory 
centres  and  probably  to  the  motor  cells  of  the  spinal  cord,  but  seems 
to  be  without  action  upon  the  nerve-trunks.  It  is  a  powerful  muscle- 
poison,  at  first  producing  a  condition  in  which  there  is  exaggerated 
muscular  excitability,  with  a  tendency  to  tetanic  contractions  upon 
momentary  stimulation,  and  afterwards  a  stage  of  stiffness,  weakness, 
and,  finally,  lost  excitability.  It  is  a  mild  stimulant  to  the  circulation ; 
probably  by  virtue  of  its  relation  to  the  muscle-fibres  it  increases  the 
cardiac  force  and  perhaps  also  directly  contracts  the  arterioles.  In 
overdose  it  depresses  the  circulation,  probably  acting  both  upon  the 
heart  and  the  blood-vessels.  It  is  absorbed  with  rapidity,  and  is  to 
some  extent  decomposed  in  the  body,  and,  at  least  in  part,  eliminated 
through  the  kidneys,  upon  whose  secreting  structure  it  exerts  a  marked 
stimulating  influence.  Although  the  evidence  is  contradictory,  it  is  not 
at  present  •writing  probable  that  caffeine  has  any  distinct  specific  in- 
fluence upon  protoplasmic  nutrition,  but  it  does  appear  to  directly 
increase  the  production  of  carbonic  acid  and  of  animal  heat. 

THERAPEUTICS. — In  accordance  with  its  physiological  action,  caffeine 
is  employed  in  practical  medicine  as  a  cerebral  and  cardiac  stimulant.  It 
is  often  taken  to  produce  wakefulness  and  increase  the  mental  power 
during  excessive  work.  It  is  a  valuable  remedy  for  the  relief  of  'migraine 
and  other  forms  of  nervous  headaches,  in  which  its  effects  are  sometimes 
marvellous,  although  more  often  it  fails  to  accomplish  good.  To  predict 
in  any  case  what  its  influence  will  be,  in  the  present  state  of  our  clinical 
knowledge,  is  impossible  ;  but  the  remedy  may  always  be  tried  in  safety 
in  the  dose  of  five  grains,  taken  when  the  paroxysm  is  coming  on,  and 
repeated  in  half  the  quantity  once  in  forty  minutes  if  necessary.  It 
is  in  these  cases  especially  effective  in  combination  with  phenacetin  (pro- 
portion five  grains  to  fifteen  grains).  In  opium-poisoning,  either  in  the 
form  of  unlimited  quantities  of  a  strong  decoction  of  coffee  or  of  the  alka- 
loid itself,  it  is  a  standard  remedy,  acting  by  promoting  wakefulness  and 
stimulating  the  respiration. 

J.  Hughes  Bennett  found  that  the  exhibition  of  from  four  to  four  and  a  half 
grains  of  caffeine  would  save  a  proportion  of  cats  poisoned  with  the  previously 
ascertained  minimum  lethal  dose  (one  and  seven-eighths  grains)  of  morphine. 
Several  of  the  cats  which  had  thus  been  saved  succumbed  some  days  afterwards  to 
one  and  seven-eighths  grains  of  morphine.  The  caffeine  was  powerless  to  save 
animals  to  which  larger  doses  of  the  narcotic  had  been  given. 

We  have  had  no  experience  with  the  use  of  caffeine  as  a  general 
stimulant  in  acute  adynamia,  but  various  French  authors  recommend  the 
remedy  very  highly,  and  H.  Huchard35  especially  commends  it  in  typhoid 
fever,  asserting  that  it  relieves  not  only  the  adynamia,  but  also  acts  as  an 
antipyretic,  and  through  its  diuretic  influence  is  especially  useful  when 
the  urine  is  scanty  and  albuminous. 


348  GENERAL  REMEDIES. 

Caffeine  is  valuable  as  a  cardiac  stimulant  in  the  treatment  of  all 
forms  of  heart-failure.  The  statement  of  Gubler  that  it  acts  as  a  powerful 
diuretic  is  also  undoubtedly  correct.  The  indications  for  its  employment 
are  precisely  those  which  call  for  the  use  of  digitalis,  but  it  meets  these 
indications  with  much  less  certainty  than  does  that  drug.  Caffeine,  un- 
like the  digitalis  group,  finally  paralyzes  the  heart,  and  therefore  does 
not  compare  as  a  cardiac  stimulant  in  power  and  completeness  of  action 
with  digitalis  or  strophanthus,  belonging  rather  with  ammonia  and  alco- 
hol. It  is,  however,  more  prompt  and  fugacious  in  its  action  than  is 
digitalis,  and  much  more  actively  diuretic  ;  and  is,  therefore,  especially 
useful  when  there  are  pronounced  dropsical  symptoms.  In  chronic 
Bright  s  disease  it  is  often  of  service,  especially  in  the  latter  stages,  when 
there  is  marked  cardiac  failure.  In  acute  Bright1  s  disease  it  should  be 
employed  with  caution,  if  at  all.  It  is  superior  to  digitalis  in  never  dis- 
agreeing with  the  stomach  and  in  having  no  distinct  cumulative  tendency. 
In  some  cases,  however,  it  produces  obstinate  wakefulness,  and  we  have 
occasionally  found  it  necessary  to  give  it  solely  in  the  early  part  of  the 
day.  It  is  usually  best  to  commence  with  a  dose  of  four  grains,  given 
twice  daily,  increased  if  necessary  to  twenty  or  twenty-five  grains  a  day. 
For  internal  administration  the  citrated  caffeine  is  often  preferred  on  ac- 
count of  its  solubility.  When  great  promptness  of  action  is  required,  as 
in  cases  of  sudden  collapse  or  of  sudden  cardiac  failure ',  the  hypodermic 
use  of  caffeine  suggests  itself.  Unfortunately,  the  ordinary  salts  are 
decomposed  in  the  presence  of  water,  and  are,  therefore,  ineligible  for 
hypodermic  use.  The  sodium  and  caffeine  benzoate  has  been  proposed 
as  moderately  stable  and  free  from  irritating  properties.  One  equivalent 
of  sodium  salicylate  (160  parts)  will  also  cause  the  solution  of  one  equiva- 
lent of  caffeine  (244  parts),  and  the  following  formula  has  been  com- 
mended by  Tanret  for  hypodermic  use  :  sodium  salicylate,  thirty-one 
parts  ;  caffeine,  forty  parts  ;  distilled  water,  sixty  parts. 

TOXICOLOGY. — The  only  case  of  poisoning  by  caffeine  that  we  have 
met  with  is  reported  by  C.  H.  F.  Routh.86  An  adult  took  a  drachm  of  the 
so-called  citrate.  The  symptoms  developed  at  once  ;  they  were  burning  in 
the  throat,  giddiness,  faintness,  nausea,  numbness  and  tremors  of  the  ex- 
tremities, pain  in  the  stomach  and  bowels,  profuse  diuresis,  and  finally 
collapse,  with  cardiac  oppression  and  icy  extremities.  Consciousness 
was  not  impaired,  and  there  was  no  headache  until  the  patient  began  to 
recover.  In  a  case  reported  by  Curschmann,37  a  woman,  in  order  to 
produce  an  abortion,  took  a  decoction  made  from  about  eight  ounces  of 
freshly  roasted  coffee.  Two  hours  later  she  was  found  in  a  condition  of 
great  anxiety,  with  a  sensation  of  intense  need  for  air  ;  she  was  exceed- 
ingly restless,  and  continually  attempted  to  get  up  from  her  chair,  but 
was  powerless  to  do  so.  All  the  extremities,  but  especially  the  hands, 
were  affected  with  very  pronounced  choreic  tremors.  She  knew  persons 
and  her  surroundings,  but  her  cerebration  was  very  much  affected,  and 
the  next  day  she  remembered  nothing  that  had  happened  at  this  time. 


CARDIAC   STIMULANTS.  349 

The  respiration  was  quick,  24  and  25  per  minute,  and  short ;  the  pulse 
112  ;  the  heart-beats  very  strong,  even  violent.  One  hour  after  the  in- 
gestion  of  the  dose  violent  diarrhoea  set  in,  and  continued  until  the  next 
day.  The  passages  were  very  thin  and  watery,  with  but  little  violent 
pain,  but  much  tenesmus.  There  was  also  marked  tenesmus  of  the 
bladder.  The  urine  was  greatly  increased  in  quantity,  with  a  specific 
gravity  of  1014.  P.  B.  Wing38  has  reported  a  case  of  amblyopia  produced 
by  the  excessive  use  of  coffee. 

CONVALLARIA.     U.  S. 

In  1859  G.  F.  Walz  discovered  in  the  lily  of  the  -valley  (Convallaria 
majalis,  the  rhizome  and  roots  of  which  are  official)  two  active  sub- 
stances, Convallarin  and  Convallamarin.  Of  these,  the  first  is  crystal- 
line, insoluble  in  water,  and,  according  to  W.  Marme,1  when  taken  in 
doses  of  three  or  four  grains,  acts  as  a  simple  purgative.  The  glucoside 
convallamarin  is  soluble  in  water,  and  is  the  principle  to  which  the  plant 
owes  its  action  upon  the  circulation.  Marme  found  that  it  kills  by  a 
direct  action  upon  the  heart,  and  in  moderate  doses  first  slows  and  then 
quickens  the  pulse  :  previous  division  of  the  vagi  did  not  interfere  with 
the  development  of  these  phenomena.  See 2  finds  that  in  the  dog  it  first 
slows  the  action  of  the  heart  and  increases  the  blood-pressure  decidedly, 
the  respirations  at  the  same  time  becoming  fuller  and  a  little  less  frequent. 
If  a  toxic  dose  has  been  given,  the  heart's  beats  become  very  rapid  and 
irregular,  the  arterial  pressure  still  being  much  above  normal  ;  finally 
the  pressure  begins  to  fall,  the  cardiac  pulsations  to  grow  more  feeble, 
and  death  occurs  through  syncope.  It  is  stated  that  the  pneumogastric 
nerves  are  weakened  but  never  paralyzed,  while  the  general  nervous 
system  is  not  affected.  In  man  the  action  of  the  drug  upon  the  circula- 
tion is  as  in  the  lower  animals,  and  there  is  said  to  be  usually  produced 
profuse  diuresis  and  sometimes  purging.  In  Isaew's  experiments  upon 
frogs  with  convallamarin,  the  heart  was  arrested  in  ventricular  systole  by 
two  milligrammes  of  the  pure  convallamarin,  the  frog  continuing  to  live 
for  a  long  time,  the  remedy  seemingly  having  no  effect  upon  its  general 
nervous  or  muscular  system  ;  isolating  the  heart  had  no  effect  upon  the 
action  of  the  poison. 

The  fact  that  the  heart  is  arrested  in  systole  by  convallamarin  has  been 
confirmed  in  the  frog  by  Coze  and  Simon,3  in  the  dog  by  I.  Ott,4  and  it 
would  appear,  therefore,  that  the  drug  is  a  cardiac  stimulant,  more  or 
less  similar  to  digitalis  in  its  action.  Unfortunately,  however,  See  affirms 
that  in  the  dog  the  heart  is  arrested  in  diastole,  that  organ  not  being 
able  to  respond  to  the  most  powerful  galvanic  stimulant ;  Leubuscher 
states  that  convallamarin  causes  in  the  frog  systolic  cardiac  arrest,  but 
diastolic  cardiac  arrest  in  the  mammal  :  and  further,  that  in  no  doses 
does  it  in  the  mammal  elevate  the  arterial  pressure  ;  whilst  Leo  Lowen- 
thal,5  using  the  same  preparation  in  exactly  the  same  manner  and  dose 
upon  different  frogs  of  the  same  species,  obtained  diverse  results  which 


350  GENERAL  REMEDIES. 

he  himself  was  at  a  loss  to  explain.  The  evidence  is  so  contradictory 
as  to  suggest  that  different  observers  have  used  different  substances 
under  one  name.  J.  Nathanson6  asserts  that  the  confusion  is  largely 
due  to  the  impurity  and  lack  of  genuineness  in  the  products  used,  even 
Merck  himself  having  admitted  that  his  commercial  convallamarin  is  not 
the  pure  principle.  Nathanson  found  that  convallarin  produced  in  man 
when  given  in  doses  of  0.06  to  0.12  gramme  three  or  four  times  daily 
only  nausea,  diarrhoea,  and  gastric  pain  ;  while  convallamarin  adminis- 
tered in  daily  amounts  gradually  increasing  from  0.03  to  0.3  gramme 
reduced  the  rate  of  the  pulse  and  markedly  increased  the  flow  of  urine, 
only  in  very  rare  cases  causing  nausea  or  vomiting. 

THERAPEUTICS. — The  lily  of  the  valley  is  said  to  have  been  long  used 
by  the  Russian  peasantry  for  the  relief  of  dropsy,  and  in  1880  Troitzky 
and  Bojojawlewsky  7  called  attention  to  it  as  a  valuable  remedy  in  cardiac 
valvular  disease,  especially  when  associated  with  dropsy.  S6e  recommends 
it  in  palpitation  of  the  heart,  cardiac  dilatation,  fatty  degeneration,  and 
other  forms  of  cardiac  weakness,  also  in  valvular  lesions  with  failing 
heart-power  ;  in  a  word,  in  the  class  of  cases  in  which  digitalis  is  now 
used.  When  there  is  dropsy,  its  positive  diuretic  action  renders  it  es- 
pecially valuable,  and  in  some  cases  it  purges  freely,  probably  through 
the  convallarin.  The  value  of  the  remedy  has  been  confirmed  by  H.  Des- 
plats8  and  by  several  other  practitioners.  Although  condemned  after 
trial  by  B.  Stiller,9  by  Pel,10  by  Leyden,11  by  Jacobi  and  Lubilinski,1'2  and  by 
G.  Leubuscher,  it  has  been  highly  praised  by  Silvestrini 13  and  by  E.  Mara- 
gliana. 14  E.  Sansom 15  gives  as  the  result  of  his  experience  that  conval- 
lamarin is  very  useful  in  mitral  stenosis  with  failing  of  the  heart.  Marme 
found  that  the  fatal  dose  of  convallamarin  was,  for  the  dog,  0.015-0.03 
gramme  ;  for  the  cat,  0.005  gramme  ;  for  the  rabbit,  0.006-0.008  gramme. 
S6e  gives,  of  an  aqueous  extract  of  the  whole  plant,  from  fifteen  to 
twenty- three  grains  a  day  ;  Bojojawlewsky,  each  day  an  infusion  repre- 
senting from  fifty  to  one  hundred  grains  of  the  plant.  The  U.  S.  Phar- 
macopoeia recognizes  a  fluid  extract  only  (FLUIDEXTRACTUM  CONVAL- 
LARIJE,  U.  S. ),  the  dose  of  which  is  from  five  to  fifteen  minims  (0.3-0.9 
C.c. ).  The  results  obtained  by  Nathanson  show  that  great  caution  must 
be  exercised  in  the  practical  use  of  the  active  principles  of  convallaria. 

SPARTEINE. 

Sparteine  is  a  liquid  alkaloid  obtained  from  the  Cytisus  Scoparius,  or 
common  broom  plant.  (See  SCOPARIUS.)  It  is  colorless,  of  a  pene- 
trating odor  and  extremely  bitter  taste,  soluble  in  alcohol,  in  ether,  and 
in  chloroform.  Sparteine  sulphate  (SPARTEIN^E  SULPHAS,  U.  S. )  occurs 
in  colorless  prismatic  crystals  or  granular  powder,  freely  soluble  in  water 
and  in  alcohol,  having  a  neutral  reaction  and  a  bitter,  slightly  saline  taste.* 

*  The  hydrochlorate  of  oxy Sparteine,  an  oxidation  product  from  sparteine,  is  freely 
soluble  in  water,  and  has  been  used  with  asserted  good  results  hypodermically  by  Von 
Oefele,  in  dose  of  six-tenths  of  a  grain,  as  an  active  cardiac  stimulant.  See  K.  Hurthle 
(Arch.f.  Exper.  Path.  u.  Pharm.,  1892). 


CARDIAC   STIMULANTS.  351 

PHYSIOLOGICAL  ACTION. — The  ordinary  therapeutic  dose  of  sparteine 
produces  no  very  definite  symptoms,  but  Legris  found  that  in  doses  of 
thirty  centigrammes  or  over  the  alkaloid  caused  vertigo,  headache,  palpi- 
tations, and  formications  in  the  extremities  ;  whilst  Garand  noted  that 
forty  centigrammes  produced  decided  cardiac  pain,  with  paraplegic 
paresis,  these  symptoms  appearing  about  twenty  minutes  after  the  injec- 
tion of  the  alkaloid,  and  reaching  their  maximum  in  from  four  to  five  hours. 

In  the  lower  animals  sparteine  in  large  doses  causes  marked  nervous  dis- 
turbances. (See  Husemann,1  Mitchell,  Schroff,  De  Rymon,  Griffe,  and  others.) 
There  appear  to  be  two  stages  of  the  poisoning.  The  first  of  these  is  characterized 
by  trembling,  incoordination  of  movements,  increase  of  reflexes,  clonic  and  tonic 
convulsions,  embarrassment  of  respiration,  acceleration  of  the  pulse,  and  enfeeble- 
ment  of  the  heart ;  the  second,  by  enfeeblement  of  all  the  functions,  the  respiration 
becoming  more  and  more  depressed,  and  death  preceded  by  convulsions  occurring 
from  respiratory  paralysis.  Kick  found  that  by  artificial  respiration  life  may  be 
prolonged  for  a  very  considerable  period. 

Nervous  System. — The  conclusions  reached  by  experimental  physi- 
ologists in  regard  to  the  action  of  sparteine  upon  the  nervous  system  are 
so  contradictory  as  to  imply  that  different  alkaloids  have  been  used  under 
one  name. 

According  to  Pick2  and  Mitchell,  sparteine  has  a  distinct  influence  upon  the 
cerebrum  ;  and  Pick,  Gluzinski,3  and  other  observers  have  found  that  the  loss  of 
reflex  activity  and  the  fatal  arrest  of  respiration  are  due  to  centric  paralysis  ;  whilst 
De  Rymon,4  Griffe,5  and  Gluzinski  are  in  accord  in  affirming  that  neither  the  motor 
nor  sensory  nerves  are  affected.  In  this  they  are  confirmed  by  Cerna,  who  even 
states  that  the  local  application  of  strong  solutions  has  no  sensible  effect  upon  the 
nerves.  On  the  other  hand,  Pick  and  Mitchell  state  that  the  motor  nerves  are 
attacked,  and  A.  R.  Cushny  and  S.  A.  Matthews6  find  that  sparteine  is  closely 
related  in  its  physiological  action  to  conium,  its  chief  influence  being  upon  the 
peripheral  motor  nerve-endings  in  the  muscle,  whereby  it  causes  a  paralytic 
asphyxia.  Guinard  and  Geley '  state  that  sparteine  locally  applied  paralyzes  the 
sensory  nerves  in  the  eye,  and  may  even  be  substituted  for  cocaine  in  operations 
upon  the  eye. 

The  conclusion  reached  by  Muto  and  Ishizaka 21  that  the  fatal  failure 
of  respiration  of  sparteine-poisoning  is  due  to  the  depressing  action  of  the 
drug  upon  the  peripheral  phrenic  nerve  as  well  as  to  an  action  upon  the 
respiratory  centres,  is  in  accord  with  the  present  probabilities,  namely, 
that  the  alkaloid  has  both  a  centric  and  a  peripheral  paralyzing  action. 

Circulation. — Although  the  subject  of  the  action  of  sparteine  upon  the 
circulation  has  been  investigated  by  Laborde,8  Griffe,  Garand,9  Masius,10 
Gluzinski,11  Cerna,12  A.  R.  Cushny  and  S.  A.  Matthews,  the  results 
reached  have  been  so  discordant  as  to  make  their  reconcilation  at  present 
impossible.  The  chief  facts,  that  seem  to  us  to  be  fixed,  are  that  a 
sufficient  dose  of  the  alkaloid  produces  a  pronounced  fall  of  the  arterial 
pressure,  which  is  at  least  in  part  due  to  a  direct  action  of  the  drug  upon 
the  heart.  The  more  important  question,  whether  the  small  dose  of 


352  GENERAL  REMEDIES. 

sparteine  is  or  is  not  a  cardiac  stimulant,  cannot  at  this  time  be  finally 
answered. 

The  effect  of  the  alkaloid  upon  the  pulse-rate  in  its  fullest  serial  development 
appears  to  be  a  primary  slowing,  followed  by  an  acceleration,  which  in  turn  gives 
way  to  a  pronounced  decrease  below  the  normal.  The  size  of  the  dose  is  a  very- 
potent  factor  in  determining  the  action  on  the  pulse-rate  ;  thus,  if  a  very  large  dose 
is  given  the  pulse  at  once  becomes  slow  and  remains  slow.  Again,  the  slowing 
before  acceleration  of  the  pulse  has  not  been  noted  by  various  observers,  and  prob- 
ably occurs  only  after  very  small  doses,  and  in  some  cases,  according  to  the 
researches  of  Gluzinski,  it  is  due  to  a  primary  excitement  of  the  vagi  nerve.  Pick, 
Griffe,  Garand,  Masius,  Gluzinski,  and  Cushny  and  Matthews  are  in  accord  in 
stating  that  the  acceleration  of  the  pulse  is  due  to  peripheral  paralysis  of  the  pneu- 
mogastric  nerves,  with  its  consequent  withdrawal  of  inhibition,  whilst  it  seems  to 
be  proved  that  the  final  slowing  of  the  pulse  is  the  outcome  of  a  direct  impulse  of 
the  sparteine  upon  the  heart  itself.  Neither  muscarine  (Pick)  nor  atropine  (Cushny 
and  Matthews)  prevents  the  action  of  sparteine  upon  the  heart. 

Garand,  Gluzinski,  Pawlow,  and  Cerna  all  affirm  as  the  result  of  their  own 
experiments  that  there  is  a  distinct  primary  stage  of  increased  arterial  pressure  ; 
and  in  the  experiments  of  Cushny  and  Matthews  such  rise  of  pressure  immediately 
followed  the  injection  of  five  milligrammes  of  the  alkaloid  into  the  veins  of  rabbits 
and  cats,  whether  they  had  or  had  not  been  paralyzed  with  curare  or  other  drugs. 
According  to  Pawlow,  this  rise  of  blood-pressure  is  due  chiefly  to  stimulation  of  the 
vaso-motor  centres  ;  whilst  Cerna  reached  the  conclusion  that  it  is  caused  partly  by 
an  increased  activity  of  the  heart  and  partly  by  centric  vaso-motor  stimulation. 
Cerna  compares  the  action  of  sparteine  to  that  of  digitalis.  Cushny  and  Matthews 
conclude  that  sparteine  is  entirely  apart  from  digitalis  in  that  it  does  not  prolong 
systole,  but  slows  the  pulse  simply  by  increasing  diastole  ;  and  in  that  it  favors 
excessive  dilatation  of  the  heart,  and  in  any  dose  is  a  sedative  rather  than  a  stimu- 
lant to  the  viscus.  They  find  that  in  the  mammal  the  rise  of  blood-pressure  is  very 
brief  and  does  not  occur  when  the  drug  is  given  by  the  stomach.  They  conclude 
that  the  rise  is  not  due  to  any  specific  influence  of  the  sparteine,  but  is  called  forth 
by  local  irritation. 

Muscles. — When  applied  locally  to  the  muscles,  sparteine  has  some 
influence  in  diminishing  their  excitability  and  prolonging  the  duration  of 
the  latent  period  (De  Rymon,  Griffe,  and  Gluzinski).  But  it  does  not 
destroy  the  functional  activity  of  the  muscles,  even  when  brought  in 
direct  contact  with  them  in  a  concentrated  form,  and  its  muscular 
influence  is  too  feeble  to  be  manifested  in  general  poisoning. 

Kidneys. — It  is  still  doubtful  whether  sparteine  does  or  does  not  fully 
represent  the  diuretic  influence  of  scoparius.  Griffe  affirms  that  in  his  ex- 
periments upon  rabbits  it  produced  absolute  decrease  in  the  excretion  of 
urine,  and  although  some  clinicians  assert  that  it  acts  in  a  man  as  a  dis- 
tinct diuretic,  others  affirm  that  any  increased  diuresis  is  secondary  to  the 
regulation  of  the  circulation. 

SUMMARY. — The  exact  action  of  sparteine  upon  the  nervous  sys- 
tem is  not  at  present  known.  According  to  some  observers,  it  dis- 
tinctly depresses  both  the  cerebrum  and  the  spinal  cord,  causing  death 
by  centric  paralysis  of  respiration ;  -whilst,  according  to  other  experi- 
menters, it  is  a  motor-nerve  paralyzant  and  arrests  respiration  periph- 


CARDIAC   STIMULANTS.  353 

erally.  The  probabilities  are  that  it  acts  both  centrically  and  periph- 
erally. Upon  the  muscles  its  action  is  so  feeble  as  to  be  in  no  way 
manifested  after  the  ingestion  of  poisonous  doses.  The  small  dose  may 
first  slow  the  pulse  by  stimulating  the  pneumogastric  nerve,  but  after 
a  sufficient  dose  the  pulse-rate  is  sooner  or  later  increased  by  pneumo- 
gastric paralysis,  to  be  later  diminished  by  the  direct  action  of  the 
drug  upon  the  heart  itself.  Sparteine  produces  a  very  large  pulse- 
wave,  with  a  rise  of  the  arterial  pressure  after  the  small  dose ;  this 
rise  being,  according  to  most  experimenters,  due  to  stimulation  of  the 
heart  and  of  the  vaso-motor  centres,  but  according  to  some  it  is  a 
merely  temporary  phenomenon,  the  result  of  peripheral  irritation; 
further,  the  action  of  the  alkaloid  upon  the  heart  is  likened  by  experi- 
menters to  that  of  digitalis,  but  it  is  certainly  different  in  that  the  very 
large  dose  positively  depresses  the  heart ;  moreover,  according  to  cer- 
tain investigators,  the  action  even  of  the  small  dose  is  essentially  dif- 
ferent from  that  of  digitalis,  in  that  the  diastole  alone  is  prolonged,  and 
the  tendency  is  to  enlargement  rather  than  to  contraction  of  the  heart. 
It  is  not  at  present  positively  ascertained  that  the  alkaloid  is  a  cardiac 
stimulant,  but  it  is  probable  that  it  first  stimulates  and  then  depresses 
the  viscus. 

THERAPEUTICS. — The  use  of  sparteine  in  diseases  of  the  heart  has 
been  studied  by  a  number  of  clinicians,  notably  S6e,  Garand,  Roland,13 
Voit,14  J.  M.  Clarke,15  Kurloff,16  and  Pawinski,17  who  are  all  in  accord 
in  affirming  it  to  be  of  value  in  the  treatment  of  cardiac  affections,  in 
which  it  slows  the  pulse  and  renders  it  more  regular,  increases  diuresis, 
and  is  superior  to  most  other  cardiac  remedies  in  its  power  of  controlling 
general  nervous  excitement.  Pawinski  states  that  in  pure  nervous  palpi- 
tation it  exceeds  digitalis  in  power  and  certainty  in  action,  and  that  it  is 
a  valuable  sedative  in  hysteria,  neurasthenia,  and  allied  conditions.  Both 
Pawinski  and  See  assert  that  it  has  a  remarkable  power  of  regulating  the 
heart' s  action  ;  the  latter  observer,  indeed,  affirms  that  no  known  remedy 
equals  it  for  the  purpose  of  making  an  irregular  pulse  regular.  On  the 
other  hand,  Pawinski  warns  against  its  use  in  cases  in  which  the  heart- 
muscle  is  believed  to  have  undergone  degeneration.  Its  action  is  a  rapid 
one,  the  symptoms  produced  by  it,  according  to  Clarke,  S£e,  and  others, 
developing  in  thirty  minutes  to  an  hour  after  its  ingestion,  and  continuing 
for  five  or  six  hours.  According  to  Clarke,  these  symptoms  consist  pri- 
marily of  a  marked  retardation  of  the  pulse,  with  increase  of  the  force 
and  of  the  arterial  tension,  the  skin  at  the  same  time  becoming  red  and 
moist,  while  the  respiration,  which  is  at  first  quickened,  soon  becomes 
slower  and  fuller  than  normal.  In  overdoses  it  is  said  to  cause  very  high 
tension  of  the  pulse,  with  sharp  cutting  or  throbbing  pains  in  the  cardiac 
region,  and  sometimes  nausea.  It  has  been  employed  with  asserted  ex- 
cellent results  in  all  forms  of  valvular  disease,  in  asthma,  and  especially 
in  functional  cardiac  derangements.  The  very  important  statement  made 
by  Clarke,  that  it  will  control  the  pulse-rate  and  general  symptoms  in 
Graves'  s  disease,  receives  some  confirmation  in  the  work  of  Pawinski  and 
in  our  owi\experience.  Some  clinicians,  notably  Hans  Leo,18  and  Hiero 

23 


354 


GENERAL  REMEDIES. 


Stoessel,19  have  found  sparteine,  however,  a  very  uncertain  remedy.  We 
do  not  believe  that  for  general  purposes  it  nearly  equals  digitalis  :  in  our 
own  trials  with  it  in  organic  cardiac  cases  the  results  have  been  very  un- 
satisfactory. It  may  be  useful  as  a  succedaneum  to  digitalis,  and  even 
as  a  substitute  in  neurotic  cases.  Pawinski  gives  0.016  to  0.04  gramme 
three  times  a  day,  increasing  gradually  to  0.6  gramme  during  the  twenty- 
four  hours.  The  statements  of  Guinard  and  Geley,  that  sparteine  may  be 
used  successfully  externally  like  guaiacol  for  an  antipyretic,  are  strongly 
contradicted  by  Lannois.20  The  sulphate  (SPARTEINE  SULPHAS,  U.  S. ) 
may  be  used  in  pill  or  solution  in  commencing  dose  from  one-quarter  to 
one-half  a  grain,  cautiously  increased  to  two  grains  if  required,  and  re- 
peated every  six  to  eight  hours. 

ADONIDIN. 

Adonis  vernalis,  a  plant  of  Northern  Europe  and  Asia,  contains  a  glu- 
coside  to  which  Cervello  has  given  the  name  of  adonidin.  According  to 
Cervello,1  adonidin  causes  in  the  frog  first  increase  in  the  force  of  the  sys- 
tolic contractions,  then  irregularity  of  rhythm  with  long  diastolic  pauses, 
and  finally  arrest  in  violent  systole,  the  most  characteristic  phenomenon 
being  the  peristaltic  movements  which  precede  the  cardiac  arrest.  Ac- 
cording to  H.  A.  Hare,2  adonidin  first  increases  and  then  slows  the  rate 
of  the  beat  in  the  cut-out  frog's  heart,  while  its  injection  into  the  frog  is 
followed  by  a  period  of  slowing  of  the  cardiac  movements,  with  long  dia- 
stolic pauses,  succeeded  by  great  increase  of  the  pulse- rate,  which  in  turn 
gives  way  to  slow  movement,  ending  in  arrest.  The  heart,  either  within 
or  without  the  body,  stops  in  diastole.  Although  Cervello  and  also 
Guirlet3  state  that  the  heart  is  arrested  in  systole,  Hare  affirms  that, 
whether  the  heart  be  isolated  or  in  situ,  the  arrest  is  diastolic.  The  con- 
tradiction is  not  easily  explained,  unless  it  be  through  the  observation 
of  Guirlet,  that  in  the  rabbit  he  has  seen  the  left  ventricle  in  permanent 
systolic  contraction,  with  the  other  cavities  dilated  and  full  of  blood. 
The  slowing  of  the  pulse  noted  by  Hare  was  found  by  him  to  be  due 
to  stimulation  of  the  pneumogastrics,  as  it  was  prevented  by  their  section. 
That  the  diastolic  arrest  was  not  merely  an  occasional  phenomenon  the 
result  of  excessive  inhibition,  as  is  sometimes  seen  from  digitalis,  was  proved 
by  its  occurring  after  section  of  the  vagi,  as  well  as  by  the  fact  that  gal- 
vanization of  these  nerves  in  the  later  stages  of  the  poisoning  failed  to 
inhibit  the  heart,  the  nerves  appearing  to  be  paralyzed. 

In  Hare's  experiments  adonidin  increased  very  distinctly  the  arterial 
pressure  in  the  dog,  while  decreasing  the  pulse-rate.  After  large  doses 
the  first  rise  is  followed  by  a  marked  fall  of  arterial  pressure,  with  irregu- 
larity of  the  heart's  action,  and  finally  diastolic  arrest.  The  experiments 
of  Cervello  and  of  Bubnow 4  are  in  accord  with  those  of  Hare  in  showing 
that  the  drug  produces  first  rise  and  then  fall  of  pressure.  Hare  found 
that  in  animals  whose  spinal  cord  had  been  previously  cut,  a  rise  of 
pressure  followed  the  exhibition  of  adonidin,  but  was  not  so  great  as  in 


CARDIAC   STIMULANTS. 


355 


the  normal  dog,  so  that  it  is  possible  that  the  drug  acts  as  a  stimulant 
not  only  on  the  heart  but  also  on  the  vaso-motor  system.  The  first  slow- 
ing of  the  pulse,  according  to  Hare,  is  the  result  of  stimulation  of  the 
inhibitory  nerves,  since  it  was  prevented  by  their  previous  section,  while 
the  final  fall  of  pressure  is  at  least  in  part  due  to  the  vaso-motor  palsy, 
since  neither  galvanization  of  the  sciatic  nerve  nor  asphyxia  had  any 
effect  at  a  time  when  the  heart  had  still  considerable  power. 

THERAPEUTICS. — In  1879  Adonis  vernalis  was  introduced  to  the 
medical  world  as  a  cardiac  stimulant  by  Bubnow,  a  pupil  of  Botkin. 
Since  then  it  has  been  tested  by  a  number  of  physicians,  with  fairly  con- 
cordant results.  The  general  testimony  is  that  its  action  in  disease  re- 
sembles that  of  digitalis,  and  that  it  is  useful  in  the  same  class  of  cases. 
It  is  much  more  prompt  than  is  digitalis,  and  Durand  affirms  that  it  has 
no  cumulative  tendency.  There  has  been  some  difference  of  opinion  in 
regard  to  its  diuretic  action,  and  whatever  of  such  influence  it  has  must 
be  attributed  to  its  action  upon  the  circulation  in  the  kidneys  rather  than 
to  any  marked  direct  power  over  the  secreting  structure.  Durand  asserts 
that  it  never  produces  disturbances  of  the  alimentary  canal,  but  Lublinski 
and  Huchard  have  both  seen  it  produce  so  much  vomiting  or  diarrhoea  as 
to  require  its  withdrawal.  In  a  case  reported  by  Durand  in  which  by 
mistake  three  grains  of  adonidin  were  given  every  half- hour,  violent 
vomiting  and  diarrhoea  were  the  most  troublesome  symptoms.  Bubnow 
employed  the  infusion  made  from  the  whole  herb  four  to  eight  parts  in 
one  hundred  and  eighty  parts  of  water,  and  of  this  he  administered  a 
tablespoonful  every  two  hours.  Durand  gives  the  dose  of  adonidin  as 
0.02  centigramme  (one- third  of  a  grain)  every  three  or  four  hours. 


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356 


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65.  WARREN     .   .    .   .  J.  P.,  1892,  xiii. 

66.  SCHEFFER  .   .   .   .  A.  E.  P.  P.,  1900,  Bd.  44. 

67.  ATWATER  and  BENEDICT  .  M.  N.  A.  S.,  1902, 

vii. 

68.  NEUMANN  .   .   .   .  M.  M.  W.,  1901,  xlviii. 

69.  SPIRO M.  M.  W.,  1901. 

70.  GREHANT    .   .   .   .  C.  R.  S.  B.,  1903,  Iv. 

71.  HARRINGTON  and   WALKER  .  B.    M     S.   J., 

1903.  »• 

72.  WELCH B.  M.  S.  J.,  1903.  i. 

73.  LAITINEN  (Fraenkel)  .  Ther.  Geg.,  1901,  iii. 

74.  LEE  and  SALANT  .  A.  J.  P.,  1902,  viii. 

75.  SWIENTOCHOWSKY  .  M.  M.  W.,  1903. 

76.  STORCK N.  O.  M.  J.,  Dec.  1901. 

77.  ROSENFELD   .   .   .  Ther.  Geg.,  1900,  vii. 

78.  BINZ V.  C.  M.,  1888. 

79.  HARE  and  PENNINGTON  .  T.  G.,  1903. 

80.  GRUBER W.  K.  W.,  1901. 

81.  DOYEN A.  de  P.,  1885. 

82.  THOMAS A.  E.  P.  P.,  xxxii. 

83.  ABBOTT J.  Ex.  M.,  i. 

84.  DELEARDE     .   .   .  A.  I.  P.,  1897,  ix. 

85.  LAITINEN   .   .   .   .  Z.  F.  H.,  xxxiv. 

86.  PAWLOWSKY  .   .   .  Z.  F.  H..  xxxiii. 

87.  GRUBER  and  KOEGLER  .  W.  K.  W.,  1901. 

88.  GOLDBERG  ....  Cb.  f.  B.,  xxx. 

89.  AUSEMS Cb.  I.  M.,  1902. 

90.  CABOT Tr.  American  Assoc.  Phy- 

sicians, 1903,  xviii. 

91.  MARTIN M.  M.  J.,  x.  292. 

92.  HEMMETER  .   .   .  J.  H.  B.  L.,  iv. 

93.  KOCHMANN    .   .   .  A.  I.  P.  T.,  1904-5,  xiii.  329. 

94.  WOOD  and    HOYT  .  Mem.    Nat.    Acad.    Sci. 

1905,  x. 

95.  LOEB     ......  In.  Dis.,  Heidelberg,  1905. 

METHYLIC  ALCOHOL. 

1.  JELLIFFE    .   .   .   .  M.  News,  1905.  Ixxxvi.  387. 

2.  BlRCH-HlRSCHFELD     .     Versamml.      Ophth. 

Gesell.  Heidelberg,  1900. 

3.  HUNT Johns    Hopkins    Hospital 

Report.,  Aug.  and  Sept. 
1900. 

DIGITALIS. 

1.  NATIVELLE    .  .   .  B.  A.  M.,  1871,  xxxvi. 

2.  ARNOLD  and  WOOD  .  A.  J.  M.  S.,  1900. 

3.  ROGER C.  R.  S.  B.,  1889,  i. 

4.  WEIL A.  A.  P.,  1871,  252. 

5.  MEIHUIZEN    .   .   .  A.  G.  P.,  1873,  vii. 

6.  DYBKOWSKY    and    PELIKAN  .  Zeit.    f.    Wis- 

sensch.  Zoolog.,  1862,  xi. 

7.  GOURVAT    ....  Gazette    Med.    de    Paris, 

1871. 

8.  BOEHM     A.  G.  P.,  1872,  v. 

9.  BRUNTON    .   .   .   .  On  Digitalis,  London,  1868. 

10.  WILLIAMS  .   .   .   .  A.  E.  P.  P.,  xiii.  i. 

11.  SCHMIEDEBERG    .  Beitr.  z.  Anat.  u.  Physiol., 

Ludwig's  Festgabe. 

12.  FRANCK Journ.    de   Med.  de    Bor- 

deaux, xi.  67. 

13.  DONALDSON  and  STEVENS  .  J.  P.,  1883,  iv.  165. 

14.  CUSHNY J.  Ex.  M.,  1897,  ii. 

15.  FOTHERGILL  .   .   .  Digitalis,  London,  1871. 


CARDIAC   STIMULANTS. 


357 


REFERENCES.—  Continued. 


16.  ACKERMANN  .    .    .  B.  K.  \V.,  1872,  ix.  27. 

17.  BRUNTON  and  TUNNICLIFFE  .  J.  P.,  xx.  354. 

18.  RINGER  and  SAINSBURY  .  M.  C.  Tr.,  Ixvii. 

19.  KOBERT T.  G.,  1887,  iii. 

20.  GOTTLIEB  and  MAGNUS  .  A.  E.  P.  P.,  xlvii., 

xlviii. 

21.  BORDIER B.  G.  T.,  1868,  no. 

22.  PAUL B.  G.  T.,  1868,  193. 

'23.  LOR  RAIN     .   .   .   .  J.  de  1'A.  P.,  1870. 

24.  HAMMOND  ....  Proc.      Acad.     Nat.     Sci. 

Phila.,  Dec.  1858. 

25.  HOMOLLE   ....  A.  G.  M.,  July,  1861. 

26.  WlNOGRADOFF       .  V.  A.  P.  A.,  l86l,  xxii. 

27.  STADION Prager      Vierteljahrs.      f. 

Prakt.  Heilk.,  i862,lxxii. 

28.  MEUSNIER  ....  Thesis,  Paris,  1868. 

29.  KAUFMANN    .   .    .  Rev.  de  M£d.,  iv. 

30.  ALEXEEVSKY     .   .  In.    Dis.,    St.    Petersburg, 

1890. 

31.  BELJAKOW  ....  S.  Jb.,  1891,  ccxxix. 

32.  LEGROS Thesis,  1867. 

33.  COBLENTZ  ....  Thesis,  Strasburg,  1862. 

34.  DA  COSTA  .   .   .   .  A.  J.  M.  S.,  Jan.  1871. 

35.  HARE  and  COPLIN  .  T.  G..  1897,  xiii. 

36.  DOBIE B.  M.  J.,  Dec.  1872. 

37.  WUNDERLICH    .   .  Medical        Thermometry, 

Syd.  Soc.  Trans.,  325. 

38.  WINKEL P.  M.  T.,  1874,  iv. 

39.  DICKENSON    .   .   .  M.  C.  Tr.,  xxix. 

40.  STADION Syd.  Soc.  Year-Book,  1862, 

45i- 

41.  GAUNOT P.  M.  T.,  iv,  30. 

42.  HALL Amer.  Med.,  June,  1901. 

43.  TARDIEU     ....  CKnique,  Paris,  1867. 

44.  G.  H.  M  C.,July,  1874. 

45.  ZUGSMITH  ....  Amer.  Med.,  1901. 

46.  KOHNHORN    .   .   .  L.  L.,  1876,  i.  583. 

47.  P.  M.  T.,  ii.  24. 

48.  BRUNTON  and  CASH  .  Pract.,  xxxiii.  272. 

49.  FR^ENKEL      .   .   .  A.  E.  P.  P.,  li.  84. 

50.  BEATES J.  A.  M.  A.,  1897,  xxviii. 

1209. 

51.  ARNOLD  and  WOOD,  JR.  .  A.  J.  M.  S.,  August, 

1900. 

52.  ZELTNER     .   .   .  .  G.  I.  M.  P.,  1900. 

53.  CURIONI Cl.  M.  I.,  1901. 

54.  PENZOLDT  ....  G.  I.  M.  P.,  1900,  No.  8. 

55.  BOSSE S.  J.,  cclxx. 

56.  HUGHES A.  J.  P.,  1899. 

57.  HUCHARD   .   .   .   .  J.  Pr.,  xvi.  1902. 

APOCYNUM. 

1.  SCHMIEDEBERG     .  A.  E.  P.  P.,  1883,  XVI.  l6l. 

2.  DOTSCHEWSKI  .   .  Wiener  Klin.  Rundschau, 

1895,  ix.  929. 

3.  WOOD,  JR J.  A.  M.  A.,  Dec.  24,  1904. 

4.  GRISCOM    .  .  .  .  A.  J.  M.  S.,  1833. 

5.  DABNEY T.  G..  1898,  xiv.  730. 

6.  LOWRY N.  Y.  M.  J.,  1884,  Ix.  472. 

7.  GRISCOM A.  J.  M.  S.,  1833,  xii.  55. 

STROPHANTHUS. 

1.  GLHY C.  R.  S.  B.,  1889. 

2.  MAYEUR Thesis,  Lille,  1888. 

3.  LEMOINE    .  .   .  .  C.  R.  S.  B.,  1888,  v. 

4.  FRASBR J.  A.  P.,  vii.  141 ;  B.  M.  J., 

1885,  ii. 

5.  BAHADHURJI  .  .  .  B.  M.  J.,  1887,  ii. 


6.  MAIRET  and  COMBEMALE.  C.  R.  S.  B.,  1887,  iv. 

7.  HUCHARD   ....  Thesis,  Paris,  1888. 

8.  GLEY  and  LAPICQUE  .  C.  R.  S.  B.,  1887. 

9.  POPPER C.  M.  W.,  1888,  xxvi. 

10.  PASCHKIS  and  ZERNER  .  Med.  Jahrb.  Wien, 

1887. 

11.  FURBRINGER     .    .  Le  Bull.  Med.,  Jan.  22, 1888. 

12.  ZERNER  and  LOAW  .  W.  M.  W.,  1887. 

13.  ROTHZIEGEL  and  KORAI.ZEWSKI  .  W.  M.  Bl., 

1888,  xi. 

14.  HAAS D.  A.  K.  M.,  1888,  xliii. 

15.  STAHR Th.  M.,  1898,  xii. 

16.  GOTTLIEB  and  MAGNUS  .  A.  E.  P.  P.,  xlvii.. 

xlviii. 

CAFFEINE. 

1.  RUNGE Schweigg.    Journ.    Chem. 

Phys.,  1820,  xxxi. 

2.  SCHNEIDER    .   .   .  Schicksal     des     Caffeins, 

Dorpat,  1884. 

3.  ROST A.  E.  P.  P.,  xxxvi. 

4.  ALBANESE  .   .   .   .  A.  E.  P.  P.,  xxxv. 

5.  BRILL In.  Dis.,  Marburg,  1861. 

6.  LEVEN A.  A.  P.,  1858. 

7.  BENNETT    .   .   .   .  B.  M.  J.,  1874. 

8.  LEBLOND    ....  La  Caffeine,  Paris,  1883. 

9.  RUMPF S.  Jb.,  cci.  123. 

10.  SOBIERANSKI       .    .  Cb.  P.,  X.  126. 

11.  PASCHKIS  and  PAL  .  Med.  Jahrb.  Wien,  1886. 

12.  FALK  and  STUHLMANN  .  V.  A.  P.  A.,  xii.  365. 

13.  JOHANNSEN    .   .   .In.  Dis.,  Dorpat,  1869. 

14.  MAYS T.  G.,  1885,  i.  84. 

15.  AUBERT  and  HAASE  .  A.  G.  P.,  v.  608. 

16.  MAKI In.  Dis.,  Strasburg,  1884. 

17.  FAVAL Thesis,  Lyon,  1887,  357. 

18.  BEYER A.  J.  M.  S.,  July,  1885. 

19.  BINZ A.  E.  P.  P.,  ix.  36. 

20.  REICHERT  .  .   .   .  T.  G.,  1890. 

21.  GUBLER B.  G.  T..  xci.,  523. 

22.  LANGGAARD  .   .  .  A.  E.  P.  P.,  1887,  xxii. 

23.  PHILLIPS     ....  Internal.   Med.  Congress, 

Washington,  1887. 

24.  BOCKER Beitrage  z.  Heilk.  i. 

25.  BOCKER Arch,  der  Vereins  f.  Wis- 

senschaft  Heilk.,  1854,  i. 

26.  HOPPE D.  Kl.,  1857. 

27.  BOCKER C.  R.  A.  S.,  1870,  Ixxi.  426. 

28.  LEHMANN  ....  Lehrb.  d.  Physiol.  Chem., 

Leipsic,  1842,  i. 

29.  VOIT     Untersuch.,  Munich,  1860. 

30.  Roux A.  de  P.,  1874,  i.  592. 

31.  COUTY,  GuiMARAES.and  NIOBEY  .  C.  R.  A.  S., 

xcix.  86. 

32.  PERISOT Thesis,  Paris,  1890. 

33.  REICHERT  .   .   .  .  N.  Y.  M.J.,  April,  1890. 

34.  HEERLEIN  ....  In.  Dis.,  Bonn,  1892. 

35.  HUCHARD  ....  Bull.     Soc.     M6d.    H6p., 

Paris,  1890. 

36.  ROUTH     L.  L.,  1883,  i.  680. 

y/.   CURSCHMANN     .    .  D.  Kl.,  1873,  377. 

38.  WING AN.  O.,  1003,  xii. 

39.  ANTEN A.  I.  P.  T.,  viii.  1901. 

40.  BOCK A.  E.  P.  P.,  1900,  xliii. 

41.  LOEWI A.  E.  P.  P.,  1905,  liii.  15. 

CONVALLARIA. 

1.  MARME S.  Jb.,  cxxxiv.  166. 

2.  SEE B.  A.  M.,  1882,  767. 


358 


GENERAL  REMEDIES. 


REFERENCES.— Continued. 


3.  COZE  and  SIMON  .  B.  G.  T.,  cv.  494. 

4.  OTT Arch,    of    Medicine,    Feb. 

1883. 

5.  LOWENTHAL  .  .  .  Thesis,  Wurzburg,  1885. 

6.  NATHANSON  .  .   .  L.  M.  R.,  July  15,  1887. 

7.  TROITZKY    and    BOJOJAWLEWSKY  .  Vratsch, 

1880. 

8.  DHSPLATS  ....  Journ.  des  Sciences   Med. 

de  Lille,  Oct.  1882. 

9.  STILLER W.  M.  W.,  Nov.  1882. 

10.  PEL Centralbl.  f.  Therap.,  1883. 

11.  LEYDEN D.  M.  W.,  Feb.,  1883. 

12.  JxcOBiandLuBiLiNSKi  .  Sitzungsb.d.Vereins 

f.  innere  Med.,  1883. 

13.  SILVESTRINI  ...  La  France  Med.,  Oct.  1883. 

14.  MARAGLIANA    .   .  C.  M.  W.,  1883,  43. 

15.  SANSOM L.  L.,  1886,  i. 

SPARTEINE. 

1.  H  USE  MANN    .   .   .  Pflanzenstoffe. 

2.  FICK A.  E.  P.  P.,  1887. 

3.  GLUZINSKI  ....  D.  A.  K.  M.,  1884,  xliv. 

4.  DE  RYMON     .   .   .  Thesis,  Paris,  1880. 

5.  GRIFFE Thesis,  Lyons,  1886. 


6.  CUSHNY  and  MATTHEWS  .  A.  E.  P.  P.,  1895, 

XXXV. 

7.  GuiNARDand  GELEY  .  C.  R.  S.  B.,  1894. 

8.  LABOR  DE     .   .   .   .  C.  R.  S.  B.,  1885. 

9.  GARAND Thesis,  Nancy,  1886. 

10.  MASIUS B.  A.  R.  B.,  i. 

11.  GLUZINSKI     .  .   .  Vratsch,  1887. 

12.  CERNA Amer.   Med.    Surg.    Bull., 

1894. 

13.  ROLAND Le  Poitou  Med.,  1887. 

14.  VOIT     Med.  Chron.,  April,  1887. 

15.  CLARKK A.  J.  M.  S.,  1887. 

16.  KURLOFF    ....  A.  K.  M.,  1889,  xlv. 

17.  PAWINSKI    .  .  .  .  G.  H.  M.  C.,  1888. 

18.  LEO Z.  K.  M.,  1887. 

19.  STOESSEL    ....  Centralb.  f.  Therap.,  1887. 

20.  LANNOIS S.  Jb.,  ccliii. 

21.  MUTO  and  ISHIZAKA  .  A.  E.  P.  P.,  1903. 

ADONIDIN. 

1.  CERVELLO  .  .   .   .  A.  E.  P.  P.,  xv. 

2.  HARE T.  G.,  1886,  220. 

3.  GUIRLET     ....  Thesis,  Nancy,  1888. 

4.  BUBNOW St.    Peters.    Med.  Woch., 

1879. 


FAMILY   II.— CARDIAC    DEPRESSANTS. 


THERE  are  certain  drugs  which  are  used  by  practitioners  to  decrease 
the  activity  of  the  circulation,  and  it  is  these  which  are  here  considered 
under  the  heading  of  Cardiac  Depressants.  Many,  in  fact  all  of  them, 
possess  other  powers  besides  those  which  cause  them  to  be  considered 
under  this  caption,  and  none  of  them  are  in  very  close  accord  in  these 
qualities.  There  is,  however,  a  general  resemblance  in  the  action  of  such 
as  are  derived  from  the  vegetable  kingdom,  in  that  they  are  all  depressants 
to  the  motor  nervous  system  and  yet  all  produce  convulsions.  H.  C. 
Wood 1  has  made  an  especial  experimental  study  of  these  convulsions, 
and  has  found  that  they  are  cerebral  and  not  spinal,  because  they  do 
not  occur  in  any  part  of  the  body  separated  by  section  of  the  cord  from 
cerebral  influence.  Further,  they  are  probably  due  to  disturbance  of  the 
circulation  at  the  base  of  the  brain,  for  the  following  reasons,  the  truth 
of  each  of  which  has  been  experimentally  determined  :  first,  lessening  of 
the  circulation  at  the  base  of  the  brain  will  cause  convulsions  ;  secondly, 
the  convulsions  produced  by  the  cardiac  depressants  do  not  occur  until 
the  arterial  pressure  is  reduced  about  one-half ;  thirdly,  if  the  disturbance 
of  the  cerebral  circulation  be  artificially  increased  by  tying  the  carotids 
previous  to  poisoning,  or  in  any  other  way,  the  convulsions  come  on 
sooner  and  are  more  violent  ;  fourthly,  in  some  animals  the  convulsions 
caused  by  arresting  circulation  at  the  base  of  the  brain  are  feeble  and  ill- 
defined,  while  in  others  they  are  violent,  and  in  species  of  the  first  order 
cardiac  depressants  produce  but  slight  convulsions,  while  in  species  of  the 
second  order  they  cause  violent  convulsions. 

The  indications  for  the  use  of  a  cardiac  depressant  may  be  said  to  be 
increased  arterial  excitement,  sthenic  fevers,  and  severe  local  inflamma- 
tions. In  order  that  a  rational  selection  of  the  various  drugs  may  be 
made  for  any  individual  case,  it  is  necessary  to  study  how,  in  these 
various  conditions,  relief  is  afforded  by  an  arterial  sedative.  When 
there  is  arterial  excitement  from  irritation  or  excitement  of  the  heart, 
the  mode  of  relief  is  too  obvious  to  need  discussion.  It  is  plain  that 
in  such  a  case  a  drug  should  be  selected  which  simply  depresses  the 
heart's  action  and  does  nothing  more.  When  there  is  severe  inflam- 
mation, such  as  pneumonia,  with  high  arterial  tension,  the  effect  desired 
is  a  lessening  of  the  flow  of  blood  to  the  part.  A  simple  cardiac  de- 
pressant may  do  this  by  lowering  the  force  of  the  circulation,  but  a  car- 
diac vaso-motor  depressant  is  far  more  powerful.  The  blood-vessels  of 
the  inflamed  part  are  already  dilated,  and  consequently  attract  blood,  as 
it  were,  to  the  part.  If  the  remedy  dilates  all  the  blood-vessels,  this 

359 


360  GENERAL  REiMEDIES. 

local  attraction  ceases,  and  blood  is  diverted  from  the  inflamed  tissue. 
It  would  appear  from  the  experiments  of  Ludwig,  Schiff,  and  others* 
that  the  blood-vessels  of  the  body,  after  complete  dilatation,  are  able  to 
hold  twice  their  normal  amount  of  blood,  and  Golz  (quoted  by  Fother- 
gill3)  found  that  the  intestinal  vessels  by  themselves  were  able  to  contain 
all  the  blood  of  the  body.  These  facts  show  how  by  means  of  an  arterial 
sedative,  which  paralyzes  the  vaso-motor  centres,  "we  can  bleed  a  man 
into  his  own  blood-vessels,"  or,  in  other  words,  get  much  of  the  effect  of 
a  venesection  by  drawing  blood  from  the  diseased  part. 

ANTIMONY. 

ANTIMONII    OXIDUM— ANTIMONY   OXIDE. 

A  grayish-white  powder,  almost  insoluble  in  water.  Its  solution  in 
the  stomach  is  dependent  upon  the  acid  there  present,  and  it  should  not 
be  used  internally, — although  it  is  capable  of  producing  all  the  effects  of 
tartar  emetic — and  is  no  longer  recognized  by  the  U.  S.  Pharmacopoeia. 
ANTIMONII  SULPHIDUM,  ANTIMONII  SULPHIDUM  PURIFICATUM,  and 
ANTIMONIUM  SULPHURATUM,  are  still  more  uncertain  preparations  which 
were  very  properly  dropped  at  the  8th  revision  U.  S.  Pharmacopoeia. 

ANTIMONII   ET   POTASSII  TARTRAS— ANTIMONY  AND  POTASSIUM 

TARTRATE.     U.S. 

TARTAR  EMETIC  occurs  in  the  form  of  a  white  powder,  the  result 
of  the  pulverization  of  transparent,  colorless,  slightly  efflorescent  crystals, 
which  are  most  commonly  rhombic  octahedrons.  Its  taste  is  at  first 
very  slight,  but  after  a  time  styptic  and  acrid.  In  some  persons  it  blis- 
ters the  tongue  and  lips  after  a  few  moments  of  contact.  Tartar  emetic 
is  insoluble  in  absolute  but  soluble  in  dilute  alcohol,  soluble  in  from  two 
to  three  parts  of  boiling  water,  and  in  seventeen  parts  of  water  at  59°  F. 
It  is  incompatible  with  alkalies  and  with  acids,  including  tannic  acid  and 
substances  containing  it. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Locally  applied,  tartar 
emetic  is  an  irritant,  acting  upon  some  very  delicate  and  susceptible 
skins  in  a  very  short  time.  In  most  instances,  however,  its  continuous 
application  for  several  days  is  necessary  to  produce  any  effect.  At  first 
there  is  simply  a  redness,  accompanied  by  some  burning  pain  and  the 
eruption  of  small  papules,  which  shortly  become  converted  into  vesicles 
and  then  into  pustules.  These  are  irregular  in  shape  and  size,  varying 
from  one-eighth  of  an  inch  to  an  inch  and  a  half  in  diameter,  and  are 
very  painful.  Sometimes  these  pustules  give  rise  to  small  sloughs,  but 
generally,  if  the  application  be  withdrawn,  they  simply  give  origin  to 
superficial  ulcers,  which  readily  heal. 

Absorption  and  Elimination. — Tartar  emetic  is  very  rapidly  absorbed 
in  the  gastro-intestinal  tract,  and  elimination  commences  almost  at  once. 
The  minute  dose  probably  escapes  from  the  system  altogether  through  the 


CARDIAC    DEPRESSANTS.  361 

kidneys  but  the  toxic  dose  is  certainly  thrown  off  with  the  secretions  from 
the  whole  length  of  the  gastro-intestinal  tract,  and  probably  also  escapes 
with  the  saliva.  Elimination  is,  however,  not  complete,  so  that  in  cases 
of  fatal  poisoning  antimony  may  be  found  in  the  various  tissues  of  the  body. 

Masoin 15  believes  that  the  fixation  of  the  antimony  in  the  tissue  begins  almost  at 
once,  because  he  found  that  if  he  gave  to  the  rabbit  the  minimum  fatal  dose  of  tar- 
tar emetic,  then  bled  and  practised  transfusion  either  with  blood  from  another 
rabbit  or  with  normal  salt  solution,  the  animal  died  as  quickly  as  did  the  animal 
left  to  the  action  of  the  poison  ;  although  when  five  or  six  times  the  minimum  fatal 
dose  was  given  bleeding  and  transfusion  greatly  protracted  life.  Moreover,  blood 
drawn  from  the  animal  poisoned  with  the  minimum  fatal  dose  was  only  slightly  toxic. 

General  Action. — The  only  symptoms  which  are  induced  by  small 
therapeutic  doses  (one-twelfth  of  a  grain)  of  tartar  emetic  when  exhibited 
for  a  short  time  are  a  scarcely  perceptible  diminution  of  the  force  of  the 
pulse  and  an  increase  of  the  perspiration.  By  somewhat  larger  amounts 
of  the  drug  nausea  is  induced,  accompanied  in  a  more  decided  degree 
by  the  phenomena  just  mentioned.  After  large  doses,  prolonged  nausea, 
violent  vomiting  and  retching,  with  marked  reduction  of  the  force  of  the 
pulse,  great  muscular  relaxation,  and  a  feeling  of  faintness,  occur.  At 
the  same  time  the  saliva  is  generally  increased  in  amount  and  the  skin  is 
bedewed  with  sweat. 

After  poisonous  doses  all  these  symptoms  are  intensified.  The  vomit- 
ing is  violent,  repeated,  continuously  re-excited  by  the  slightest  provoca- 
tion, and  is  accompanied  by  burning  in  the  oesophagus  and  stomach  and 
by  colicky  pains  in  the  abdomen.  The  matters  vomited  are  first  mucus, 
then  mucus  with  bile,  and  finally,  in  some  cases,  blood.  With  the  gas- 
tric disturbance  occurs  violent  and  frequent  serous  purging,  the  discharges 
resembling  those  of  cholera,  but  becoming  in  some  cases  towards  the  last 
bloody.  Cramps  may  occur  in  the  extremities,  and,  in  conjunction  with 
the  serous  purging,  have  caused  the  antimonial  poisoning  to  be  mistaken 
for  cholera.  The  exhaustion  is  extreme,  and  deepens  into  collapse,  with 
thready  or  imperceptible  pulse,  pinched,  livid  countenance,  suppressed 
voice,  profuse  cold  sweats,  lowered  temperature,  and  at  last  death  from 
asthenia,  generally  preceded  by  stupor  or  convulsions  :  indeed,  Taylor 
reports  cases  in  which  wild  delirium  was  present  some  hours  before  death. 
The  urine  *  in  mild  cases  is  increased  in  quantity,  as  it  is  also  in  the  be- 
ginning even  in  fatal  cases,  but  in  such  towards  the  close  it  is  generally 
scanty  and  bloody,  and  even  suppressed.  Upon  the  lower  mammals 
tartar  emetic  acts  precisely  as  it  does  on  man. 

*  What  is  said  in  the  text  is,  we  think,  correct,  although  authorities  differ  on  this 
point.  Trousseau  (  Traite  de  Therapeutique,  4th  ed.,  i.  619)  affirms  that  it  is  suppressed  ; 
Husemann,  that  it  never  is  suppressed  ( Toxicologie,  854) ;  Tardieu,  that  it  is  scanty. 
For  a  case  in  which  it  was  suppressed,  see  Taylor's  Medical  Jurisprudence,  London, 
l873.  3°9-  C.  Gathgens  (Centralbl.f.  Med.  Wiss.,  1870,  321)  found,  in  some  incomplete 
experiments,  an  increase  of  the  elimination  of  urea  after  repeated  non-toxic  doses  of 
antimony. 


362  GENERAL  REMEDIES. 

Circulation. — In  man  and  in  all  mammals  any  dose  of  tartar  emetic 
which  is  sufficient  to  affect  the  circulation  produces  a  steady  fall  of  the 
arterial  pressure,  with  a  pulse-rate  which  may  be  at  first  slowed  but  soon 
becomes  more  rapid  than  the  normal. 

In  the  lower  animals  all  doses  of  antimony  sufficient  to  cause  any  apparent 
effect  progressively  lower  the  arterial  pressure  ;  the  pulse  is  sometimes  at  first  tem- 
porarily accelerated,  but  usually  the  slowing  of  the  pulse  occurs  from  the  beginning  of 
the  poisoning.  During  this  period  of  slow  pulse  the  diastolic  pauses  are  extremely 
long  and  the  pulse-waves  greatly  augmented,  it  may  be  to  five  times  their  original 
size.  After  a  time  the  pulse  usually  becomes  very  rapid,  the  pulse-waves  very  small, 
the  arterial  pressure  almost  extinguished,  and  in  a  few  minutes  diastolic  arrest 
occurs  (Ackermann,1  Ernst  Sentz2).  In  the  poisoned  frog  the  cardiac  contrac- 
tions are  from  the  beginning  lessened  in  frequency  and  force,  then  become  more 
rapid  but  extremely  irregular,  with  the  auricles  pulsating  more  frequently  than  the 
ventricles  (Radziejewski,8  Ackermann,  Nobiling*).  The  peripheral  vagi  are  para- 
lyzed so  that  the  diastolic  arrest  is  not  inhibitory  (Radziejewski).  Antimony  para- 
lyzes the  isolated  frog's  heart,  destroying  the  irritability  of  the  muscle  (Ackermann) ; 
digitalis  is  stated  to  produce  immediate  restoration  of  function  (I.  Soloweitschyk5). 

Antimony  is  certainly  a  direct  cardiac  depressant  and  paralyzant,  but 
the  assertion  of  Soloweitschyk  that  galvanization  of  the  vaso-motor  centre 
does  not  elevate  the  arterial  pressure  whilst  the  heart  is  still  active,  taken 
together  with  the  fact  that  the  arterial  pressure  falls  whilst  the  heart  is 
apparently  putting  forth  its  normal  force,  indicates  that  the  poison  also 
depresses  either  centrically  or  peripherally  the  blood-vessel  system. 

Nervous  System. — The  occurrence  in  man  of  anaesthesia  during  anti- 
monial  poisoning  has  been  overlooked,  but  has  been  a  marked  feature  in 
experimental  poisonings.  According  to  Radziejewski,  the  thermic  sense 
is  first  paralyzed  and  later  the  tactile  power.  Radziejewski  and  Soloweits- 
chyk have  found  that  the  depression  of  reflex  activity  occurs  after,  as 
before,  section  of  the  cord,  and  is  therefore  not  due  to  stimulation  of  the 
Setschenow  inhibitory  centre  ;  also  that  it  is  not  prevented  by  tying  an 
artery  and  cutting  off  access  of  the  poison  to  the  nerve,  and  is  therefore 
not  peripheral.  It  consequently  must  be  spinal ;  and,  as  both  observers 
noted  that  in  the  frog  and  the  rabbit  voluntary  movements  persist  after 
the  total  abolition  of  sensibility  and  reflex  activity,  antimony  must  be  a 
paralyzant  of  the  receptive  centres  or  sensory  tract  of  the  spinal  cord.  The 
motor  cord  probably  shares  to  a  slight  extent  in  the  depressing  influence. 
The  motor  nerves  and  muscles  are  said  to  retain  their  functional  power. 

Temperature. — The  influence  of  antimony  upon  the  temperature  ap- 
pears not  to  be  very  marked  when  the  drug  is  exhibited  in  ordinary 
therapeutic  doses.  Ackermann  affirms  that,  after  doses  severe  enough  to 
induce  violent  vomiting,  the  centric  temperature  is  not  lowered,  although 
that  of  the  extremities  may  fall  as  much  as  3.5°  C.  After  poisonous 
doses  of  antimony  the  decrease  of  animal  heat  is  very  perceptible.* 

*  Ackermann  found  that  a  fall  of  only  1.6°  C.  occurred  in  rabbits  killed  in  an  hour, 
but  in  those  that  lived  five  hours  the  depression  amounted  to  6.6°  C. 


CARDIAC   DEPRESSANTS.  363 

Abdominal  Organs. — Tartar  emetic  acts  as  an  irritant  upon  the  whole 
alimentary  mucous  membrane.  The  serous  discharges  from  the  stomach 
and  from  the  bowels  may  be  to  a  certain  degree  due  to  the  local  irritant 
influence  of  the  poison,  but  probably  to  a  much  larger  degree  are  the 
outcome  of  an  attempt  to  eliminate  the  drug  circulating  in  the  blood. 

Brinton  proved  that  when  tartar  emetic  was  injected  into  the  vein  of  an  animal 
it  was  very  freely  and  rapidly  eliminated  by  the  stomach.  B.  W.  Richardson  6  has  cor- 
roborated this,  and  has  also  found  that  a  similar  elimination  follows  the  inhalation 
of  antimonietted  hydrogen.  Radziejewski's  theory  that  the  emesis  is  due  solely  to  a 
local  action  of  the  poison  is  completely  disproved  by  the  experiments  of  Magendie 
(confirmed  by  Brinton T),  in  which  vomiting  was  produced  by  tartar  emetic  after 
the  stomach  had  been  removed  and  a  pig's  bladder  substituted.  The  vomiting 
caused  by  tartar  emetic  must  therefore  be,  at  least  in  part,  of  centric  origin,  but 
Mosso  8  has  proved  that  the  local  action  of  the  drug  also  plays  an  important  rdle  in 
the  production  of  vomiting  ;  finding  that  when  the  tartar  emetic  is  given  by  the  mouth, 
vomiting  is  caused  by  smaller  quantities  and  more  promptly  than  when  the  poison 
is  injected  into  the  veins. 

Respiratory  Organs. — The  respiration  in  poisoning  by  antimony  is 
very  irregular,  with  all  sorts  of  variations  in  the  rhythm  of  the  act,  and 
is  probably  centrally  depressed. 

In  the  advanced  stages  the  pauses  are  often  very  long,  and  the  inspiration  and 
expiration  so  forced  and  prolonged  that  very  generally,  in  animals  at  least,  mar- 
ginal emphysema  and  subpleural  ecchymoses  are  found  after  death.  The  origin 
of  the  respiratory  trouble  is  probably  somewhat  complex,  the  chief  factor  being 
the  direct  influence  of  the  drug  upon  the  respiratory  nerve-centres,  and  minor  causes 
the  intense  venous  congestion  due  to  the  failure  of  the  circulation  and  the  alteration 
of  the  blood  itself. 

Upon  the  mucous  membrane  of  the  lungs  antimony  acts  directly  or 
indirectly,  even  in  moderate  doses,  as  is  shown  by  clinical  experience  and 
by  the  experiments  of  Mayerhofer.9 

SUMIVLABY. — Locally,  tartar  emetic  is  a  violent  irritant,  -which  is 
rapidly  absorbed  and  rapidly  eliminated  through  the  kidneys,  and  also, 
when  the  dose  has  been  large,  through  the  mucous  membranes  of  the 
whole  gastro-intestinal  tract,  causing  during  the  process  of  elimination 
violent  inflammation  and  it  may  be  destruction  of  the  eliminating  tis- 
sues. It  is  a  powerful  depressant  to  the  circulation,  acting  directly 
upon  the  heart-muscle  or  its  contained  ganglia,  and  also  widening  out 
blood-paths  by  paralyzing  the  vessels,  whether  centrically  or  periphe- 
rally is  not  known.  By  the  toxic  dose  the  peripheral  vagi  are  depressed 
and  finally  paralyzed.  The  vomiting  produced  by  tartar  emetic  is  in 
part  due  to  the  local  action  of  the  drug  upon  the  stomach,  but  is  chiefly 
centric.  The  largest  therapeutic  dose  has  no  perceptible  direct  action 
upon  the  nervous  system,  but  the  toxic  dose  depresses  the  respiratory 
centres,  the  receptive  or  sensory  centres  of  the  spinal  cord,  and  finally 
the  motor  cord, — the  nerves  and  the  voluntary  muscles  retaining  their 
functional  power  Tartar  emetic  kills  by  producing  exhaustion  and  by 
paralyzing  the  respiratory  centres  and  also  the  heart. 


364  GENERAL  REMEDIES. 

THERAPEUTICS. — There  are  three  indications  to  meet  which  tartai 
emetic  is  constantly  employed.  The  first  of  these  it  fulfils  by  virtue  of  its 
powers  as  an  emetic.  The  discussion  of  this  may  be  found  in  the  chapter 
upon  Emetics. 

The  second  purpose  for  which  antimony  is  used  is  to  depress  arterial 
excitement.  It  is  chiefly  in  inflammation  that  tartar  emetic  is  used  as  an 
arterial  sedative.  In  combination  with  more  decided  diaphoretics  it  is 
constantly  employed  by  some  surgeons  in  gonorrhcea  and  in  various  sthenic 
inflammatory  affections.  In  pneumonia  it  has  been  very  largely  used, 
forming  an  essential  portion  of  the  old  so-called  contra-stimulant  plan 
of  treating  that  disease.  According  to  the  method  of  Rasori,  four  or 
five  grains  a  day  were  at  first  given,  but  rapidly  increased  to  twenty-four 
or  even  thirty  grains  daily.  Although  by  the  aid  of  opiates  and  careful 
dilution  a  species  of  tolerance  was  often  obtained  for  these  heroic  doses, 
the  method  has  very  properly  been  abandoned  by  modern  therapeutists. 
Whenever  tartar  emetic  is  given  in  such  quantities  as  markedly  to  de- 
press the  circulation  by  the  vomiting  and  purging  which  it  causes,  it  pro- 
duces in  the  patient  exhaustion  as  well  as  depression.  Further,  by  the 
continuance  of  its  local  influence  upon  the  intestinal  tract  after  the  period 
of  depression,  it  interferes  with  the  digestion  of  food  and  consequently 
with  the  regaining  of  power.  On  the  contrary,  neither  aconite  nor  vera- 
trum  directly  exhausts,  though  they  powerfully  depress.  They  are, 
therefore,  always  preferable  to  tartar  emetic  when  in  a  pneumonia  or  other 
disease  it  is  desired  to  produce  a  temporary  pronounced  depression  of  the 
circulation.  In  fact,  tartar  emetic  should  never  be  employed  as  an  active 
depressant  of  the  circulation. 

Owing  to  its  action  upon  the  mucous  membrane  of  the  bronchial  tubes, 
in  the  first  stages  of  bronchitis  tartar  emetic  is  a  valuable  remedy.  After 
free  secretion  has  been  established,  other  expectorants  are,  we  think,  of 
more  service.  It  should  be  used  only  in  sthenic  cases,  and  never,  unless 
in  the  most  minute  dose,  in  children  or  the  aged. 

As  a  counter-irritant,  tartar  emetic  is  used  only  when  it  is  desired  to 
produce  a  slow,  persistent,  and  at  the  same  time  very  decided  impres- 
sion. For  further  discussion  of  its  application  to  disease,  see  the  chapter 
on  Rubefacients. 

TOXICOLOGY. — The  symptoms  ordinarily  produced  by  poisonous 
doses  of  antimony  have  been  sufficiently  described.  There  is,  however, 
according  to  authors,  a  form  of  antimonial  poisoning  in  which  neither 
vomiting  nor  purging  *  occurs,  the  symptoms  being  simply  intense  pros- 
tration, cold  clammy  sweat,  a  sense  of  oppression  in  the  chest,  with  the 
respiration  at  first  increased,  then  diminished  in  frequency  and  embar- 
rassed ;  a  rapid  feeble  pulse,  after  a  time  becoming  slow,  intermittent, 
and  irregular  ;  delirium,  unconsciousness,  tremblings,  and  clonic  and 

*  Huscmann  states  this.  Although  vomiting  is  absent  in  these  cases,  purging  is  gen- 
erally present.  We  do  not  remember  to  have  seen  the  report  of  a  case  in  which  it  was 
absent. 


CARDIAC   DEPRESSANTS.  365 

tonic  convulsions  (Husemann10).  Tardieu  states  that  in  some  cases  of 
tartar  emetic  poisoning  a  rash  exactly  resembling  that  produced  by  the 
external  application  of  the  drug  has  appeared  all  over  the  body  on  the 
fourth  or  fifth  day. 

The  symptoms  of  antimonial-poisoning  so  closely  resemble  those  of 
arsenical-poisoning  and  of  choleraic-diarrhoea,  that  when  there  is  no  dis- 
tinct history,  certainty  of  diagnosis  can  only  be  reached  by  an  analysis  of 
the  excretions.  In  any  suspected  case  of  poisoning  it  is  the  duty  of  the 
practitioner  to  save  the  urine  for  chemical  examination. 

The  lesions  of  gastro-enteritis  which  are  usually  found  after  death 
from  tartar  emetic  are  sometimes  not  present.*  The  venous  system  is 
generally  very  much  engorged,  and  the  viscera  are  intensely  congested. 
Magendie  asserted  that  in  animals  poisoned  by  tartar  emetic  the  lungs  are 
always  full  of  portions  apparently  hepatized  ;  but  Ackermann,  in  twenty 
experiments,  found  only  some  marginal  emphysema  and  subpleural  ecchy- 
moses,  with,  in  one  or  two  cases,  spots  of  atelectasis  in  the  lungs.  The 
assertion  of  Magendie,  therefore,  is  too  sweeping  ;  but  it  is  true  that,  in 
a  large  proportion  of  fatal  cases  of  antimonial  poisoning,  emphysema, 
pulmonary  apoplexy,  atelectasis,  or  other  structural  lesions  of  the  lungs 
exist.  The  blood  usually  coagulates  imperfectly. 

Salkowsky,11  of  Moscow,  has  found  that  when  animals  are  fed  upon 
antimonic  acid  (one- half  to  one  gramme  daily)  or  other  preparations  of 
the  metal  for  from  fourteen  to  nineteen  days,  the  liver,  kidneys,  and 
even  the  heart  undergo  fatty  degeneration  ;  also  that  there  is  a  lessen- 
ing of  the  amount  of  glycogen  in  the  liver,  and  in  some  cases  even  a  total 
disappearance  of  it.  This  has  been  confirmed  by  Grohe  and  M osier,  who 
state  that  in  the  duchy  of  Brunswick  the  peasantry  give  to  the  geese, 
when  producing  the  famous  fatty  livers,  a  certain  quantity  of  the  white 
antimony  oxide  every  day. 

The  minimum  fatal  dose  of  tartar  emetic  is  not  known.  Three- 
quarters  of  a  grain  in  a  child,  and  two  grains  in  an  adult,  have  proved 
fatal,  but  in  the  latter  case  extrinsic  circumstances  favored  the  result 
(Taylor,12  an  analysis  of  thirty-seven  fatal  cases);  two  hundred  grains 
have  been  recovered  from  ; 13  also  one  hundred  and  seventy  grains. u 

The  treatment  of  antimonial  poisoning  consists  in  washing  out  the 
alimentary  canal  with  large  draughts  of  tannic  acid, — the  best  known 
antidote, — in  the  free  administration  of  opium  by  the  mouth  or  rectum, 
or  hypodermically  if  it  cannot  be  retained,  the  hypodermic  injections  of 
strychnine  and  digitalis  if  the  circulation  fails,  and  the  maintenance  of 
the  bodily  temperature  by  external  application  of  heat. 

Chronic  Poisoning. — The  symptoms  following  the  criminal  repeated 
administration  of  small  toxic  doses  of  tartar  emetic  at  intervals  are  nausea, 
mucous  and  bilious  vomiting,  watery  purging,  often  followed  by  constipation, 
small  frequent  pulse,  and  asthenia,  deepening  into  death  from  exhaustion. 

*  For  cases,  see  Archives  Gtn.,  September,  1865. 


366  GENERAL  REMEDIES. 

ADMINISTRATION. — The  sudorific  dose  of  tartar  emetic  is  one-twelfth 
of  a  grain  (0.0054  Gm.),  the  emetic  dose  one-half  to  one  grain  (0.032- 
0.065  Gm.),  repeated  every  twenty  minutes  as  necessary.  Antimonial 
Wine  (ViNUM  ANTIMONII,  U.  S. ).  about  two  grains  to  one  fluidounce  ; 
full  emetic  dose  half  a  fluidounce  (15  C.c.).  An  ointment  (twenty  per 
cent. )  has  been  used  as  a  pustulating  counter-irritant.  A  small  quantity 
is  spread  upon  a  linen  rag  and  laid  upon  the  skin,  or  a  little  of  it  may  be 
well  rubbed  in  twice  a  day.  The  effects  are  severe  and  persistent. 


VERATRUM.     U.  S. 

The  U.  S.  Pharmacopoeia  formerly  recognized  under  the  name  of 
Veratrum  viride  the  rhizomes  and  roots  of  that  North  American  plant. 
Very  unfortunately,  at  the  recent  Eighth  Revision  of  the  Pharmacopoeia, 
Veratrum  viride  was  dropped  as  an  official  title  and  Veratrum  defined  as 
the  rhizomes  of  Veratrum  viride  and  Veratrum  album.  These  two 
plants,  one  a  native  of  North  America,  the  other  of  Europe,  are  so 
closely  allied  that  by  many  botanists  they  have  been  thought  to  be  iden- 
tical, though  at  present  they  are  by  most  authorities  believed  to  be  dis- 
tinct. The  rhizomes  are  very  similiar  in  appearance  and  probably  con- 
tain the  same  alkaloids  and  resemble  one  another  very  closely  in  their 
physiological  action  (See  H.  C.  Wood  and  H.  C.  Wood  Jr.1),  but  simi- 
larity is  not  identity,  and  both  the  chemical  and  toxicological  evidence 
indicate  that  the  European  plant  is  much  stronger,  than  is  the  North 
American,  and  that  the  two  rhizomes  probably  differ  essentially  in  the 
proportionate  amounts  of  the  various  alkaloids  contained  in  them.  A 
number  of  cases  of  fatal  poisoning  by  Veratrum  album  have  been 
recorded  ;  we  know  of  none  in  the  healthful  adult  from  Veratrum  viride. 
In  the  poisoning  with  Veratrum  album,  violent  abdominal  pain  and 
diarrhoea  are  usually  present ;  they  are  rare  in  poisoning  with  Veratrum 
viride.  In  our  opinion,  the  medical  practitioner  who  wishes  to  produce 
a  profound  influence  with  Veratrum  viride  should  always  order  and  see 
that  he  gets,  not  the  veratrum  of  the  U.  S.  P.  but  veratrum  viride. 

The  latter  researches  seem  to  show  that  there  are  in  Veratrum  viride 
six  alkaloids  instead  of  two,  as  was  at  one  time  believed.  (See  U.  S. 
Dispensatory. )  Of  these  alkaloids  the  most  important  are  rubijervine 
(the  veratroidine  of  Charles  Bullock,  and  of  the  text  of  this  book),  and 
jervine ;  whilst  pseudojervine,  cevadine,  veratrine,  and  veratralbine  are 
present  only  in  very  minute  quantities.  The  same  alkaloids  are  probably 
present  in  Veratrum  album,  but  we  repeat,  there  is  no  proof  that  they 
are  present  in  the  same  proportions  as  they  are  in  Veratrum  viride. 

Local  Action. — Veratrum  viride  is  not  actively  irritant,  although  there 
is  reason  for  believing  that  the  vomiting  which  it  causes  is  partly  due  to 
some  local  influence  exerted  by  it  upon  the  stomach.  It  yields  its  active 
principle  very  rapidly  to  absorption  ;  its  effects  become  apparent  in  fifteen 
to  twenty-five  minutes  after  its  ingestion.  Concerning  its  elimination  we 


CARDIAC    DEPRESSANTS.  367 

have  no  practical  knowledge,  but  its  active  principle  probably  escapes 
through  the  urine. 

General  Action. — The  only  effect  perceptible  in  man  after  the  small 
physiological  dose  of  veratrum  viride  is  a  reduction  of  the  force  of  the 
pulse.  If  the  dose  has  been  a  little  larger  the  pulse  frequency  also 
falls  very  markedly,  it  may  be  to  40  or  even  30  per  minute.  The  vol- 
ume of  the  pulse  rises,  though  the  force  of  it  is  very  slight.  The  final 
reduction  of  the  pulse-rate  is  accompanied  by  nausea,  and  at  .last  by 
vomiting,  which  becomes  after  a  very  large  dose  exceedingly  severe.  By 
exercise  this  slow,  large,  soft  pulse  may  be  converted  into  a  rapid,  very 
feeble  and  small  pulse.  Under  any  circumstances  the  rapid  pulse  de- 
velops sooner  or  later  if  the  dose  has  been  sufficient,  and  is  accompanied 
by  intense  muscular  weakness  and  great  sweating.  Finally,  there  are  a 
running,  almost  imperceptible  pulse  ;  a  cold,  clammy  skin  ;  intense 
nausea,  and  incessant  attempts  at  vomiting,  or  retching,  or  hiccough  ; 
absolute  muscular  prostration  ;  faintness  ;  vertigo  ;  loss  of  vision  ;  and 
semi-unconsciousness.  Various  observers  also  speak  of  an  excruciating 
praecordial  pain  ;  but  this  we  have  not  seen.  The  intestines  are  usually 
not  disturbed,  but  severe  purging  has  been  noted. 

In  1870  H.  C.  Wood1  made  an  elaborate  study  of  the  alkaloids  jer- 
vine  and  veratroidine  (rubijervine)  supplied  to  him  by  Charles  Bullock, 
with  results  which  are  here  epitomized. 

In  the  dog  and  rabbit  jervine  caused  sluggishness,  with  progressive  muscular 
weakness  and  diminution  of  the  reflexes  ;  with,  after  a  time,  violent  general  tremors 
ending  in  convulsions  in  which,  although  the  movements  were  violent,  there  was 
evident  loss  of  power.  The  pupils  were  not  affected ;  there  was  no  purging  or 
vomiting,  though  always  profuse  salivation.  Locally,  jervine  was  not  irritant.  Con- 
sciousness was  preserved  almost  to  the  last,  and  death  occurred  from  asphyxia. 
Physiological  studies  showed  that  the  convulsions  were  of  cerebral  origin,  but  were 
probably  due  to  disturbances  of  circulation  in  the  brain,  the  brain  not  being  other- 
wise affected  ;  also  that  the  loss  of  muscular  power  was  due  to  spinal  depression, 
the  function  of  the  peripheral  nerves  and  the  muscles  not  being  interfered  with. 

Upon  the  respiratory  centres  jervine  acted  as  a  direct  depressant,  but  its  influ- 
ence upon  the  circulation  was  not  at  all  subordinate  to  its  action  upon  the  respira- 
tion, and  when  final  arrest  of  respiration  occurred  the  circulatory  forces  were 
almost  abolished.  The  circulatory  phenomena  were  primary  slowing  of  the  pulse, 
with  later  rapid  pulse,  and  a  progressive  falling  of  the  arterial  pressure  from  the 
beginning  to  the  end.  The  slowing  of  the  pulse  was  not  due  to  any  effect  on  the 
pneumogastric  nerves,  but  to  a  direct  influence  upon  the  heart-muscle  or  its  ganglia, 
which  is  depressed  by  any  dose  of  the  poison.  As,  however,  neither  asphyxia  nor 
galvanization  of  a  sensory  nerve  produces  rise  of  pressure  in  the  poisoned  animal, 
it  is  evident  that  jervine  depresses  the  vaso-motor  centres. 

The  physiological  action  of  jervine  may  be  summed  up  as  that  of  a 
powerful  depressant  of  the  heart  and  of  the  vaso-motor  centres,  which 
acts  also  upon  the  motor  side  of  the  spinal  cord  and  upon  the  respiratory 
centre,  but  has  little  other  influence  upon  the  organism. 


368  GENERAL  REMEDIES. 

Veratroidine  was  found  to  be  more  irritant  than  jervine,  producing  usually 
vomiting  and  sometimes  purging,  but  not  causing  such  severe  convulsions  as  did 
jervine,  death  taking  place  from  central  asphyxia.  In  its  relations  with  the  cere- 
brum, the  spinal  cord,  the  peripheral  nerves,  and  the  muscles  veratroidine  prac- 
tically acted  like  jervine.  The  circulatory  action  of  veratroidine  was  entirely 
subordinate  to  its  influence  on  the  respiration,  so  that  when  given  in  toxic  dose 
hypodermically  it  caused  an  enormous  rise  of  the  arterial  pressure,  due  to  the 
rapidly  induced  centric  asphyxia,  as  was  shown  by  the  fact  that  it  did  not  occur 
when  artificial  respiration  was  maintained.  After  section  of  the  par  vagum,  vera- 
troidine Was  powerless  to  reduce  the  pulse-rate,  and  division  of  the  par  vagum  in  the 
poisoned  animal  was  followed  by  an  enormous  rise  in  the  pulse-rate.  Further,  it 
was  found  possible  to  cause  by  the  intravenous  administration  of  a  certain  dose  of 
veratroidine,  artificial  respiration  being  maintained,  a  diastolic  arrest  of  the  heart's 
action,  which  was  at  once  relieved  by  division  of  the  par  vagum  or  by  a  second 
injection  of  the  poison  ;  so  that  an  animal  apparently  dead  could  be  restored  to 
life  by  vagal  section  or  by  giving  more  of  the  poison.  As  it  was  proved  that  the 
large  dose  of  veratroidine  paralyzes  the  peripheral  vagi,  it  is  evident  that  the  dia- 
stolic arrest  just  spoken  of  was  due  to  excessive  cardiac  inhibition,  and  that  its  re- 
moval by  section  with  the  knife,  or  with  the  drug,  allowed  the  heart  to  go  on. 

During  the  period  of  low  pressure,  galvanization  of  the  sensitive  nerve,  or  as- 
phyxia, produced  an  immediate  rise  in  the  arterial  pressure,  conclusive  proof  that 
the  vaso-motor  centres  were  not  affected. 

These  effects  upon  the  circulation  were  obtained  only  when  artificial  respira- 
tion was  maintained,  the  effect  of  the  drug  upon  the  respiratory  centre  being  so 
intense  that  when  the  animal  is  left  to  itself  death  occurs  before  any  very  direct 
influence  has  been  exerted  upon  the  circulation. 

Veratroidine  is,  therefore,  a  powerful  respiratory  poison,  lessening  at 
first  the  frequency  of  the  cardiac  beat  by  stimulating  the  pneumogastrics, 
but  soon  losing  all  power  over  the  heart,  owing  to  the  powerful  influences 
of  the  asphyxia  produced  by  it. 

The  action  of  veratrum  viride  is  the  result  of  the  combined  influence 
of  its  alkaloids,  and  as  the  relative  proportions  of  these  alkaloids  differ  in 
different  rhizomes,  so  in  the  finer  details  of  its  physiological  action  one 
specimen  of  veratrum  viride  differs  from  another.  For  all  practical  pur- 
poses, however,  its  influence  is  uniform,  and  may  be  summed  up  as 
follows  : 

SUMMARY. — Veratrum  viride  has  no  distinct  local  action,  yields 
readily  its  active  principles  to  absorption  and  probably  to  elimina- 
tion, though  concerning  its  fate  in  the  system  we  have  no  definite 
information.  The  free  sweating  which  accompanies  its  marked  action 
may  be  simply  the  result  of  a  profound  arterial  depression,  there  being 
no  proof  that  the  drug  exerts  a  specific  influence  upon  the  glands  of  the 
skin.  Similarly  the  excessive  secretion  of  bile  which  it  sometimes  in- 
duces may  be  a  secondary  result  due  to  the  severe  vomiting. 

By  the  depressing  action  of  jervine  upon  the  heart-muscle  and  upon 
the  vaso-motor  centres,  veratrum  viride  lowers  the  arterial  pressure,  in 
the  beginning  slowing  the  pulse  by  a  direct  influence  of  jervine  upon  the 
heart-muscle,  and  by  the  stimulating  influence  of  veratroidine  upon  the 
pneumogastric  nerve,  but  later  increasing  the  rapidity  of  the  pulse  by 
paralyzing  the  pneumogastric  nerve  (veratroidine),  and  probably  also 
by  some  action  upon  the  heart-muscle  (jervine).  Chiefly,  if  not  solely, 


CARDIAC    DEPRESSANTS.  369 

through  a  centric  influence,  it  causes  violent  vomiting,  and  in  rare  cases, 
•when  there  is  in  it  an  excess  of  the  veratroidine,  purging.  On  the  motor 
side  of  the  spinal  cord  it  acts  as  a  powerful  depressant,  but  is  without 
influence  upon  the  cerebrum,  the  motor  nerves,  and  the  muscles.  Prob- 
ably, on  account  of  the  vaso-motor  paralysis  "which  it  produces  favoring 
an  increase  of  heat-dissipation,  it  decidedly  lowers  animal  temperature, 
a  fall  of  as  much  as  four  or  even  more  degrees  sometimes  occurring  in 
the  poisoned  lower  animals  before  death. 

THERAPEUTICS. — With  our  present  knowledge  of  the  physiological 
action  of  veratrum  viride,  it  is  evident  that  there  are  only  two  rational 
indications  for  its  use, — namely,  to  reduce  spinal  action  and  to  reduce 
arterial  action.  Owing  to  the  very  great  effect  veratrum  viride  has  upon 
the  circulation,  and  to  the  numerous  drugs  which  are  purer  spinal  depress- 
ants, it  is  rarely  called  on  to  meet  the  first  indication,  and  in  practice 
should  simply  be  used  to  lessen  the  force  of  the  circulation. 

Veratrum  viride  has  been  recommended  in  mania  a  potu  ;  and  in  cases 
of  irritation  of  the  brain  from  drink,  with  strong  bounding  pulse,  it  may 
be  of  great  service  ;  but  in  the  true  delirium  tremens,  with  universal  ady- 
namia, it  is  a  thoroughly  improper  remedy,  capable  of  deepening  the  pros- 
tration into  fatal  exhaustion  ;  indeed,  we  have  known  of  death  occurring 
in  this  disease  from  its  use. 

When  true  sthenic  arterial  excitement  is  to  be  combated  in  any  dis- 
ease, except  it  be  gastritis,  veratrum  viride  may  be  employed  as  a  prompt, 
thoroughly  efficient,  and  at  the  same  time  very  safe  remedy, — very  safe, 
since  it  is  almost  incapable  of  producing  death  in  the  robust  adult,  unless 
used  with  great  recklessness  and  in  repeated  doses.  In  the  early  stages 
of  sthenic  pneumonia  it  offers,  we  believe,  the  best  known  method  of 
reducing  the  pulse-rate  and  the  temperature,  and  of  lessening  the  con- 
gestion.* It  is  hardly  necessary  to  mention  other  individual  diseases  in 
which  veratrum  viride  may  be  employed  to  carry  out  the  present  indica- 
tion. In  peritonitis  its  tendency  to  cause  vomiting  is  very  much  against 
its  use,  and,  unless  this  action  can  be  controlled,  should  interdict  its  em- 
ployment. 

In  chronic  cardiac  diseases  it  may  be  used  in  precisely  those  cases  in 
which  digitalis  is  contra-indicated, — i.e.,  where  there  is  excessive  hyper- 
trophy ;  but,  on  account  of  its  less  persistent  influence  and  greater  ten- 
dency to  disturb  digestion,  it  is  usually  less  advantageous  than  is  aconite. 

The  centra-indications  to  the  use  of  veratrum  viride  are  cardiac  weak- 
ness and  the  existence  of  general  adynamia.  As  an  emetic,  veratrum 
viride  should  never  be  employed. 

TOXICOLOGY. — Although  veratrum  viride  is  a  remedy  of  great  power, 
capable  of  producing  the  most  alarming  symptoms,  yet  it  is  the  safest  of 
the  cardiac  depressants.  Overdoses  of  it  provoke  vomiting  so  soon  and 
so  certainly  that  it  is  somewhat  doubtful  whether  a  robust  adult  could 


*  Compare  Oulmont  {Bulletin  de  Tlierapeutiqite,  Ixxiv.  146)  and  Zuber  and  H.  Hirtz 
(find.,  Ixxvi.  468). 

24 


370  GENERAL  REMEDIES. 

be  killed  by  a  single  dose  of  any  of  its  official  preparations,  especially  if 
prompt  and  judicious  treatment  were  afforded. 

\Ye  have  several  times  known  a  teaspoonful  of  its  fluid  extract  to  be  taken,  and 
Percy  cites  recoveries  after  the  ingestion  of  a  tumblerful  of  the  tincture  ;  after  thirty 
grains  of  the  resinoid  ;  after  two  doses — a  tumblerful  each — of  a  syrup  represent- 
ing a  pound  of  the  root  to  the  pint.  A  feeble  child,  eighteen  months  old,  was 
killed  by  thirty-five  drops  of  the  tincture,2  and  a  doubtful  case  of  fatal  poisoning  in 
the  adult  is  mentioned.3  J.  D.  Blake4  reports  a  death  resulting  from  the  admin- 
istration of  between  three  and  four  drops  of  Norwood's  tincture  every  two  hours 
to  a  babe  eleven  months  old  ;  and  a  man  convalescing  from  typhoid  fever  was 
killed  by  a  drachm  of  the  fluid  extract.5 

In  cases  of  poisoning,  vomiting  should  be  encouraged  by  large 
draughts  of  warm  water  until  the  stomach  is  well  washed  out.  Then 
the  patient  should  be  forced  to  lie  flat  upon  the  back,  with  the  head 
lower  than  the  feet,  and  the  efforts  at  vomiting  should  be  restrained.  If 
they  cannot  be  checked,  and  if  the  prostration  be  severe,  on  no  account 
should  the  patient  be  allowed  to  rise  up,  but  must  be  made  to  vomit  into 
a  towel.  A  full  dose  of  laudanum  should  be  given  by  the  rectum,  and 
brandy  or  whiskey  be  administered  by  the  mouth.  Tincture  of  digitalis 
and  strychnine  should  be  given  hypodermically.  We  have  noticed  that 
spirits  will  sometimes  be  retained  only  when  given  undiluted,  and  in  such 
form  will  quiet  the  stomach  at  once.  If  the  stomach  refuses  alcohol  in 
any  shape,  the  rectum  should  be  made  use  of.  Ammonia  may  be  em- 
ployed as  an  adjuvant  to  alcohol.  External  heat  is  important,  and  mild 
flagellations,  rubbing  with  coarse  towels,  sinapisms,  etc. ,  may  be  used  to 
keep  up  the  external  capillary  circulation. 

ADMINISTRATION. — In  acute  diseases  veratrum  viride  should  always 
be  given  in  increasing  doses  until  its  physiological  action  is  manifested. 

In  almost  all  cases  vomiting  is  to  be  avoided  as  far  as  possible.  To  do  this, 
small  quantities  of  the  drug  may  in  some  cases  be  given  every  hour,  and  corre- 
sponding doses  of  laudanum  (five  to  ten  drops)  should  be  exhibited  fifteen  minutes 
before  each  dose  of  veratrum  viride. 

Dose  of  fluid  extract  (FLUIDEXTRACTUM  VERATRI,  U.  S. ),  one  to 
three  minims  (0.06-0.18  C.c. );  of  tincture  (TINCTURA  VERATRI — ten 
per  cent.,  U.  S. ),  ten  to  thirty  minims  (0.8-2.0  C.c.). 

As  already  stated,  these  new  official  preparations,  are  less  desirable 
than  those  from  veratrum  viride,  Dose  of  fluid  extract  one  to  three  min- 
ims (0.06-0.18  C.c. ),  of  tincture  U.  S.  P.,  1890,  five  to  ten  minims 
(04. -0.8  C.c.). 

VERATRINA.     U.  S. 

This  alkaloid  is  procured  from  the  seeds  of  Asagraea  officinalis 
(Veratrum  Sebadilla*).  As  found  in  commerce,  it  is  almost  always  more 

t  The  action  of  sabadilline,  the  congeneric  alkaloid  of  veratrine,  has  been  partially 
studied  by  I.  Urpav  (Montpellier  Mid.,  1883,  i.  274),  who  finds  it  to  have  only  about  one- 
twelfth  the  toxic  power  of  veratrine. 


CARDIAC   DEPRESSANTS.  371 

or  less  impure,  and  occurs  as  a  grayish-white  powder  of  an  intensely 
acrid  taste,  and  producing,  even  in  the  minutest  quantity,  when  smelled, 
frequently  repeated  sneezing,  which  may  continue  for  hours. 

PHYSIOLOGICAL  ACTION. — Veratrine  is  exceedingly  irritating  to  any 
surface  it  may  come  in  contact  with,  producing  when .  given  hypoder- 
mically  or  endermically  severe  pain,  and  when  rubbed  on  the  skin  a  feel- 
ing of  warmth,  followed  by  prickling,  severe  pain,  numbness,  and,  if  its 
use  be  persisted  in,  a  marked  redness.  On  the  mucous  membranes  its 
action  is  even  more  decided.  In  the  nostrils  the  minutest  portion  of  it 
produces  intense  irritation,  as  shown  by  repeated  sneezing  and  free  dis- 
charge, which  may  be  bloody.  Upon  the  tongue  a  speck  causes  burning, 
with  free  salivation.  When  taken  internally,  in  small  doses,  it  causes 
slowing  and  weakening  of  the  pulse  ;  more  freely  administered,  indica- 
tions of  gastro-intestinal  irritation  ;  and  in  large  doses  it  is  followed  by 
violent  vomiting,  serous  purging,  often  with  intense  burning  in  the  mouth 
and  throat,  and  general  muscular  weakness.  No  fatal  case  of  poisoning 
is  on  record  ;  *  but  in  the  experiments  of  Esche  on  himself  a,  half-grain  of 
the  acetate  produced  collapse,  with  a  pale,  cold,  wet  skin,  pinched  feat- 
ures, a  rapid,  thready,  irregular  pulse,  violent  vomiting,  and  marked 
muscular  tremblings.  Other  observers  have  noted  more  pronounced 
indications  of  convulsions  ;  and,  according  to  Bardsley,  when  absorbed 
through  the  skin,  instead  of  purging  it  produces  in  some  cases  very  free 
diuresis. 

Although  official,  veratrine  is  almost  never  used  in  practical  medicine, 
and  we  therefore  merely  epitomize  our  knowledge  of  its  physiological 
action,  referring  the  reader  to  the  tenth  edition  of  this  treatise  for  its 
more  elaborate  study. 

Veratrine  is  primarily  a  muscle-poison. 

When  a  muscle  during  the  convulsive  stage  of  veratrine-poisoning  is 
momentarily  stimulated,  instead  of  the  usual  momentary  contraction  a 
prolonged  tetanic  spasm  results  and  lasts  some  seconds  :  this  spasm  is 
induced  by  the  slightest  irritation.  When  the  supplying  nerve  is  irritated 
repeatedly  within  a  short  time,  the  muscle  loses  its  power  of  entering  upon 
a  "veratrine  contraction,"  but  if  left  quiet  for  a  time  recovers  itself. 
There  is,  therefore,  in  veratrine-poisoning,  preceding  the  stage  of  muscu- 
lar paralysis,  a  stage  of  muscular  hyperexcitability.  It  can  scarcely  be 
doubted  that  this  is  the  result  of  an  action  not  upon  the  nerve-endings, 
but  upon  the  sarcolemma  of  the  muscle,  f  Finally,  if  the  dose  of  vera- 

*  In  S/.  George's  Hospital  Reports,  1870,  v.,  C.  Paget  Blake  reports  a  case  of  recovery 
after  the  ingestion  of  a  liniment  supposed  to  contain  three  grains  of  veratrine !  Intense 
itching  of  the  skin  was  a  prominent  symptom. 

t  Pick  and  Boehm  believe  that  they  prove  that  the  prolongation  of  the  muscular 
contractions  in  veratrine-poisoning  is  due  to  a  greater  intensity  of  the  chemical  pro- 
cesses of  the  muscles,  and  not  to  a  delay  of  the  process  of  restitution.  A  discussion 
of  this  point  would  involve  that  of  muscular  physiology,  and  cannot  be  entered  into  here. 
The  weak  point  of  the  argument  made  by  Pick  and  Boehm  may,  however,  be  pointed 
out.  Granting  all  their  asserted  facts,  it  is  perfectly  possible  that  greater  intensity  of 
the  chemical  processes  is  an  effect,  not  a  cause,  of  the  prolonged  contractions. 


,372  GENERAL  REMEDIES. 

trine  has  been  large  enough,  the  muscle  becomes  contracted,  stiff,  fails  to 
respond  to  any  irritant  whatever,  and  exhibits  the  acid  reaction  of  post- 
mortem rigidity. 

On  the  cerebrum  veratrine  has  probably  little  action. 

It  is  impossible  at  present  to  reconcile  the  discord  of  investigators  as 
to  the  influence  of  the  drug  upon  the  spinal  cord.  It  is  probable  that  it 
acts  directly  as  a  paralyzant  on  both  motor  and  sensory  nerves.  It  is  a 
powerful  depressant  to  the  respiratory  centre,  killing  chiefly  by  the  pro- 
duction of  asphyxia,  and  acts  upon  the  heart-muscle  and  probably  upon 
the  muscles  in  the  coats  of  the  arteries  as  upon  voluntary  muscles  ;  in  the 
beginning,  by  its  influence  on  the  heart  and  arteries,  it  temporarily  in- 
creases the  blood-pressure,  but  soon  lowers  it,  the  pulse  being  in  the 
early  stages  of  the  poisoning  slowed,  largely  by  the  stimulant  influence 
upon  the  inhibitory  apparatus. 

THERAPEUTIC  ACTION. — Veratrine  was  formerly  recommended  in 
acute  rheumatism  and  in  dropsy,  but  with  the  growth  of  the  modern 
materia  medica  this  employment  of  it  is  unjustifiable.  It  is  sometimes 
used  as  an  irritant  applied  to  the  spine  and  to  the  skin  of  the  affected 
muscle  in  certain  palsies,  and  the  U.  S.  Pharmacopoeia  recognizes  an 
ointment  (i  to  25)  for  this  purpose  and  for  use  in  neuralgia.  One-six- 
teenth of  a  grain  of  veratrine  has  produced  most  alarming  symptoms. 
It  is  absorbed  readily  through  the  skin,  and,  even  if  used  externally,  is  a 
more  dangerous  than  useful  remedy. 

ARNICA.* 

Formerly  the  U.  S.  Pharmacopoeia  recognized  both  the  rhizome  and 
flowers  of  the  Arnica  montana,  a  perennial  composite,  native  of  Northern 
Europe  and  Asia,  and  said  also  to  be  found  in  the  Northwestern  United 
States,  but  at  present  only  the  flowers  are  official  under  the  name  of 
Arnica.  The  yellow  flowers  have  about  fourteen  striated  ligulate  triden- 
tate  florets  in  the  ray,  twice  as  long  as  the  disk,  which  consists  of  numerous 
tubular  florets.  Of  its  two  alkaloids,  arnicinc  and  cytisinc,^  the  latter  is 
said  to  be  identical  with  the  active  principle  of  the  laburnum  {Cytisus 
laburnum). 

PHYSIOLOGICAL  ACTION. — Locally,  arnica  is  stimulating,  and,  if  in 
sufficient  strength,  decidedly  irritating.  Upon  some  skins  the  tincture 
acts  even  violently,  rapidly  developing  an  acute  eczematous  inflamma- 
tion of  the  upper  dermal  layers,  as  manifested  by  hypersemia,  papules, 
vesicles,  excoriations,  crusts,  and  scales  in  regular  sequence.1 

Neither  the  symptoms  of  poisoning  by  arnica  nor  its  physiological 
action  are  well  made  out. 


*  This  drug  probably  does  not  belong  in  the  present  class. 

t  J.  L.  Prevost  and  Paul  Binet  find  that  cylisine  is  a  powerful  centric  emetic,  which 
in  large  doses  paralyzes  the  motor  nerves.  Its  direct  action  upon  the  circulation  is  very 
slight ;  toxic  doses  cause  a  gradual  lowering  of  arterial  pressure  and  death  by  respiratory 
paralysis  (Revue  Med.  de  la  Suisse  Rom.,  vii.  and  viii.,  1887 ;  see  also  R.  Radziwillowicz, 
Thesis,  Dorpat,  1887). 


CARDIAC    DEPRESSANTS.  373 

According  to  H.  A.  Hare,2  the  fluid  extract  in  doses  of  five  to  ten  drops  pro- 
duces in  the  dog  a  slowing  of  the  cardiac  beats,  with  increase  of  the  fulness  of  the 
pulse-wave  and  a  very  slight  increase  of  the  arterial  pressure,  the  slowing  of  the 
pulse  being  the  result  of  a  stimulation  of  the  pneumogastric  nerves,  and  the  slight 
increase  of  the  arterial  pressure  probably  caused  by  increased  heart-work.  After 
large  doses  the  pulse  becomes  very  rapid,  from  pneumogastric  paralysis,  the  arterial 
pressure  remaining  near  the  normal.  Viborg  (quoted  by  Still£)  affirms  that  in  horses 
and  cows  it  causes  increased  action  of  the  heart,  flow  of  urine,  and  warmth  of  skin, 
followed  by  very  decided  general  depression. 

According  to  Still6,  the  effects  of  moderate  doses  on  man  are  similar 
to  those  noted  as  occurring  in  the  lower  animals, — namely,  increase  of 
the  cardiac  action,  of  the  respiration,  of  the  temperature  of  the  skin, 
and  of  the  perspiration  and  urine,  along  with  very  decided  symptoms  of 
gastric  irritation.  On  the  other  hand,  it  is  asserted  that  ten  drops  of 
the  tincture  every  three  or  four  hours  act  as  a  decided  arterial  depressant 
(C.  C.  Balding3).  The  symptoms  of  poisoning  seem  strangely  to  vary 
between  those  of  a  violent  gastro- intestinal  irritant  and  those  of  a  nar- 
cotic poison. 

Thus,  in  a  woman,  two  cups  of  a  strong  infusion  produced  violent  gastro- 
intestinal irritation,  as  shown  by  vomiting  and  choleraic  diarrhoea,  reduction  of  the 
pulse  to  60,  and  finally  collapse.4  In  Barbier's  case  (quoted  by  Stille"),  an  infusion 
of  eighty  grains  of  the  flowers  caused  giddiness  and  intense  muscular  weakness, 
with  spasmodic  movements  of  the  limbs.  In  another,5  not  fatal,  case,  according  to  the 
statement  of  the  patient,  an  ounce  of  the  tincture  did  not  produce  any  symptoms  for 
eight  hours,  when  approaching  collapse,  dilated,  immovable  pupils,  with  a  cold,  dry 
skin  and  a  feeble  fluttering  pulse,  rapidly  supervened  upon  an  intense  epigastric 
pain,  which  was  increased  by  pressure.  In  a  not  fatal  case  reported  by  W.  A. 
Thorn,6  four  hours  after  ingestion  of  a  fluidounce  of  a  tincture  by  a  young  man,  the 
pulse  was  100,  full  and  strong,  the  temperature  normal,  insensibility  complete,  con- 
junctiva anaesthetic,  respirations  18  per  minute,  no  vomiting  or  purging.  Twelve 
hours  later  the  patient  became  wildly  delirious ;  the  next  day  he  suffered  from 
burning  pain  in  the  abdomen,  diarrhoea,  and  free  diuresis. 

THERAPEUTICS. — In  the  present  state  of  our  knowledge,  the  internal 
use  of  arnica  is  experimental.  Externally  it  is  employed  as  a  stimulant 
application  in  bruises  and  sprains,  generally  in  the  form  of  tincture 
(TiNCTURA  ARNICA — twenty  per  cent.,  U.  S.),  which  may  be  applied 
pure.  Sometimes  fomentations  of  the  flowers  are  employed.  Its  prop- 
erty of  occasionally  producing  intense  dermal  irritation  should  be  borne  in 
mind. 

ACONITUM— ACONITE.     U.  S. 

The  Aconitum  Napellus,*  or  monkshood,  is  a  tall  perennial,  indige- 
nous in  Europe,  and  cultivated  in  this  country  for  the  sake  of  its  spike 


*  All  the  species  of  the  genus  Aconitum  are  more  or  less  poisonous,  although  A. 
Napellus  is  the  only  one  official.  For  a  study  of  the  comparative  strength  of  the  various 
aconites,  see  Schroff  (Journal  fur  Pharmacodynamik,  1857,  335).  He  arranges  them  as 
follows,  commencing  with  the  most  virulent :  A.ferox,  A.  Napellus,  with  its  varieties, 
neomontanum,  tauricum,  and  variabile,  A.  Cammarum,  A.  paniculalum,  A.  Anthora. 


374  GENERAL  REMEDIES. 

of  blue  flowers.  The  leaves  are  three  or  four  inches  in  diameter,  and 
cut  almost  to  the  base  into  from  three  to  seven  three-lobed,  wedge-shaped 
divisions. 

The  root,  which  is  the  only  official  portion,  is  from  three  to  four 
inches  long,  very  tapering,  about  three-quarters  of  an  inch  in  diameter 
at  the  base.  Its  taste  is  bitterish,  acrid,  and  after  a  little  while  benumb- 
ing, giving  origin  to  intense  tingling  of  the  lips  and  mouth.  It  is  to 
be  distinguished  from  horseradish  root,  with  which  it  has  been  some- 
times fatally  confounded,  by  its  external  brown  color  and  its  lack  of 
odor  when  scraped.  The  whole  plant  is  active  and  tastes  like  the  root. 
The  U.  S.  Pharmacopoeia  requires  that  the  root  shall  contain  not  less  than 
o.  5  per  cent,  of  aconitine. 

In  1833  Geiger  and  Hesse  discovered  in  aconite  the  alkaloid  aconitine. 
According  to  the  most  recent  researches,  there  are  in  the  rhizome,  how- 
ever, besides  aconitine,  two  alkaloids,  benzaconine  and  aconine,  which 
may  also  be  made  by  the  hydrolysis  of  aconitine,  benzaconine  being  the 
isaconitine,  and  the  principal  constituents  of  the  napelline  and  the  picraco- 
nitine  of  older  writers  (Cash  and  Dunstan1). 

Aconitine,  U.  S. ,  occurs  in  colorless  or  whitish,  odorless,  rhombic 
tables  or  prisms.  In  extremely  dilute  solution  it  is  capable  of  producing 
a  characteristic  tingling  of  the  tongue  or  lips,  but  is  so  poisonous  that  it 
should  never  be  tasted  unless  in  solution  of  no  greater  strength  than  one 
part  in  five  thousand,  and  even  then  with  great  caution.  Amorphous 
aconitine  of  commerce  is  a  more  or  less  impure  mixture,  containing  de- 
composition products. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Aconite  and  aconitine  are 
locally  irritant,  but  this  irritant  influence  is  soon  overwhelmed  by  the 
effect  of  the  drug  upon  the  peripheral  ends  of  the  sensory  nerves,  so  that 
numbness  and  tingling  are  produced  at  the  point  of  application.  More- 
over, the  general  influence  of  the  drug  is  so  overwhelming  that  the  local 
effect  counts  for  very  little  in  practical  medicine. 

Absorption  and  Elimination. — Aconite  yields  its  alkaloids  with  great 
rapidity  to  absorption,  and  aconitine  is  capable  of  passing  through  the 
mucous  membranes  and  even  the  skin,  making  it  in  pure  form  a  danger- 
ous external  remedy.  Concerning  its  elimination  we  have  no  knowledge. 

General  Action. — The  symptoms  which  are  induced  by  small  thera- 
peutic doses  of  aconite  in  man  are  reduction  of  the  force  and  frequency 


The  toxic  properties  of  A.  Anthora  are  very  weak.  Lycoctonine  is  the  alkaloid  of  A. 
lycoctonum.  For  a  physiological  study  of  it  by  Ott,  see  Phila.  Med.  Times,  vi.  25. 

Pseudaconiline,  the  alkaloid  of  Aconitum  ferox,  has  been  physiologically  studied 
by  Boehm  and  Ewens  (A.  E.  P.  P.,  1873,  i.)  and  by  Cash  and  Dunstan  (P.  Tr.  R.  S.  L., 
Series  B.,  1902),  who  are  in  accord  in  finding  that  its  physiological  action  is  that  of  aco- 
nitine save  only  in  regard  to  strength :  0.4  grain  of  it  is  said  to  be  equivalent  in  toxic 
power  to  0.45  of  true  aconitine.  Japaconitine,  the  alkaloid  of  Japanese  aconite,  Ktiza- 
uzu,  A.japonicum,  and  A.  fischeri,  according  to  Cash  and  Dunstan,  acts  physiologically 
as  true  aconitine,  except  that  0.85  grain  is  equivalent  to  0.9  in  toxicity. 

For  local  application  these  three  alkaloids  may  be  substituted  for  aconitine. 


CARDIAC   DEPRESSANTS.  375 

of  the  circulation,  a  sense  of  muscular  inertia  and  weakness,  and  a  slight 
tingling  in  the  extremities  or  in  the  lips.  If  the  dose  administered  is  large, 
all  these  symptoms  are  intensified  ;  the  muscular  weakness  is  extreme  ;  the 
tingling  is  felt  all  over  the  body  ;  the  pulse  is  feeble,  and  reduced  to  30  or 
40  per  minute  ;  the  respirations  are  diminished  ;  giddiness  and  disordered 
vision  may  be  manifested,  especially  when  the  erect  posture  is  assumed. 
After  three  or  four  hours  these  symptoms  gradually  subside. 

When  a  poisonous  dose  has  been  ingested,  the  first  thing  noticed  in 
most  cases  is  a  burning  or  tingling  in  the  throat  or  in  the  extremities, 
soon  spreading  over  the  whole  body.  The  pulse  rapidly  falls  in  fre- 
quency, and  in  a  very  little  time  becomes  exceedingly  weak,  intermit- 
tent, irregular,  and  finally  imperceptible  ;  the  muscular  strength  is 
greatly  reduced  and  sometimes  almost  entirely  gone  ;  the  respirations 
are  shallow,  feeble,  irregular,  and  infrequent ;  the  general  sensibility  is 
very  much  benumbed,  so  that  marked  anaesthesia  of  the  surface  is  pres- 
ent ;  the  skin  is  bedewed  with  a  cold  sweat ;  the  countenance  is  anxious, 
sunken,  livid,  and  the  eyes  are  often  protruded,  or  are  even  spoken  of 
as  glaring  ;  the  pupil  is  generally  dilated,  but  when  there  are  no  convul- 
sions may  be  contracted  ;  gastric  burning  is  sometimes  complained  of, 
and  severe  vomiting  may  be  present,  but  the  stomach  is  not  rarely  reten- 
tive. The  intellect  generally  remains  unaffected  until  very  near  the  close, 
sometimes  to  the  very  moment  of  death.*  In  the  collapse  of  the  latter 
stages  of  aconite-poisoning  the  special  senses  may  be  lost,  especially  the 
sight.  The  voice  is  very  generally  extinguished.  Convulsions  occur  in 
some  cases,  not  in  others  ;  and  certainly  in  some  instances,  if  not  always, 
the  patient  is  unconscious  during  their  continuance.  Diplopia,  or  other 
disorder  of  vision,  has  been  noted  in  some  cases.  Death  may  occur  sud- 
denly, especially  directly  after  some  exertion  on  the  part  of  the  patient, 
from  syncope. 

The  symptoms  produced  by  aconite  in  the  lower  animals  are  similar  to  those 
caused  by  it  in  man,  the  prominent  manifestations  being  great  disturbance  of  the 
respiration,  muscular  weakness,  vascular  depression,  and  finally  death,  with  or  with- 
out convulsions.  As  we  have  seen  the  rabbit  after  the  injection  of  one-sixth  or  one- 
quarter  grain  of  Morson's  pure  aconitine,  the  animal  commences  to  jump  vertically 
in  a  very  peculiar  manner,  and  often  to  squeal  piteously.  The  jumping  soon  grows 
less  and  less  powerful,  and  finally  is  replaced  by  severe  convulsions,  during  which 
the  animal  often  lies  prostrate  on  its  side.  In  the  dog,  however,  the  muscles  have 
remained  without  a  quiver  during  all  stages  of  the  poisoning  ;  in  the  horse  Harley  * 
has  noticed  convulsions.  The  convulsions  are  an  inconstant  symptom,  dependent 
upon  peculiarities  of  the  individual  or  species,  as  well  as  upon  the  amount  injected. 
Dilatation  of  the  pupil  frequently  occurs,  if  it  be  not,  indeed,  a  constant  phenomenon. 
There  is  often  severe  vomiting.  Death  usually  results  from  asphyxia,  but  if  a  large 
dose  be  given  hypodermically,  may  occur  in  less  than  a  minute,  probably  from 
sudden  paralysis  of  the  heart-muscle. 

*  Laborde  and  Duquesnel  affirm  that  after  very  large  dose  of  aconitine  the  animal 
dies  of  spasm  of  the  glottis  and  diaphragm,  because  they  have  noticed,  especially  in  the 
young  animal,  drawing  in  or  constriction  of  the  lower  chest  during  life,  and  sub-pleural 
ecchymoses  after  death.  These  are,  however,  the  marks  of  paralysis  of  the  glottis  from 
palsy  of  the  recurrent  laryngeal  nerve. 


376  GENERAL  REMEDIES. 

Nervous  System. — The  mental  condition  in  aconite-poisoning  shows 
that  the  drug  has  no  influence  upon  those  portions  of  the  cerebrum 
which  are  connected  with  consciousness  and  intellectuality. 

Owing  to  the  apparent  contradictory  character  of  the  evidence  it  is 
difficult  thoroughly  to  elucidate  the  action  of  aconite  upon  the  lower  por- 
tions of  the  nervous  system  ;  the  phenomena  to  be  accounted  for  are 
sensory  paralysis,  loss  of  reflex  activity,  and,  later  in  the  poisoning,  motor 
palsy. 

Nerves. — The  local  anaesthesia  which  is  produced  by  the  application 
of  aconite  demonstrates  that  the  drug  has,  when  in  sufficient  concentra- 
tion, a  paralyzing  influence  upon  the  sensory  nerves. 

The  persistence  of  voluntary  movement  after  abolition  of  reflex  actions, 
which  was  first  noted  by  Boehm  and  Wartmann,3  and  afterwards  by  Lie"- 
geois  and  Hottot,4  as  well  as  by  Mackenzie,  proves  that  at  a  certain  stage 
of  the  poisoning,  while  the  motor  pathway  from  the  brain  along  the  ante- 
rior columns  and  the  efferent  nerves  is  open,  either  the  sensory  nerves  or 
the  receptive  centres  of  the  cord  are  paralyzed. 

The  discovery  of  Liegeois  and  Hottot — namely,  that  in  the  frog 
poisoned  simultaneously  with  aconite  and  strychnine  there  is  a  certain 
stage  when  no  amount  of  irritation  of  the  nerve  will  induce  convulsion, 
whilst  a  slight  direct  irritation  of  the  cord  will  cause  violent  strychnic 
spasms — would  seem  to  prove  that  at  least  the  earliest  abolition  of  the 
reflex  activity  is  due  to  paralysis  of  the  afferent  nerve-fibres.  In  accord 
with  this,  Mackenzie  found  that  when  a  nerve  is  protected  from  the 
poison  by  tying  its  supplying  artery,  irritation  of  it  causes  reflex  actions 
when  the  remainder  of  the  frog's  periphery  is  insensible  ;  that  there  is 
a  stage  of  poisoning  in  which  irritation  of  the  extreme  peripheral  nerves 
fails  to  induce  reflex  movements,  although  such  movements  are  called  out 
by  irritation  of  the  sensory  nerve-trunk  ;  and  that  in  the  last  stages  of 
the  poisoning  irritation  of  the  trunk  is  powerless,  while  irritation  of  the 
posterior  columns  of  the  cord  still  produces  wide-spread  movements. 
This  evidence  in  its  totality  appears  to  us  to  prove  that  aconite  paralyzes 
the  sensory  nerves,  commencing  at  their  peripheral  endings,  and  that  the 
loss  of  reflex  activity  is  due,  at  least  in  great  part,  to  this  peripheral 
paralysis.  * 

Liegeois  and  Hottot  affirm,  however,  that  in  the  aconitized  frog  loss  of 
sensibility  occurs  at  a  time  when  the  reflex  activity  is  intact.  If  this  ex- 
perimental fact  be  correct,  it  would  seem  to  be  an  inevitable  conclusion 
that  the  primary  anaesthesia  has  its  seat  above  the  mechanism  involved  in 

*  Laborde  and  Duquesnel  (Des  Aconits,  Paris,  1883,  103)  believe  that  they  have  de- 
monstrated that  aconitine  does  not  act  upon  the  sensory  nerves.  Their  chief  experiments 
consisted  in  tying  the  vessels  of  a  dog's  leg  in  such  a  way  that  no  blood  could  return  to 
the  body,  and  injecting  the  alkaloid  into  the  limb,  after  cutting  the  nerve.  Under  these 
circumstances  they  found  that  galvanization  of  the  centric  end  of  the  nerve  continued  to 
elicit  response.  At  most  such  experiments  prove  nothing  as  to  the  action  of  the  poison 
upon  the  peripheral  nerve-endings.  Moreover,  it  remains  uncertain  whether  the  aco- 
nitine really  came  in  contact  with  the  divided  nerve,  as  all  circulation  in  the  limb  must 
have  been  arrested. 


CARDIAC   DEPRESSANTS.  377 

reflex  acts,  or,  in  other  words,  in  the  perceptive  centres  of  the  brain, 
This  theory  is  strongly  urged  by  the  French  investigators  mentioned, 
who  further  affirm  that  tying  the  aorta  close  to  its  abdominal  bifurcation, 
so  as  to  prevent  access  of  the  blood — i.e.,  of  the  poison — to  the  posterior 
nerves,  does  not  affect  the  development  of  the  anaesthesia  ;  also,  that 
closing  the  artery  nearer  its  origin  in  such  a  way  as  to  shut  off  the  circu- 
lation to  the  cord  and  spinal  nerves,  but  to  allow  the  passage  of  the  blood 
to  the  cerebrum,  does  not  cause  sensory  paralysis  to  come  on  more  slowly 
than  is  normal  in  poisoning  by  aconite.  Further,  according  to  Li£geois 
and  Hottot,  in  the  frog  doubly  poisoned  by  aconite  and  strychnine  there 
is  a  period  in  which  reflex  tetanic  convulsions  occur,  although  there  is 
marked  aconitic  anesthesia.* 

If  the  facts  just  enumerated  be,  as  affirmed,  correct,  the  conclusion 
seems  to  be  almost  inevitable  that  aconite  influences  the  higher  perceptive 
centres  or  general  sensibility  before  it  affects  the  peripheral  sensory  nerves. 
S.  Ringer  and  H.  Murrell 5  deny,  however,  the  accuracy  of  the  delicate 
experiments  of  Liegeois  and  Hottot,  so  that  at  present  writing  the  matter 
remains  in  doubt.f 

In  regard  to  the  action  of  the  drug  upon  the  motor  nerves  the  evi- 
dence is  somewhat  contradictory.  According  to  Achscharumow,  when 
a  frog  is  poisoned  after  the  abdominal  aorta  has  been  tied,  reflex  and  vol- 
untary activity  is  preserved  in  the  hind  legs  long  after  it  has  been  lost  in 
the  anterior  portion  of  the  body  ;  and,  at  the  same  time,  while  the  brachial 
nerves,  as  tested  by  galvanic  stimulation,  have  lost  their  power  of  trans- 
mitting impulses,  the  protected  ischiatic  nerves  have  preserved  their  func- 
tional ability.  P.  C.  Plugge6  confirms  these  statements,  and  also  affirms 
that  it  is  especially  the  peripheral  ends  of  the  motor  nerves  which  are 
affected,  since  when  in  the  frog's  leg  the  lower  portion  had  been  protected 
from  the  poison,  galvanization  of  the  nerve-trunk  a  considerable  distance 
above  the  point  of  protection  caused  response  in  the  tributary  muscles. 

These  allegations  would  seem  to  prove  that  aconitine  paralyzes  the 
peripheral  motor  nerves,  but  are  directly  contradicted  by  Boehm  and  Wart- 
mann,  by  Li6geois  and  Hottot,  by  Mackenzie7  and  by  A.  Guillaud,8  who 
affirm  that  the  nerves  and  muscles  in  poisoned  animals  preserve  almost 
entirely  their  normal  excitability  until  death,  and  that  shutting  off  access 
of  the  poison  to  the  limb  by  tying  does  not  affect  the  development  of 
motor  paralysis  under  the  action  of  aconite. 

*  Later  in  the  poisoning  the  extreme  peripheral  nerves  become  affected,  so  that  irri- 
tation of  the  skin  in  the  doubly  poisoned  frog  will  not  provoke  convulsions,  even  at  a 
time  when  irritation  of  the  trunk  of  a  nerve  produces  general  reflex  motor  disturbance. 
At  last  galvanization  of  the  nerve-trunk  itself  fails  to  induce  response. 

t  Curiously  enough,  Ringer  and  Murrell,  while  doubting  the  experiments  of  Liegeois 
and  Hottot,  accept  the  conclusion  founded  upon  these  asserted  erroneous  experiments, 
seemingly  because  they  themselves  have  found  that  aconitine  causes  abolition  of  reflex 
action  more  rapidly  in  brainless  than  in  normal  frogs.  It  is  evident  that  even  if  this  were 
invariably  the  case  it  would  in  no  way  prove  the  conclusions  of  Liegeois  and  Hottot. 
Further,  the  experiments  on  brainless  frogs  were  only  three  in  number,  and  it  is  probable 
that  the  rapid  reflex  palsy  was  simply  the  result  of  batrachian  idiosyncrasies. 


378  GENERAL  REMEDIES. 

The  explanation  of  this  conflict  of  testimony  is  not  to  be  found,  as 
has  been  suggested  by  C.  Ewers,'  in  the  use  of  different  species  of  frogs, 
because  Plugge  employed  various  species  ;  nor  is  it  in  the  employment  of 
different  commercial  aconitines,  because  Plugge  experimented  with  all  the 
varieties,  and  found  them  to  vary  in  power,  but  not  in  quality  of  action. 
Those  observers  who  have  found  least  influence  upon  the  motor  nerves 
acknowledge  some  slight  effect,  and  that  when  aconitine  is  brought  in 
contact  with  an  exposed  nerve  it  rapidly  destroys  its  functional  activity  ; 
also  that  after  death  in  the  aconitized  frog  the  motor  nerves  lose  their 
irritability  more  rapidly  than  normal  (Li6geois  and  Hottot,  Guillaud,  S. 
Ringer  and  H.  Murrell,  Laborde  and  Duquesnel10). 

From  the  evidence  which  has  been  thus  epitomized  it  seems  to  us  that 
the  most  probable  conclusion  is  that  aconite  exerts  a  feeble  depressing 
influence  upon  the  motor  nerves. 

Spinal  Cord. — Our  knowledge  of  the  action  of  aconite  and  its  alka- 
loids upon  the  spinal  cord  is  not  complete  ;  Boehm  and  Wartmann,  Guil- 
laud, Mackenzie,  and  Cash  and  Dunstan  believe  that  after  minute  doses  of 
aconitine  there  is  primarily  excitement  or  stimulation  of  the  motor  cen- 
tres of  the  cord  ;  Mackenzie  affirms  that  the  convulsions  which  are  so 
severe  in  the  frog  after  small  quantities  of  aconite  are  chiefly  of  spinal 
origin,  though  he  believes  that  the  peripheral  motor  apparatus  shares  the 
motor  stimulation.  If  the  primary  stimulation  of  the  cord  really  occurs 
in  mammals,  it  must  be  completely  masked  ;  at  least  we  found  in  a  series 
of  experiments  that  when  the  spinal  cord  was  cut  in  the  mammal  it  was 
not  possible  to  produce  aconitic  convulsions  in  those  portions  of  the  body 
separated  from  cerebral  influence,  and  no  evidences  of  spinal  excitement 
are  ever  seen  in  human  poisoning.  The  conclusion  of  Boehm  and  Wart- 
mann, that  in  the  later  stages  of  the  poisoning  there  is  depression  of  the 
motor  side  of  the  spinal  cord,  is  probably  correct,  but  so  far  as  we  know  has 
never  been  actually  proved.  The  preservation  of  voluntary  movements 
in  the  poisoned  frog  after  the  abolition  of  sensation  and  of  the  reflexes 
shows  that  the  motor  paths  from  the  brain  to  the  cord  through  the  mus- 
cle are  preserved  at  the  time  when  the  afferent  apparatus  is  completely 
paralyzed,  and  that  the  action  of  aconite  on  the  motor  spinal  cord  is 
entirely  subservient  to  its  influence  on  the  peripheral  nerves. 

Muscles. — The  early  evidence  in  regard  to  the  action  of  aconite  upon 
the  muscles  was  entirely  contradictory,  Wieland,  Bucheim,  and  Eisen- 
menger  affirming  that  the  muscle-curve  is  much  affected  by  the  drug, 
Murray  and  Boehm  and  Wartmann  that  it  remains  unaffected.  The  re- 
searches of  Cash  and  Dunstan  seem,  however,  to  prove  that  aconitine 
does  not  increase  the  irritability  of  the  muscle-fibre,  nor  when  given  in 
moderate  doses  affect  its  capacity  for  work,  though. in  some  way  it  pre- 
disposes the  muscle  to  asynchronism  in  the  contraction  of  its  bundles  of 
fibres. 

Respiration. — Cash  and  Dunstan  having  noticed  primary  increase  of 
the  rate  of  the  respiration  by  aconitine,  believe  that  the  alkaloid  acts  pri- 


CARDIAC   DEPRESSANTS.  379 

marily  as  a  centric  respiratory  stimulant ;  but  until  it  has  been  definitely 
proved  that  the  amount  of  air  forced  in  and  out  of  the  lungs  is  increased 
by  aconitine,  it  must  remain  doubtful  whether  it  ever  has  any  true  stimulant 
effect.  When  the  poisoning  is  advanced  the  respirations  in  the  mammal 
are  slow,  with  a  prolonged  expiration  following  immediately  upon  the  inspi- 
ration. After  the  expiration  there  is  a  long  pause,  so  that  the  whole  breath- 
ing-cycle resembles  very  much  that  occurring  after  section  of  the  vagi.  The 
known  influence  of  aconite  upon  the  peripheral  afferent  nerves  in  general 
suggests  that  the  poison  disturbs  respiration  by  paralyzing  the  peripheral 
afferent  fibres  of  the  vagi,  but  Mackenzie  states  that  in  the  aconitized  animal 
section  of  the  vagi  produces  no  effect  on  the  respiration  ;  and  Boehm  and 
Wartmann  affirm  that  aconite  produces  its  usual  effect  after  division  of 
the  vagi.  It  is  plain  that  even  if  the  aconite  does  paralyze  the  peripheral 
afferent  vagi  it  must  also  act  upon  the  respiratory  centres,  since  arrest  of 
respiration  could  not  be  caused  by  afferent  palsy.  As  the  arrest  occurs 
in  the  frog  before  the  motor  nerves  are  affected  by  the  poison,  Liggeois 
and  Hottot  believe  that  the  disturbance  is  centric  ;  and  we  think  there 
can  be  no  doubt  that  aconite  is  a  direct  depressant  and  paralyzant  of  the 
respiratory  centres. 

Circulation. — The  action  of  aconite  upon  the  circulation  is  very  de- 
cided. In  man  it  causes  first  slowing  and  later  rapidity  with  irregularity 
of  the  pulse,  accompanied  by  a  fall  of  the  arterial  pressure,  which  pro- 
gressively increases  to  the  end.  In  frogs  the  phenomena  caused  by  aco- 
nitine are  similar  to  those  seen  in  man,  and  consist  of  at  first  a  reduc- 
tion and  afterwards  an  increase  in  the  rate  of  the  heart's  beat,  with  a 
loss  of  power  in  the  circulation,  and  finally  irregular  systolic  movements, 
with  marked  prolonged  diastolic  pauses  ending  in  diastolic  arrest  (Ach- 
scharumow,11  Boehm  and  Wartmann). 

In  the  mammal  the  general  influence  of  aconite  upon  the  circulation 
seems  the  same  as  in  man,  except  that  both  in  rabbits  and  in  dogs  a  brief 
rise  of  pressure  is  affirmed  to  precede  the  fall  (Boehm  and  Wartmann, 
Laborde,  Duquesnel).  It  is  probable,  however,  that  this  rise  of  press- 
ure is  secondary,  and  not  directly  caused  by  the  poison.  Very  early  the 
blood-pressure  begins  to  fall  ;  after  a  time  the  fall  becomes  pronounced, 
and  the  pulse,  which  has  been  at  first  slowed,  grows  rapid.  Then  what 
is  known  by  some  observers  as  the  characteristic  condition  develops, 
consisting  especially  of  great  and  rapid  fluctuations  of  pressure,  which 
may  in  the  dog  amount  to  fifty  millimetres  of  mercury,  and  may  for  the 
moment  even  carry  the  pressure  to  a  higher  than  the  normal  point.  The 
pulse  finally  becomes  extremely  rapid  and  irregular  ;  the  heart  is  in  a  con- 
dition of  delirium,  and  soon  stops  in  diastole. 

During  the  advanced  stages  of  the  poisoning  the  rhythm  of  the  mam- 
malian heart  is  seriously  affected,  the  contractions  of  both  auricle  and 
ventricle  being  very  unequal,  and  the  normal  auricular  and  ventricular 
rhythm  seriously  impaired  (see  S.  A.  Matthews,12  also  J.  T.  Cash  and 
W.  R.  Dunstan).  The  intra-ventricular  pressure  also  varies  greatly,  and 


380  GENERAL    REMEDIES. 

the  whole  action  of  the  heart  is  in  such  a  state  of  confusion  as  most 
seriously  to  interfere  with  the  coronary  supply  and  the  general  mechanism 
of  the  circulation.  After  death  the  cardiac  muscle  fails  to  respond  to 
galvanic  irritation.  * 

The  cardiac  phenomena  which  have  just  been  noted  are  most  clearly 
seen  after  the  use  of  pure  aconitine  (Cash  and  Dunstan),  and  under  these 
circumstances  it  is  affirmed  that  until  the  later  stages  of  the  poisoning 
are  reached  there  is  no  distinct  loss  of  force  in  the  individual  systole,  the 
muscle  itself  not  being  affected. 

In  endeavoring  to  elucidate  the  cause  of  the  cardiac  phenomena  of 
aconite-poisoning  it  is  evident  in  the  first  place  that  aconite  affects  the 
heart  directly.  Achscharumow  affirms  that  aconitine  acts  upon  the  frog's 
heart  removed  from  the  body  as  it  does  upon  the  heart  of  the  normal 
batrachian.  Liegeois  and  Hottot  have  produced  the  ordinary  cardiac 
phenomena  of  aconite -poisoning  by  placing  the  alkaloid  upon  the  heart. 

The  first  question  that  offers  itself  is  as  to  the  cause  of  the  primary 
slow  pulse. 

The  concordance  of  recent  investigators  warrants  the  conclusion  that 
aconite  primarily'  slows  the  heart  by  stimulating  inhibition  ;  the  stimula- 
tion being  chiefly  centric,  but,  if  the  experiments  of  Matthews  be  correct, 
also  in  a  measure  peripheral,  f 

Boehm  and  Wartmann  affirm  that  the  development  of  the  slow  pulse  is  not  pre- 
vented by  the  previous  section  of  the  vagi  or  by  atropinization.  Achscharumow, 
however,  states  that  section  of  the  vagi  performed  during  the  early  stage  of  aconite- 
poisoning  is  followed  by  a  pronounced  immediate  rise  both  in  the  number  of  the  car- 
diac pulsations  and  in  the  arterial-pressure.  Lewin 13  affirms  the  correctness  of  this, 
but  states  that  the  rise  is  of  very  brief  duration,  and  is  soon  followed  by  the  usual 
reduction.  S.  A.  Matthews  states,  however,  that  after  section  of  the  vagi  aconite 
reduces  the  heart's  rate  to  a  slight  extent  only,  and  that  even  this  reduction  is  en- 
tirely prevented  by  the  administration  of  atropine.  Cash  and  Dunstan  affirm  that 
section  of  the  vagi  in  the  period  of  slow  pulse  from  aconite  is  followed  by  an 
immediate  increase  of  the  rapidity  of  the  beat. 

The  rapid  pulse  of  the  advanced  stages  of  aconite-poisoning  is  at- 
tributed by  S.  A.  Matthews  chiefly  to  the  ever-increasing  irritability  of 
the  cardiac  muscle  under  the  action  of  aconitine,  and  to  us  seems  to  be  in 
part  due  to  the  action  of  the- alkaloids  upon  the  heart-muscle,  and  to  be 
also  in  part  the  outcome  of  depression  of  the  peripheral  vagi. 

*  According  to  S.  A.  Matthews,  during  the  period  of  delirium  of  the  ventricle  the 
auricle  can  generally  be  restored  to  regular  contraction  by  cutting  one  of  the  big  veins 
and  allowing  it  to  free  itself  of  the  contents. 

t  The  activity  of  aconite  depends  chiefly  upon  the  aconitine.  According  to  Cash  and 
Dunstan,  benzaconine  chiefly  depresses  the  motor  mechanism  within  the  heart,  also  de- 
presses the  vaso-motor  centre,  causes  slow  pulse  by  vagal  stimulation,  and  is  the  antago- 
nist of  digitalin.  Aconine  is  so  feeble  as  to  be  disregarded  in  considering  the  effect  of 
aconite.  According  to  Cash  and  Dunstan,  it  has  a  curare-like  action  on  the  motor  nerves, 
stimulates  the  roots  of  the  vagi,  strengthens  the  ventricular  systole,  and  does  not  affect 
the  vaso-motor  centres. 


CARDIAC   DEPRESSANTS.  381 

The  evidence  given  by  different  experimenters  in  regard  to  the  condition  of  the 
peripheral  vagi  in  aconite-poisoning  is  somewhat  contradictory.  Boehm  and  Wart- 
mann,  and  Plugge,  affirm  the  existence  of  vagal  paralysis.  S.  A.  Matthews  says 
that  ' '  the  peripheral  inhibitory  mechanism  is  not  paralyzed  by  the  aconitine  during 
the  irregular  stage,  as  is  generally  stated  ;"  but  we  have  no  doubt  as  to  the  accuracy 
of  the  assertion  of  Cash  and  Dunstan,  that,  although  when  the  dose  of  aconitine  has 
been  so  large  as  to  be  rapidly  lethal  the  vagal  terminations  may  not  be  completely 
paralyzed  up  to  death,  when  small  lethal  doses  have  been  used,  complete  peripheral 
vagal  paralysis  may  develop,  or  a  condition  appear,  also  noted  by  Boehm,  in  which 
the  vagi  may  respond  one  minute  to  stimulation  and  refuse  to  respond  the  next. 

Our  knowledge  of  the  action  of  aconitine  upon  the  vaso-motor  system 
is  not  complete.  The  paralysis  of  the  afferent  nerves  in  advanced  aconite- 
poisoning,  by  shutting  off  from  the  vaso-motor  centre  the  impulses  which 
normally  reach  it  from  without,  must  certainly  affect  the  general  tone  of 
the  vessels,  a  reasoning  which  finds  strong  confirmation  in  the  fact  asserted 
by  Boehm  and  Wartmann,  that  there  is  a  stage  in  aconite-poisoning  in 
which  galvanization  of  a  sensitive  nerve  does  not  produce  rise  of  the  arte- 
rial pressure,  which,  however,  is  developed  at  once  when  the  vaso-motor 
centres  in  the  medulla  are  stimulated. 

S.  A.  Matthews  and  Cash  and  Dunstan  affirm  that  the  first  action 
of  the  drug  upon  the  vaso-motor  centre  is  as  a  stimulant,  but  we  have 
not  been  able  to  find  in  their  papers  any  sufficient  proof  of  this,  and  do 
not  believe  that  the  conclusion  is  probable.  It  is  likely  that  in  the 
advanced  stages  of  the  poisoning  the  vaso-motor  centre  is  depressed  or 
paralyzed,  though  this  has  not  been  positively  proved.  The  best  evi- 
dence is  that  furnished  by  Cash  and  Dunstan, — namely,  that  there  is  a 
period  in  which  mechanical  asphyxia  ceases  to  elevate  the  pressure. 

That  the  efferent  vaso-motor  apparatus  is  not  paralyzed  is  shown  by 
the  facts  that  in  advanced  poisoning  galvanization  of  the  sympathetics  in 
the  neck  causes  contraction  of  the  vessels  (Nunneley14),  and  that  the 
splanchnics  retain  almost  to  the  last  their  functional  activity. 

Temperature. — In  the  very  beginning  of  aconite-poisoning  the  bodily 
temperature  may  rise  slightly,  but  in  severe  poisoning  a  very  pronounced 
fall  occurs.  The  reduction  of  the  bodily  heat  is  probably  caused  by  an 
increase  of  heat-dissipation.  If  vaso-motor  paralysis  occurs  in  aconite- 
poisoning  it  will  account  for  this  loss  of  heat.  Further,  it  is  entirely 
possible  that  aconite,  without  producing  vaso-motor  paralysis,  may,  by 
destroying  the  conducting  power  of  the  afferent  nerves,  put  an  end  to 
the  automatic  relation  between  heat-production  and  heat-dissipation.  In 
accord  with  this  is  the  observation  of  Brunton  and  Cash,15  that  in  animals 
exposed  to  a  high  temperature,  aconite,  far  from  depressing  the  tem- 
perature, favors  its  increase,  while  when  the  animal  is  exposed  to  cold, 
aconite  accelerates  the  fall  of  the  bodily  heat  remarkably  (confirmed  by 
Cash  and  Dunstan). 

SUMMARY. — Locally,  aconite  is  slightly  irritant  at  first  and  subse- 
quently paralyzant  especially  to  the  sensory  nerves.  It  yields  its  active 
principle  rapidly  to  absorption.  Aconite  has  little  direct  action  upon 


382  GENERAL  REMEDIES. 

the  cerebrum,  unless  it  be  upon  the  perceptive  centres  of  general  sensi- 
bility, concerning  -which  there  is  still  dispute.  It  is  asserted  by  some 
authorities  that  the  small  dose  stimulates  respiration,  but  this  has  not 
been  proved.  In  toxic  dose  it  acts  as  a  powerful  depressant  to  the  re- 
spiratory centres,  and  usually  kills  by  centric  paralytic  arrest  of  respira- 
tion. It  also  paralyzes  the  peripheral  fibres  of  the  vagus  in  the  lungs, 
and  thereby  notably  affects  respiratory  rhythm.  Its  action  upon  the 
spinal  cord  remains  uncertain,  some  authorities  believing  that  it  pri- 
marily stimulates  the  motor  side  of  the  cord,  and  very  late  in  the  poi- 
soning causes  centric  motor  depression.  Its  dominant  influence,  so  far 
as  the  nervous  system  is  concerned,  is,  however,  upon  the  sensory 
nerves,  affecting  primarily  their  peripheral  filaments  and  involving 
later  their  trunks.  It  has  also  some,  but  a  much  less  powerful,  depres- 
sive action  upon  the  motor  nerves.  According  to  some  authorities, 
the  stage  of  nerve-paralysis  is  preceded  by  one  of  nerve-stimulation, 
but  this  is  extremely  doubtful. 

Aconite  reduces  very  markedly  the  rate  of  the  pulse  and  the  arte- 
rial pressure,  the  primary  stage  of  slow  pulse  being  followed  by  one 
of  rapid  irregular  pulse,  with  very  fluctuating  but  still  low  press- 
ure. The  chief  cause  of  the  slow  pulse  is  stimulation  of  the  vagal 
nerve  ( aconitine,  benzaconine) ,  which  is  followed,  when  the  rapid  pulse 
comes  on,  by  depression  of  the  peripheral  vagi.  The  rapid  pulse  is  in 
part  due  to  the  withdrawal  of  inhibition,  and  probably  also  in  part  to 
a  direct  action  of  aconitine  upon  the  muscle-irritability.  Aconitine 
appears  primarily  not  to  affect  the  muscular  strength  of  the  heart,  but 
on  account  of  the  depressing  influence  of  the  benzaconine  upon  the 
muscle  the  cardiac  force  is  weakened  by  aconite  from  the  beginning. 

The  action  of  the  drug  upon  the  vaso-motor  system  is  not  estab- 
lished ;  several  recent  observers  affirm  that  the  first  action  of  the  drug 
upon  the  vaso-motor  centre  is  stimulation,  which  seems  to  us  to  be 
unproved  and  improbable;  in  the  advanced  stages  of  the  poisoning 
the  vaso-motor  centre  is  probably  depressed  or  paralyzed,  but  even 
concerning  this  our  knowledge  is  uncertain.  The  efferent  vaso-motor 
nerves  are  not  affected. 

The  bodily  temperature  is  reduced  by  aconite  by  an  increase  of 
heat-dissipation,  and  perhaps  also  by  an  action  on  the  thermo-genetic 
nervous  system.  On  the  glandular  system  of  the  body,  except  that  of 
the  skin,  aconite  has  little  or  no  influence. 

THERAPEUTICS. — The  general  indication  for  the  use  of  aconite  is  to 
lower  arterial  action,  but  the  selection  of  this  drug  among  other  cardiac 
depressants  for  this  purpose  should  be  governed  by  certain  definite  prin- 
ciples, depending  upon  the  known  peculiarities  of  its  action.  When  the 
high  arterial  pressure  is  chiefly  cardiac  in  origin,  it  is  the  best  drug  of  its 
class,  having  in  therapeutic  dose  little  or  no  influence  upon  the  system 
other  than  upon  the  heart,  and  producing  no  disturbance  of  gastric  or 
intestinal  digestion.  Further,  aconite  has  a  certain  permanence  of  action 
not  equal  to  that  of  digitalis  but  greater  than  that  of  the  other  car- 
diac depressants.  No  cases  or  reports  of  cases  of  cumulative  effects 
parallel  to  those  caused  by  digitalis  have  come  under  our  notice,  but 
when  small  doses  are  given  continuously  there  is  a  progressive  increase 
of  effect.  In  cases  of  cardiac  hypertrophy,  or  when  there  is  in  valvular 
disease  excessive  compensation,  aconite  is  the  best  remedy  that  we  have. 


CARDIAC   DEPRESSANTS.  383 

Given  in  doses  of  the  tincture,  from  two  to  five  minims  three  times  a 
day,  it  acts  steadily  and  persistently.  When  the  administration  is  free, 
the  effect  should  always  be  watched  carefully  and  the-  dose  lessened 
pro  re  nata. 

On  the  other  hand,  when  a  sudden,  very  powerful  influence  to  meet 
an  emergency  is  desired,  and  especially  when  it  is  necessary  if  possible 
to  produce  wide-spread  vaso-motor  weakness  and  consequent  relaxation 
of  the  blood-vessels,  aconite  should  not  be  employed.  The  overdose  is 
more  apt  to  produce  serious  results  than  is  the  overdose  of  veratrum 
viride,  and  the  effect  of  it  upon  the  blood-vessels  is  far  less  than  is  that  of 
veratrum  viride. 

In  the  forming  stage  of  sthenic  pneumonia  aconite  cannot  be  substi- 
tuted with  any  justification  for  veratrum  viride.  On  the  other  hand, 
in  irritative  fevers,  as  the  ephemera  of  childhood  from  gastro-intestinal 
irritation  or  other  cause,  aconite  in  moderate  dose  often  acts  most  hap- 
pily. Especially  is  it  useful  in  combination  with  other  drugs  which  have 
a  tendency  to  increase  the  secretion  from  the  skin,  when  it  is  desired  to 
produce  free  sweating.  If  only  a  moderate  but  continuous  skin  effect  is 
desired,  aconite  may  be  given  with  neutral  mixture  ;  to  it  may  be  added, 
if  circumstances  favor,  antipyrin.  When  it  is  desired,  as  in  acute  mus- 
cular rheumatism  or  in  a  forming  grippe,  to  produce  very  free  sweating, 
a  combination  of  aconite,  pilocarpine,  and  antipyrin  is  very  effective.  In 
a  urethral  fever  due  to  the  passage  of  the  catheter  or  bougie,  aconite 
often  acts  most  happily. 

A  second  indication  which  aconite  might  be  used  to  fulfil  is  to  allay 
spasm.  As,  however,  its  influence  upon  the  motor  centres  and  nerves  is 
much  less  than  upon  the  sensitive  centres  and  nerves  and  upon  the  heart, 
the  indication  is  better  met  by  other  remedies. 

A  third  indication,  which  it  would  seem  from  its  known  physiological 
action  that  aconite  should  meet,  is  to  relieve  over-excitation  of  the  sensitive 
nerves.  Although  aconite  was  formerly  very  much  used  for  the  relief  of 
pains  which  were  called  neuralgic,  and  is  sometimes  useful  when  an  acute 
neuritis  has  followed  exposure  to  cold,  and  is  of  a  rheumatic  type,  it  is 
rarely  of  real  service  even  as  a  local  remedy,  and  is  of  no  value  whatso- 
ever in  such  diseases  as  migraine  when  the  pain  is  of  centric  origin. 

Given  in  full  doses  in  the  reflex  vomiting  of  pregnancy,  aconite  is  often 
advantageous,  acting  probably  by  benumbing  the  sensory  reflex  centres, 
or  possibly  the  afferent  peripheral  gastric  nerves.  We  have  noticed  that 
relief  lasts  only  so  long  as  decided  constitutional  effects  from  the  drug  are 
apparent. 

TOXICOLOGY. — Aconite  is  an  exceedingly  powerful  poison  ;  one- 
twelfth  of  a  grain  of  the  crystallized  aconitine  is,  according  to  Duquesnel, 
sufficient  to  kill  a  rabbit  in  a  short  time.  Five  grains  of  an  extract  and 
eighty  minims  of  a  tincture  are  said  to  have  caused  death  (Reichert18). 
The  symptoms  usually  come  on  in  a  very  few  minutes.  In  the  shortest 
case  we  have  met  with,  death  occurred  in  thirty  minutes.  The  average 


384  GENERAL   REMEDIES. 

time  of  death  (Reichert)  is  three  and  a  third  hours,  the  longest  recorded 
case  being  five  and  a  half  hours. 

The  aconitines  of  commerce  vary  inordinately  in  strength,  so  that  while  one- 
sixteenth  of  a  grain  (prepared  by  Petit,*  of  Paris)  caused  the  death  of  Carl  Meyer 
in  five  hours,  and  a  quarter  of  a  milligramme  is  said  to  have  produced  violent  poison- 
ing, several  grains  of  the  impure  article  so  largely  sold  have  been  recovered  from. 
The  symptoms  have  been  in  general  those  of  aconite-poisoning,  but  excessively 
violent  pains  and  convulsions  have  been  very  marked  features  of  some  of  the  cases. 
(For  discussion  of  aconitine-poisoning,  see  Thomas  Stevenson,17  M.  Jules  Bassott,13 
also  six  cases,  Lhote  and  Vibert.19) 

The  only  diagnostic  symptom  of  aconite-poisoning  is  the  peculiar 
tingling,  which  is  probably  always  present,  though  in  suicidal  cases  the 
patient  may  refuse  to  reveal  it,  or  in  advanced  poisoning  unconsciousness 
may  prevent  its  being  told.  The  presence  in  any  case  known  to  be  one 
of  poisoning  of  absolute  prostration  with  almost  complete  failure  of  the 
pulse,  great  muscular  relaxation,  and  other  symptoms  of  collapse,  with- 
out vomiting,  purging,  or  any  disorder  of  the  pupil  or  other  toxic  mani- 
festations, is  sufficient  for  a  working  diagnosis. 

The  first  indication  for  treatment  in  aconite-poisoning  is  evacuation  of 
the  stomach  ;  as  emetics  usually  fail,  on  account  of  the  local  gastric  anaes- 
thesia, the  stomach-pump  may  often  be  used,  but  the  danger  of  causing 
fatal  collapse  in  extreme  cases  must  not  be  overlooked.  Tannic  acid  may 
be  administered  as  an  imperfect  antidote.  Hot  concentrated  alcoholic 
stimulants  should  be  freely  given  ;  strychnine,  atropine,  and  digitalis  f 

*  In  the  researches  of  Anrep,  Duquesnel's  crystallized  aconitine  was  nearly  twice  as 
strong  as  a  German  alkaloid  used  by  him,  which  in  turn  was  much  stronger  than  an  Eng- 
lish article.  Plugge  found  Petit's  aconitine  eight  times  as  strong  as  that  of  E.  Merck. 
Langgaard  found  an  alkaloid  prepared  from  A.  japonicum  exceedingly  powerful.  The 
best  discussions  of  the  relative  strength  of  these  alkaloids  that  we  know  of  may  be  found 
in  Schmidt's  Jahrb.,  ccii.  124,  and  in  Des  Aconils,  by  J.  V.  Laborde  and  H.  Duquesnel, 
Paris,  1883.  Lh6te  and  Vibert  (Annal.  d1  Hyg.  Publ.,  1892,  xxviii.)  assert  that  the  crystal- 
lized aconitine  of  Duquesnel  is  an  essential!}'  different  poison  from  the  amorphous  aconi- 
tine of  commerce  or  from  the  aconitine  sulphate  of  Merck.  The  latter  in  the  isolated 
frog's  heart  they  found  to  produce  gradual  progressive  enfeeblement,  whilst  the  Duquesnel 
aconitine  caused  primarily  great  increase  in  the  size  of  the  cardiac  pulsation,  with  periods 
of  ataxia,  followed  by  depression. 

fThe  original  discovery  of  J.  Milner  Fothergill  (Digitalis,  London,  1871,  6),  that 
digitalis  is  the  cardiac  antagonist  of  aconite,  has  been  abundantly  confirmed.  The  careful 
work  of  Matthews  and  of  Cash  and  Dunstan  has  demonstrated  that  it  is  benzaconine  which 
is  especially  antagonized  by  the  digitalin,  atropine  being  the  cardiac  antagonist  of  aco- 
nitine. Clinical  experience,  although  still  limited  in  extent,  strongly  corroborates  the  ex- 
perimental evidence  of  the  value  of  digitalis.  Successful  cases  may  be  found  in  Brit. 
Med.  Journ.,  Dec.  n,  1872  (fgi  Fleming's  tincture,  Tinct.  digitalis  lt\x  hypodermically)  ; 
Bost.  Med.  and  Surg.  Journ.,  Oct.  1879,  544  (fSiii  Tinct.  aconit.  rad.,  Tinct.  digitalis  mix 
hypodermically)  ;  Indian  Med.  Gaz.,  xvii.  323  (Aconitum  ferox  root  forty-eight  grains, 
Tinct.  digitalis  mxxv  hypodermically  and  f/>5  by  mouth)  ;  Phila.  Med.  Times,  xiii.  328  (a 
decoction  of  aconite,  amount  unknown,  Tinct.  digitalis  in  drachm  and  half-drachm  doses, 
by  mouth).  In  a  successful  case  treated  by  Elliot  (Lancet,  1878,  ii.  917)  amyl  nitrite 
freely  inhaled  seemed  to  do  great  good  :  a  fluidounce  of  a  concentrated  aconite  liniment 
was  thought  to  have  been  taken.  Ammonia  injections  were  unsuccessful  in  a  case  re- 
ported in  the  Australian  Med.Jotirn.,  1879,  i.  283.  G.  H.  Tuttle  (Boston  Med.  and  Surg. 
Journ.,  1891,  cxxv.)  has  reported  recovery  after  seven  and  a  half  drachms  of  the  tinct- 
ure, under  the  free  hypodermic  use  of  brandy  and  digitalis,  the  same  remedies  with 
tincture  of  nux  vomica  being  given  internally,  and  auxiliary  measures  used. 


CARDIAC   DEPRESSANTS.  385 

should  be  used  hypodermically  with  great  boldness,  tempered  with  cau- 
tion. Ammonia  may  be  injected  into  the  veins,  if  it  be  found  practicable. 
The  patient  must  be  kept  upon  the  back,  with  the  feet  a  little  higher  than 
the  head,  and  external  heat  be  used  freely  to  maintain  temperature.  La- 
borde  and  Duquesnel  affirm  that  in  the  lower  animals  death  after  a  usu- 
ally fatal  dose  of  aconitine  can  be  prevented  by  artificial  respiration  ;  and 
in  a  case  of  human  poisoning,  if  the  heart's  action  were  at  all  sustained, 
and  the  respiration  failing,  Sylvester's  method  or  forced  artificial  respira- 
tion might  be  resorted  to. 

ADMINISTRATION. — Aconite  is  never  used  in  substance.  Dose  of 
tincture  of  aconite  (TINCTURA  ACONITI — ten  per  cent.,  U.  S.),  three 
to  fifteen  minims  (o.  18-1.0  C.c. ),  repeated  every  one  to  three  hours 
pro  re  nata,  its  effects  being  always  watched.  Fleming1  s  tincture  is  a 
stronger  preparation  (ten  and  a  half  ounces  to  a  pint).  Dose  of  extract, 
one-quarter  to  three-quarters  of  a  grain  (0.016-0.049  Gm. );  of  fluid  ex- 
tract (FLUIDEXTRACTUM  ACONITI,  U.  S. ),  one  to  two  minims  (0.06- 
o.  1 2  C.  c. ) .  The  tincture  or  the  fluid  extract  of  aconite  is  very  frequently 
added  to  stimulating  and  anodyne  liniments. 

Owing  to  its  varying  purity  and  composition  and  its  extraordinary 
activity,  aconitine  should  rarely  be  used  in  practical  medicine.  The  dose 
of  the  official  ACONITINE  is  given  in  the  U.  S.  Pharmacopoeia  as  TSTS  grain 
(0.00015  Gm. ). 

ACIDUM    HYDROCYANICUM— HYDROCYANIC   ACID. 

Pure  hydrocyanic  acid  is  a  colorless,  transparent,  volatile,  inflamma- 
ble liquid,  giving  rise  to  giddiness  and  headache  when  smelled,  and 
having,  it  is  said,  a  burning,  bitter  taste.  So  poisonous  is  it  that  when 
inhaled  it  causes  death,  and  it  must  be  handled  with  the  greatest  cau- 
tion :  smelling  and  tasting  it  are  excessively  dangerous  proceedings.  It 
is,  indeed,  an  imperative  rule  that  no  one  should  experiment  with  an- 
hydrous prussic  acid  alone,  or  under  any  circumstances  in  summer,  or  in 
a  warm  room,  or  in  an  apartment  whose  open  windows  and  doors  do  not 
admit  of  a  free  draught  of  air.  The  chemist  Scheele,  the  discoverer  of 
prussic  acid,  is  believed  to  have  been  killed  by  the  inhalation  of  the  fumes 
of  this  material,  whose  poisonous  properties  were  first  pointed  out  by 
the  Berlin  apothecary  Schrader  in  1803.  The  anhydrous  acid  is  soluble 
in  water  and  in  alcohol,  but  is  never  kept  in  the  shops,  and  is  not  official. 

Hydrocyanic  acid  of  common  medical  parlance  is  the  official  Dilute 
Hydrocyanic  Acid  (ACIDUM  HYDROCYANICUM  DILUTUM,  U.  S. ),  a  color- 
less, watery  solution,  containing  two  per  cent,  of  the  anhydrous  acid.  Its 
odor  and  taste  are  the  familiar  ones  of  peach-kernels  and  bitter  almonds  ; 
its  reaction  is  faintly  acid.  As  it  has  a  great  tendency  to  undergo  spon- 
taneous decomposition,  especially  under  the  influence  of  light,  it  should 
be  kept  in  well-stopped,  dark-colored  bottles. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Absorption  and  Elimina- 
tion.— Hydrocyanic  acid  appears  to  be  free  from  irritant  properties,  but 

25 


386  GENERAL   REMEDIES. 

is  a  universal  depressant  poison,  capable,  when  in  sufficient  amount,  of 
paralyzing  all  higher  tissues,  and  having,  when  applied  locally,  an  espe- 
cially powerful  influence  upon  sensory  nerve-endings.  It  is  absorbed 
with  almost  instantaneous  rapidity  through  all  mucous  membranes.  Con- 
cerning its  fate  in  the  body  we  have  no  knowledge  except  that  it  is 
either  destroyed  or  eliminated  with  the  greatest  rapidity,  so  that  its 
action  is  extremely  fugacious. 

General  Action. — The  symptoms  produced  by  prussic  acid  in  man 
are  so  rapid  in  development  and  course  that  usually  the  patient  is  dead 
or  convalescent  before  seen  by  the  physician.  The  ordinary  therapeutic 
dose  produces  no  distinct  manifestations  ;  after  the  toxic  dose  the  symp- 
toms come  on  suddenly.  In  a  moment  or  two  the  individual  falls  to  the 
ground  insensible  and  convulsed,  the  respirations  arrested  or  occurring 
at  long  intervals,  the  eyes  salient,  the  pupil  dilated,  the  mouth  covered 
with  bloody  froth.  If  the  dose  be  sufficiently  large,  death  may  occur  in 
three  or  four  minutes  ;  if  less  has  been  taken,  deep  insensibility,  tetanic 
or  clonic  convulsions,  dilated  pupils,  a  bloated  countenance,  cyanosed 
surface,  set  jaws,  and  irregular  respiration  constitute  the  chief  symp- 
toms. The  breathing  is  mostly  convulsive,  with  deep,  forcible  expira- 
tions, but  in  some  cases  it  has  been  stertorous.  Death  results  from  as- 
phyxia. After  small  toxic  but  not  lethal  doses  of  prussic  acid,  giddiness, 
lightness  of  the  head,  nausea,  a  quick  pulse,  and  muscular  weakness  are 
the  chief  symptoms. 

After  a  full  dose  of  the  strong  anhydrous  prussic  acid,  the  lower  animal  gasps  once 
or  twice,  and  then  instantly  falls  in  a  tetanic  or  clonic  convulsion,  or  else  drops  mo- 
tionless and  powerless  upon  its  side,  heart  and  lungs  ceasing  almost  at  once.  After 
a  smaller  toxic  dose  the  signs  of  asphyxia  at  once  manifest  themselves,  and  grow 
more  and  more  intense,  until  they  end  in  total  arrest  of  respiration.  The  heart 
beats  irregularly,  often  at  first  slowly  and  strongly,  with  intervals  of  suspension  of 
movement,  but  always  becoming  weaker  and  more  rapid  in  its  action,  until,  after 
the  breathing  has  ceased,  its  efforts  gradually  die  away.  Ordinarily,  three  distinct 
stages  are  apparent :  a  first,  very  brief  one,  of  difficult  respiration,  slow  cardiac 
action,  and  disturbed  cerebration  ;  a  second,  convulsive  stage,  with  dilated  pupils, 
violent  convulsions,  unconsciousness,  loud  cries,  vomiting,  often  spasmodic  urina- 
tion and  defecation,  erections,  etc. ;  and  a  third  period,  of  asphyxia,  collapse,  and 
paralysis,  sometimes  interrupted  by  partial  or  even  general  spasms. 

The  slow  form  of  the  poisoning  follows  the  exhibition  of  the  poison  in  an  amount 
just  sufficient  to  kill.  After  the  ingestion  of  such  a  dose,  no  phenomena  are  offered 
for  some  seconds ;  then  the  breathing  becomes  labored  and  the  pulse  slow  and  full. 
The  animal  perhaps  cries  out,  and  muscular  tremblings  rapidly  grow  into  clonic 
and  tonic  convulsions,  which  continue  at  intervals  until  the  third  stage — that  of  col- 
lapse— is  developed.  When  the  third  stage  is  developed,  the  anaesthesia  is  marked, 
affecting  first  the  hind  legs,  but  finally  spreading  to  all  parts  of  the  body,  and  even 
being  complete  in  the  widely  dilated  pupil.  Death  finally  results  from  failure  of 
respiration.  Recovery  may  occur  even  after  the  conjunctiva  has  lost  its  sensibility  ; 
the  return  to  life  by  a  subsidence  of  the  symptoms  is  usually  rapid,  so  that  generally 
in  from  one-half  to  three-quarters  of  an  hour  the  animal  will  be  eating  as  though 
nothing  had  happened.  Coullon,  however,  noted  persistence  of  paralysis,  in  some 
cases,  for  days. 


CARDIAC    DEPRESSANTS.  387 

Blood. — Prussic  acid  has  a  very  decided  influence  upon  the  blood, 
which  may  after  death  be  found  uniformly  of  a  bright  arterial  or  a  deep 
venous  hue. 

F.  B.  Vietz,1  E.  L.  Schubarth,2  J.  F.  Sobernheim,3  Coze,*  Claude  Bernard,  and 
others  all  affirm  that  when  an  animal  is  killed  abruptly  with  hydrocyanic  acid  the 
blood  in  the  veins  and  right  heart  is  of  a  bright  arterial  hue.  In  1844,  how- 
ever, J.  R.  Bischoff  *  affirmed  that  in  man  and  in  mammals  killed  with  prussic 
acid  nothing  could  be  found  but  dark  venous  blood  in  either  artery  or  vein,  an  ob- 
servation which  has  been  since  confirmed.  The  explanation  of  these  discrepancies 
was  first  given  by  W.  Preyer,6  and  subsequently  confirmed  by  Carl  Gaethgens  ; T 
directly  after  the  administration  of  the  poison,  in  the  mammal  the  venous  blood  be- 
comes almost  immediately  of  a  bright  arterial  hue,  which,  however,  rapidly  darkens 
until  all  the  blood  of  the  body  is  venous.  If  the  mammal  dies  suddenly  from  car- 
diac paralysis  during  the  first  stage  of  the  poisoning,  this  excessive  arterialization 
may  be  found  after  death,  and  in  cold-blooded  animals,  the  bright  color  persists 
for  many  hours  (Preyer).  If,  however,  life  is  more  prolonged,  the  blood  grows 
dark. 

According  to  Gaethgens,  the  scarlet  venous  blood  of  the  first  stage  of  the 
poisoning  shows  clearly  the  absorption  bands  of  oxyhaemoglobin  under  the  spec- 
troscope, whilst  Preyer  has  demonstrated  that  the  dark  blood  of  the  advanced 
stages  of  the  poisoning  gives  only  the  lines  of  reduced  haemoglobin. 

There  has  been  much  discussion  as  to  the  cause  of  these  changes  in  the  blood. 
Hoppe-Seyler  believes  that  the  scarlet  venous  blood  of  the  first  stage  of  the  poison- 
ing is  due  to  the  suspension  of  the  power  of  the  red  blood-corpuscles  to  yield  up 
their  oxygen.  Carl  Gaethgens  determined  that  during  this  first  stage  there  is  a 
limited  elimination  of  both  carbonic  acid  and  oxygen  from  the  lungs.  At  the  same 
time  the  percentage  of  carbonic  acid  in  the  expired  air  is  less,  and  that  of  oxygen  is 
greater,  than  in  the  normal  air,  showing  that  in  some  way  the  conversion  of  oxygen 
into  carbonic  acid  is  interfered  with.  It  is  clear  that  during  the  first  stage  of 
prussic  acid  poisoning  oxidation  is  arrested.  That  this  arrest  of  oxidation  is  due, 
as  believed  by  Hoppe-Seyler,  to  the  action  of  the  poison  upon  the  red  blood-cor- 
puscles seems  to  us  improbable,  since  it  has  been  proved  by  Gaethgens  that  when 
the  experiments  are  prolonged  there  comes  a  time  when  more  than  the  normal 
amount  of  carbonic  acid  is  eliminated, — a  fact  in  accord  with  the  excessive  carboni- 
zation of  the  blood  which  occurs  in  the  later  stages  of  protracted  hydrocyanic  acid 
poisoning.  In  the  advanced  stages  of  the  poisoning  the  red  corpuscles  must,  there- 
fore, be  functionally  very  active. 

As  first  discovered  by  Hoppe-Seyler,8  and  afterwards  confirmed  by  Preyer, 
when  hydrocyanic  acid  is  added  to  blood  outside  of  the  body  there  is  produced  a 
new  substance  giving  rise  to  new  spectroscopic  lines  and  without  ozonizing  power, 
the  so-called  cyanohesmoglobin.  It  has  been  determined  by  Schonbein  that  hydro- 
cyanic acid  destroys  the  ozonizing  power  of  living  vegetables,  such  as  roots,  fungi, 
etc. ,  and  also  of  blood  to  which  it  is  added  outside  of  the  body.  In  regard  to  the 
latter  fact  some  confirmation  has  been  afforded  by  Harley,  who  found  that  the  dark 
blood  taken  forty-eight  hours  after  death  from  the  subject  of  prussic  acid  poisoning, 
shaken  with  air,  and  allowed  to  stand,  yielded  gas  containing  about  twenty  per 
cent,  of  oxygen,  eighty  of  nitrogen,  and  no  carbonic  acid.  It  is  proved  that  the 
dark  blood  of  prussic  acid  poisoning,  shaken  with  the  air,  assumes  the  red  arterial 
hue,  and  Lecorche"  and  Meuriot9  have  shown  that  artificial  respiration  will  produce 
the  same  result  in  the  poisoned  animal.  On  the  other  hand,  it  has  been  spectro- 
scopically  proved  that  there  is  no  cyanohaemoglobin  in  the  blood  of  the  poisoned 
animal,  the  haemoglobin  existing  in  the  blood  either  as  haemoglobin  or  oxyhaemo- 
globin (Preyer,  Laschkewitsch,10  Hiller  and  Wagner11). 


388  GENERAL    REMEDIES. 

The  facts  just  epitomized  would  seem  at  first  sight  very  strong  evi- 
dence of  the  correctness  of  the  theory  of  Hoppe-Seyler,  that  hydrocyanic 
acid  in  the  first  stage  of  the  poisoning  paralyzes  the  ozonizing  power  of 
the  red  blood-corpuscles  ;  but  it  seems  very  difficult  to  see  how  a  sub- 
stance should  in  the  first  stage  of  poisoning  paralyze  the  ozonizing  power 
of  the  red  blood-corpuscles  and  in  the  next  stimulate  such  power  so  that 
the  blood  should  become  dark  and  loaded  with  carbonic  acid.  Further, 
it  has  been  shown  by  Preyer  that  the  excessive  oxygenation  and  the  sub- 
sequent excessive  carbonization  of  the  blood  are  not  peculiar  to  hydro- 
cyanic acid  poisoning,  but  are  equally  present  after  the  exhibition  of  sul- 
phuretted hydrogen,  and  even  after  mechanical  closure  of  the  mouth  and 
nose.  It  is  possible  that  a  heightened  arterial  pressure  producing  an  in- 
creased rapidity  of  circulation  may  cause  the  blood  to  pass  too  quickly 
through  the  capillaries  to  allow  time  for  the  usual  changes  ;  but  this  has 
not  been  proved,  and  at  present  it  must  be  acknowledged  that  we  are 
ignorant  as  to  the  immediate  cause  of  the  blood-changes  in  these  cases. 

Alterations  in  the  form  of  the  corpuscles  of  the  blood  have  been  sug- 
gested as  the  cause  of  the  changes  of  the  color,  Ernst  Geinitz  having 
found  that  both  in  the  frog  and  in  the  mammal  prussic  acid  distorts  the 
blood-corpuscles.  On  the  other  hand,  in  the  observations  of  Preyer, 
although  such  alteration  of  the  blood-corpuscles  could  be  produced  in 
mammalian  blood  outside  of  the  body,  yet  in  blood  drawn  immediately 
after  death  from  prussic  acid  the  corpuscles  offered  their  usual  character  ; 
a  fact  confirmed  by  Hiinef eld. 12  * 

Whatever  may  be  the  cause  of  the  changes  in  the  blood,  the  experi- 
ments of  Lewisson 13  would  appear  to  prove  that  the  action  of  the  poison 
on  the  nervous  system  is  a  direct  one,  and  not  due  to  these  changes  in 
the  vital  fluid,  for  the  observer  mentioned  found  that  prussic  acid  acted 
upon  the  bloodless  ' '  salt  frog' '  as  upon  the  normal  batrachian. 

Action  on  the  Heart. — The  action  of  hydrocyanic  acid  upon  the  heart 
varies  according  to  the  dose.  In  sufficient  amount  and  concentration  it 
produces  instantaneous  diastolic  arrest,  which  is  either  permanent  or 
reoccurs  after  a  few  slow  feeble  beats  (Preyer,  and  Lecorch6  and  Meuriot). 
As  early  as  1826  Krimer  found  that  prussic  acid  placed  directly  upon  the 
heart  of  the  frog  produces  arrest  of  its  beat  and  loss  of  its  muscular  irri- 
tability. Preyer  has  confirmed  this,  and  it  would  seem  to  be  proved  that 
the  cardiac  arrest  spoken  of  above  is  due  to  a  direct  action  upon  the 

*  According  to  E.  Ray  Lankester  (Pftiiger's  Archiv,  1869,  492),  when  blood  is  shaken 
with  cyanogen  gas,  and  allowed  to  stand  for  two  or  three  hours,  the  spectrum-changes 
are  exactly  the  same  as  after  similar  treatment  of  blood  with  CO.  The  compound  of 
cyanogen  and  hsmatin  (Cy,Hb)  offers  not  only  the  identical  spectrum  of  CO,Hb,  but 
also,  like  the  latter,  is  unaffected  by  reducing  agents.  After  the  blood  stands  awhile,  ac- 
cording to  Lankester,  the  spectrum  of  hydrocyanic  acid  (H,CN)  becomes  visible  in  it, 
and  the  Cy,Hb  undergoes  conversion  into  the  cyanohaemoglobin  (Cy,Hb)  of  Hoppe- 
Seyler. 

Any  one  desirous  of  investigating  this  subject  more  deeply  than  can  be  done  in  a 
work  like  the  present  should  consult  especially  the  papers  by  Hoppe-Seyler  (  Virchow^s 
Archiv,  xxxviii.,  and  scattered  through  the  Med.-chem.  Unterstichungen),  by  Harley 
(Lond.  Phil.  Trans..  1865,  706),  and  by  Preyer  (Pflilger's  Archiv,  1868,  395). 


CARDIAC   DEPRESSANTS.  389 

heart-muscle  or  its  contained  ganglia,  yet  that  after  cardiac  death  from 
prussic  acid  the  heart  responds  to  galvanism. 

The  cardiac  results  of  the  exhibition  of  small  non-toxic  doses  are, 
according  to  Preyer,  simply  slowing  of  the  heart's  action. 

Preyer  and  Laschkewitsch  agree  as  to  the  action  of  large,  but  not 
enormous,  doses.  At  first  there  is  a  sudden  prolonged  diastolic  arrest 
of  the  heart,  followed  by  an  augmentation  in  the  rapidity  of  the  cardiac 
action,  and  after  this  a  diminution  of  the  rate, — to  the  normal  number 
in  cases  of  recovery,  to  cardiac  stand-still  in  cases  of  death.  Both 
Preyer  *  and  Laschkewitsch  found  that  after  section  of  the  vagi  the  pri- 
mary diastolic  arrest  of  the  heart  did  not  occur.  Jos.  Lazarski "  has  also 
found  that  the  slowing  of  the  pulse  by  moderate  doses  of  hydrocyanic 
acid  is  prevented  by  previous  section  of  the  vagi.  It  would  seem,  there- 
fore, proved  that  small  doses  of  prussic  acid  stimulate  the  cardiac  inhibi- 
tory nervous  centres.  Boehm  and  Knie 15  noted  that  large  doses  of  the 
acid  caused  slowing  of  the  pulse  whether  the  vagi  were  cut  or  not,  and 
in  this  have  been  confirmed  by  Lazarski.  This  slowing  would  seem  to 
be  due  to  a  direct  action  upon  the  muscle  or  the  intra-cardiac  ganglia, 
as  Lazarski  found  that  the  cardiac  accelerator  nerves  are  not  paralyzed. 

Moderate  doses  of  prussic  acid  seem  to  produce  a  primary  very  brief 
but  great  rise  in  the  arterial  pressure,  followed  by  a  fall  to  or  below  the 
normal.  This  primary  rise  has  been  noticed  by  Boehm  and  Knie,  by 
Wahl,16  by  Rossbach  and  Papitzky,17  and  by  Lazarski.  It  does  not  seem 
to  be  altogether  the  result  of  the  asphyxia  produced  by  the  acid,  as  it  is 
recorded  by  Boehm  and  Knie  as  occurring  when  artificial  respiration  was 
used,  and  Lazarski  has  confirmed  this.  All  observers  agree  that  it  is 
followed,  if  the  dose  of  the  poison  has  been  large  enough,  by  a  profound 
sinking  of  the  arterial  pressure.  Lazarski  found  that  galvanization  of  a 
sensitive  nerve  has  no  effect  at  this  time  upon  the  blood-pressure  :  so  that 
we  must  consider  that  hydrocyanic  acid  primarily  stimulates  very  briefly 
the  vaso-motor  system  directly  or  indirectly,  and  afterwards  paralyzes  it. 

Respiration. — Hydrocyanic  acid  acts  directly  upon  the  respiratory  cen- 
tres as  a  depressant,  so  that  in  poisoning  by  it  the  respiratory  movements  are 
lessened  from  the  beginning,  and  becoming  more  and  more  distant  finally 
cease  before  the  heart's  action  is  arrested. 

Preyer  found  that,  after  division  of  the  vagi,  normally  lethal  doses  did  not  kill, 
and  that  when  death  was  brought  about  by  the  exhibition  of  larger  doses  it  was  by 
cardiac  arrest.  From  this  he  deduces  the  conclusion  that  the  prime  respiratory 
action  of  the  poison  is  upon  the  peripheral  ends  of  the  vagi.  Preyer's  experiments 
have  been  partially  confirmed  by  Lecorch6  and  Meuriot  ;  but  Boehm  and  Knie 
have  in  a  series  of  experiments  found  that  section  of  the  vagus  has  no  influence 
upon  the  respiratory  action  of  the  poison,  and  in  this  have  been  confirmed  by  Jos. 
Lazarski.  Even  if  investigations  had  proved  the  correctness  of  Preyer's  experi- 
ments, his  conclusion  could  not  be  considered  established,  because  we  know  so 
imperfectly  the  normal  relations  of  the  pneumogastrics  to  respiration.  Moreover, 

*  Preyer  (loc.  cit.,  93)  has  also  noted  the  same  absence  in  curarized  animals  poisoned 
by  hydrocyanic  acid. 


390  GENERAL   REMEDIES. 

Joseph  Jones 18  found  that  while  to  kill  an  alligator  by  the  administration  of  prussic 
acid  required  a  considerable  length  of  time,  its  application  to  the  medulla  produced 
within  one  minute  a  most  powerful  expiration,  ending  in  permanent  contraction  of 
the  muscles  of  respiration  and  collapse  of  the  lung.  In  the  experiments  of  H.  Ha- 
yashi  and  K.  Muto"7  doses  of  15  milligrammes  per  kilogramme  of  potassium  cyanide 
caused  in  the  rabbit  fatal  paralysis  of  respiration  at  a  time  when  the  phrenic  and 
motor  nerves  were  still  excitable. 

Action  on  Muscles,  Nerves,  and  Nerve- Centres. — Kolliker19  has  found 
that  in  frogs  dead  of  prussic-acid  poisoning  both  nerve-trunks  and  muscles 
are  unexcitable,  or  that  the  muscles  respond  very  feebly  to  direct  stimulation. 

He  also  showed  that  protecting  the  nerve-trunks  by  tying  their  supplying 
artery  prevented  any  loss  of  function  in  them  when  the  animal  was  poisoned,  and 
that  the  conclusion  of  Stannius,20  that  prussic  acid  applied  locally  to  the  nerves  has 
no  effect  upon  them,  was  due  to  his  having  used  on  the  nerve  employed  for  com- 
parison a  fluid  almost  as  deadly  as  the  prussic  acid. 

The  experiments  of  Kolliker  are  in  agreement  with  those  of  Stannius, 
that  the  muscle  dies  very  much  more  quickly  in  the  solution  of  the  acid 
than  does  the  nerve,  losing  its  excitability  in  from  seven  to  eight  minutes. 

This  rapid  destruction  of  muscular  irritability  by  the  local  application  of  prussic 
acid  was,  we  believe,  first  noted  by  Coullon  in  1819.  Yet  it  is  most  probable  that 
when  given  internally  prussic  acid  acts  almost  as  rapidly  upon  the  nerve-trunks  as 
upon  the  muscles,  since  Kolliker  noted  that  in  some  cases  galvanization  of  the 
nerve  was  incapable  of  causing  contractions  in  the  tributary  muscles,  although  the 
latter  responded  feebly  to  direct  stimulation.  This  fact  has  been  experimentally 
corroborated  by  Funke.21 

Upon  the  peripheral  sensitive  nerves  prussic  acid,  if  in  sufficient  con- 
centration, acts  as  a  paralyzant. 

Kolliker  found  that  if  the  leg  of  a  strychnized  frog,  whose  heart  had  been  cut 
out  to  prevent  absorption,  was  put  in  a  four  per  cent,  solution  of  prussic  acid,  in 
a  very  short  time  irritation  of  the  immersed  skin  ceased  to  produce  convulsions. 

From  the  slowness  with  which,  in  Kolliker' s  experiments,  the  nerve- 
trunks  were  affected  in  frogs  poisoned  by  hydrocyanic  acid,  it  seems 
probable  that  he  is  correct  in  his  conclusion  that  in  these  batrachians 
the  poison  first  paralyzes  the  brain,  then  the  reflex  centres  of  the  spinal 
cord,  and  afterwards  the  motor  nerves.  But  we  have  not  met  with  any 
experimental  evidence  in  regard  to  the  order  in  which  prussic  acid  affects 
the  nervous  system. 

According  to  Kiedrowski*  (quoted  by  Preyer),  in  frogs  it  first  paralyzes  the 
gray,  then  the  white  substance  of  the  brain,  and  the  early  disappearance  of  reflex 

*  We  have,  unfortunately,  been  unable  to  obtain  access  to  the  original  paper  of  E  de 
Kiedrowski.  Even  Preyer  appears  to  know  it  only  in  abstract.  According  to  him,  it  was 
published  in  1858,  at  Breslau,  as  a  dissertation,  under  the  following  title  :  De  quibusdam 
experimentis  quibus  quantum  vim  habeat  acidum  hydrocyanicum  in  nervorum  systema 
cerebro-spinale  atque  in  musculos  systematis  vertebralis  probatur. 


CARDIAC   DEPRESSANTS.  391 

movements  is  not  due  to  spinal  palsy,  but  to  destruction  of  the  functional  power  of 
the  peripheral  afferent  nerves.  Preyer  also  states  that  the  conclusions  of  Kie- 
drowski  rested  upon  the  following  experimentally  proved  fact,  which,  if  accurate, 
seemingly  renders  them  logically  inevitable.  When  a  frog  is  poisoned  with  prussic 
acid,  and  afterwards  with  strychnine  in  properly  proportioned  doses,  there  is  a  stage 
at  which  slight  irritation  of  the  afferent  nerve-roots  causes  violent  general  tetanic 
spasms,  although  the  most  intense  peripheral  irritation  fails  to  elicit  response. 

It  is  a  question  of  interest  to  decide  as  to  the  cause  of  the  convul- 
sions in  poisoning  by  hydrocyanic  acid.  We  have  found  that  they  do 
not  occur  after  section  of  the  cord  in  parts  below  the  point  of  section, 
and  that  they  are  therefore  cerebral  in  origin.  It  is  probable  that  the 
convulsions  are  secondary,  asphyxial,  or  due  to  disturbance  of  circulation. 
Laschkewitsch,  who  opened  the  thorax  of  a  rabbit  so  as  to  expose  the 
heart,  maintained  artificial  respiration,  and  administered  prussic  acid  ; 
directly  after  arrest  of  the  heart  had  commenced  the  convulsions  came 
on  ;  also  in  the  earlier  observation  of  Coze,2"  the  convulsions  did  not  occur 
until  directly  after  the  arrest  of  the  circulation.  In  frogs  poisoned  with 
hydrocyanic  acid,  convulsions  do  not  take  place.  Preyer  states  that  after 
section  of  the  vagi  convulsions  do  not  generally  happen  in  mammals,  but 
if  artificial  respiration  be  performed  they  come  on. 

SUMMARY. — When  in  sufficient  concentration  hydrocyanic  acid  is 
a  powerful  depressant  poison  to  all  the  higher  tissues.  It  is  absorbed 
immediately,  and  acts  at  once,  but  so  fugaciously  that  its  influence  is 
over  in  a  few  minutes.  In  poisoning  by  it  death  usually  occurs  through 
centric  paralysis  of  the  respiration,  but  the  depression  of  the  heart's 
action  is  pronounced,  and  diastolic  cardiac  arrest  sometimes  takes 
place  simultaneously  with  or  even  before  cessation  of  breathing.  It 
first  stimulates,  then  paralyzes  the  vagi ;  it  first  stimulates,  afterwards 
paralyzes  the  vaso-motor  system.  Upon  the  nerve-centres  it  has  a 
most  pronounced  depressing  influence,  and  it  is  also  a  paralyzant  to 
the  nerve- trunks  and  to  the  muscles  themselves.  There  is  some  reason 
for  suspecting  that  after  the  small  toxic  dose  of  hydrocyanic  acid  the 
paralytic  stage  is  preceded  by  a  very  brief  stage  of  excitement,  with 
centric  increase  of  the  respiratory  activity,  rise  of  the  arterial  pressure 
(caused  by  an  influence  upon  the  vaso-motor  centres  and  perhaps  upon 
the  heart),  and  slowing  of  the  pulse  from  stimulation  of  the  cardiac  in- 
hibitory centres.  Outside  of  the  body  hydrocyanic  acid  attacks  the 
red  blood-corpuscles,  forming  a  new  compound,  cyanohaemoglobin ; 
but  the  occurrence  of  this  change  during  life  in  hydrocyanic  acid  poi- 
soning is  doubtful. 

THERAPEUTICS. — Our  knowledge  of  the  physiological  action  of 
prussic  acid  does  not  lead  to  a  belief  in  its  wide  applicability  to  the  relief 
of  disease,  and  we  think  that  clinical  experience  has  demonstrated  that  it 
is  of  little  value  except  in  meeting  three  indications  :  first,  to  allay  cough  ; 
second,  to  relieve  irritation  of  the  gastric  nerves  ;  third,  to  allay  irrita- 
tion of  the  peripheral  sensitive  nerves. 

Prussic  acid  has  been  used  very  largely  to  allay  cough,  either  itself  or 
in  the  form  of  potassium  cyanide.  Owing  to  the  extreme  fugaciousness 


392  GENERAL  REMEDIES. 

of  its  action,  it  is,  however,  of  very  little  real  value  for  this  purpose.  It 
is  not  probable  that  the  effect  of  any  therapeutic  dose  of  the  acid  lasts 
over  twenty  minutes,  or  of  the  cyanide  over  forty-five  minutes. 

There  can  be,  on  the  other  hand,  no  doubt  as  to  the  value  of  prussic 
acid  in  certain  stomachic  affections,  especially  nervous  vomiting  and  gas- 
tralgia.  When  the  pain  is  accompanied  by  decided  dyspeptic  symp- 
toms, the  remedy  will  sometimes  succeed,  but  more  often  fails.  Even 
in  the  most  favorable  cases  it  does  not  always  afford  relief ;  and  as  the 
relief  when  it  does  occur  is  immediate,  or  at  least  is  very  soon  apparent, 
it  is  useless  to  persist  long  in  the  exhibition  of  the  remedy.  In  these 
cases  its  action  is  probably  local,  as  it  certainly  is  when  the  acid  is  em- 
ployed to  relieve  itching  in  prurigo  and  other  cutaneous  diseases.  For 
this  purpose  it  is  used  as  a  wash  (one- half  to  one  fluidrachm  in  one  fluid- 
ounce)  ;  but  great  care  must  be  taken  to  avoid  constitutional  effects, 
especially  when  there  is  any  abrasion  of  the  skin.  Very  serious  results 
are  said  to  have  been  caused  by  its  absorption  when  carelessly  used  in 
skin  diseases. 

Prussic  acid  has  been  commended  as  an  arterial  sedative  ;  but  unless 
given  in  dangerous  doses  it  has  no  such  action. 

TOXICOLOGY. — The  symptoms  of  prussic  acid  poisoning  have  already 
been  mentioned  :  those  of  most  value  from  a  diagnostic  point  of  view 
are  the  sudden  occurrence  of  unconsciousness,  the  violent  convulsions, 
the  general  paralysis,  the  peculiar  character  of  the  breathing,  expira- 
tion being  prolonged  and  forced,  and  the  rapid  results.  The  odor  of 
prussic  acid  upon  the  breath  is  very  often,  but  by  no  means  always, 
present.  When  distinct,  it  is,  of  course,  of  great  diagnostic  value. 
Leaving  out  of  sight  the  cyanides,  the  only  poison  with  which  prussic 
acid  could  well  be  clinically  confounded  is  nitrobenzol.  The  distinc- 
tion is  often  very  difficult,  large  doses  of  the  latter  substance  killing 
almost  as  quickly  as  prussic  acid  and  inducing  analogous  symptoms. 
Caspar  advises  that  after  death  the  body  be  left  open,  exposed  to  the 
air,  as  the  odor  of  prussic  acid  disappears  rapidly,  while  that  of  nitro- 
benzol is  persistent.  The  diseases  with  which  the  poisoning  may  be 
confounded  most  readily  are  some  forms  of  apoplexie  foudroyante,  and 
sudden  failure  of  the  heart's  action.  The  diagnosis  may,  during  life, 
be  almost  impossible.  It  has  been  asserted  that  stertorous  breathing 
does  not  occur  in  prussic  acid  poisoning  ;  but  it  has  been  present  in 
several  reported  cases.*  An  autopsy,  however,  ought  generally  to  ena- 
ble the  physician  to  determine  whether  the  case  has  or  has  not  been  one 
of  prussic  acid  poisoning,  if  the  symptoms  during  life  are  known. 

A  curious  case  of  temporary  hemiopia,™  apparently  caused  by  the 
fumes  of  hydrocyanic  acid,  is  reported. 

The  period  at  which  death  may  occur  after  the  ingestion  of  the  poison 
is  set  down  by  Lonsdale  at  from  one  to  fifty-five  minutes  ;  but  a  case  has 

*  See  Taylor's  Medical  Jurisprudence,  Philadelphia,  1873,  363. 


CARDIAC   DEPRESSANTS.  393 

been  observed  by  Hilton  Fagge,24  in  which  the  fatal  result  was  put  off  for 
at  least  an  hour  and  a  quarter  after  the  ingestion  of  hydrocyanic  acid. 
After  death  the  body  often  presents  a  livid  surface,  bloated  countenance, 
fixed  glassy  eyes  with  dilated  pupils,  and  clinched  fingers  ;  sometimes  it 
offers  nothing  worthy  of  note  except  excessive  rigidity,  and  the  face  may 
be  very  pale.  When  opened,  the  odor  of  prussic  acid  is  generally,  but 
not  always,  emitted  ;  the  mucous  membrane  of  the  stomach  is  very  com- 
monly found  much  congested,  and  the  dark  or  cherry-colored  liquid 
blood  usually  everywhere  fills  up  the  veins.  The  heart  is  soft  and  flaccid. 

The  treatment  of  poisoning  by  prussic  acid  is  of  little  avail.  Of  the 
several  chemical  antidotes  which  have  been  proposed,  hydrogen  dioxide 
is  the  most  practicable.*  But  such  is  the  rapidity  of  absorption  that  the 
case  is  usually  terminated  before  the  antidote  can  be  obtained.  The 
asserted  physiological  antagonism  of  atropine  has  been  disproved  by 
Keen'25  and  by  Boehm  and  Knie.  The  stomach  should,  if  possible,  be 
emptied  or  washed  out  with  a  thirty  per  cent,  hydrogen  dioxide  solution  if 
at  hand,  and  the  hypodermic  use  of  atropine  and  strychnine  as  respiratory 
stimulants  might  be  tried  ;  the  inhalation  of  the  vapors  of  ammonia,  and 
the  free  exhibition  of  ammonia  by  the  mouth  and  by  injection  into  the 
veins,  may  be  practised.  Artificial  respiration  has  been  found  very  suc- 
cessful by  Preyer,  and  by  Boehm  and  Knie,  in  animals,  and  should  always 
be  assiduously  practised.  Next  to  it  in  importance  is  the  use  of  the  alter- 
nate cold  and  hot  douche,  about  a  half  of  a  small  bucketful  of  cold 
water  and  the  same  quantity  of  very  hot  (115°  F. )  water  being  dashed 
upon  the  chest  in  rapid  succession.  There  is  considerable  experimental 
evidence  to  show  that  the  sodium  hyposulphite  is  capable  of  following 
prussic  acid,  cyanides,  nitrobenzole,  and  other  nitrites  into  the  system 
and  there  decomposing  them,  but  we  know  of  no  case  in  which  the  antidote 
has  been  used  upon  man.  As,  however,  it  is  harmless  it  might  well  be 
given  hypodermically.  f 

ADMINISTRATION. — The  dose  of  the  dilute  prussic  acid  (  ACIDUM  HY- 
DROCYANICUM  DILUTUM,  U.  S.  )  is  one  to  three  drops  (0.06-0. 18  C.c. ). 

Potassiiim  Cyanide  (POTASSII  CYANIDUM,  U.  S. )  occurs  in  white, 
amorphous,  opaque  masses,  having  the  odor  of  prussic  acid  and  a  taste 
of  similar  character,  but  somewhat  alkaline.  It  is  deliquescent,  and 
readily  soluble  in  water. 

When  potassium  cyanide  is  taken  into  the  stomach,  the  acids  there 
present  convert  it  into  prussic  acid,  and  the  same  change  probably  occurs, 
although  more  slowly,  even  when  the  salt  is  injected  directly  into  the 
blood-vessels.  The  physiological,  therapeutical,  and  toxicological  prop- 
erties of  this  salt  are  similar  to  those  of  prussic  acid.  J  Death,  however, 

*  See  E.  Merck,  Merck's  Arch.,  1900,  ii.  94. 

t  See  S.  Lang,  A.  E.  P.  P.,  1895,  Bd.  xxxvi. ;  J.  F.  Heymans  and  P.  Masoin,  A.  I.  P., 
1897,  iii,  fasc.  i  and  2;  R.  Verbrugge,  A.  I.  P.,  v.,  fasc.  3  and  4;  and  J.  Meurice,  A.  I.  P., 
vii.,  fasc.  i  and  2. 

%  Poisoning  has  occurred  from  the  inhalation  of  the  vapors  of  the  cyanide  and  from 
absorption  through  the  hands  (Brit,  and  For.  Med.-Chir.  Rev.,  July,  1876,  231). 


394  GENERAL  REMEDIES. 

does  not  occur  so  soon  as  from  hydrocyanic  acid,  and  insensibility  is 
sometimes  not  manifested  for  several  minutes.  Five  grains  of  the  salt 
have  caused  death  but  fifty  grains  have  been  recovered  from.  (See  Mc- 
Kelway.28)  Dose  :  one-twelfth  to  one-tenth  of  a  grain  (0.005-0.006  Gm. ). 

Silver  Cyanide  (ARGENTI  CYANIDUM,  U.  S. )  is  a  white  insoluble  powder,  wnich 
is  used  solely  for  making  prussic  acid. 

Cyanogen  Gas  has  been  studied  physiologically  by  B.  Bunge.18  He  finds  that 
it  kills  by  paralyzing  the  centres  of  respiration,  but  that  it  is  less  powerful  in  its 
influence  than  is  hydrocyanic  acid,  and  causes  only  very  feeble  convulsions. 

Bitter  Almonds  (AMYGDALA  AMARA,  U.  S. )  yield  a  volatile  oil,  Oleum 
Amygdala  Amarce,  Oil  of  Bitter  Almonds  ;  of  a  yellowish  color,  bitter,  acrid  taste, 
with  a  strong  odor  of  prussic  acid.  This  volatile  oil  consists  of  benzoic  aldehyde 
contaminated  with  various  substances,  of  which  the  most  important,  prussic  acid, 
has  been  present  to  such  an  extent  that  two  drachms  of  the  commercial  oil  are  said 
to  have  caused  death  in  ten  minutes.  Very  properly,  under  the  name  of  Benzal- 
de/iydum,  U.  S.,  Benzaldehyde,  the  pure  benzoic  aldehyde,  produced  synthetically 
or  obtained  from  natural  oils,  has  been  recognized  in  the  last  edition  of  the  U.  S. 
Pharmacopoeia,  fhis  is  a  colorless,  strongly  refractive  liquid,  having  a  bitter  odor 
and  a  burning  taste.  The  official  oil  and  benzaldehyde  are  very  seldom  used  ex- 
cept as  flavoring  agents. 

VEGETABLE    ACIDS. 

Although  most  of  the  official  vegetable  acids  differ  so  much  from  the 
other  substances  considered  in  the  present  class  as  not  to  be  poisonous 
except  in  enormous  doses,  and  although  they  are  never  used  to  produce 
a  profound  impression  upon  the  circulation,  yet,  since  they  have,  or  at 
least  are  believed  to  have,  the  power  of  lowering  the  force  of  the  cardiac 
movements  to  some  extent,  and  since  they  are  so  commonly  believed  to 
have  a  tendency  to  depress  animal  temperature  as  to  be  usually  spoken 
of  as  refrigerants,  the  present  seems  to  us  a  fitting  place  for  their  con- 
sideration. In  experiments  made  by  W.  H.  Gaskell,1  similar  to  those 
described  in  the  article  on  digitalis  (see  page  300),  it  was  found  that 
while  alkalies  contracted  the  arterioles  of  the  frog,  acids  *  caused  a  dila- 
tation, probably  by  paralyzing  the  muscular  coats.  Acids  also  dimin- 
ished the  activity  and  power  of  the  frog's  heart. 

ACIDUM    TARTARICUM— TARTARIC   ACID.     U.S. 

Tartaric  acid  occurs  in  large,  hard,  transparent,  six-sided  prisms, 
which  are  pyro-electric  and  phosphorescent  when  rubbed  in  the  dark, 
are  nearly  free  from  odor,  have  a  very  sour  taste,  and  are  very  soluble  in 
water.  In  the  shops  the  acid  is  almost  always  kept  in  the  form  of 
powder.  Tartaric  acid  is  the  acid  of  the  grape,  and  occurs  in  grape- 
juice  as  potassium  bitartrate.  When  the  juice  undergoes  fermentation 
and  alcohol  is  developed,  the  acid  salt,  not  being  soluble  in  the  newly 

*  Lactic  acid,  however,  appears  to  have  been  the  only  one  used,  and  it  does  not  seem 
certain  that  the  results  of  experiments  would  be  the  same  with  all  acids,  as  is  stated  in 
Gaskell's  generalization. 


CARDIAC   DEPRESSANTS.  395 

formed  menstruum,  precipitates,  collecting  as  a  dark  mass  in  the  wine- 
casks,  whence  it  is  sent  into  commerce  under  the  name  of  argol  or  tartar. 
PHYSIOLOGICAL  ACTION. — In  powder  or  concentrated  solution  tar- 
taric  acid  is  a  very  decided  irritant,  capable  of  producing,  when  taken 
internally,  violent  cesophageal  and  gastric  burning,  vomiting,  and,  it  may 
be,  fatal  gastro- enteritis.* 

Mitscherlich  states  that  three  or  four  drachms  suffice  to  kill  a  rabbit,  the  evident 
symptoms  being  great  weakness  of  the  heart's  action,  difficult  and  slow  breathing, 
and  steadily  increasing  pains,  with  slight  convulsions  before  death.  According  to 
Devergie,  it  requires  nearly  half  an  ounce  to  kill  a  dog  when  given  by  the  stomach  ; 
but  Pommer  (quoted  by  Husemann)  asserts  that  one  gramme  (15.34  grains)  in- 
jected into  the  crural  vein  of  a  dog  will  produce  death. 

Concerning  the  action  of  therapeutic  doses  of  tartaric  acid  we  have  no  definite 
information.  General  clinical  experience,  in  accord  with  the  experiments  of  Bo- 
brick.t  who  found  that  very  large  doses  render  the  heart's  action  weaker  and  slower, 
indicates  that  the  drug  is  a  very  feeble  cardiac  depressant.  It  is  probably  partially 
burnt  up  in  the  body  and  partially  eliminated  by  the  kidneys.  W6hler,f  in  his  ex- 
periments, found  it  in  the  urine  in  the  form  of  calcium  tartrate,  while  Buchheim  f 
and  Piotrowski  t  could  find  only  a  very  small  percentage  of  the  ingested  acid  in  the 
urine,  and  conclude  that  it  is  mostly  destroyed  in  the  body.  Munch *  finds  that 
when  tartaric  acid  or  citric  acid  is  given  it  soon  appears  in  the  urine.  H.  Bence 
Jones  *  has  found  that  both  citric  acid  and  tartaric  acid  cause  a  pronounced  increase 
in  the  acidity  of  the  urine  of  persons  taking  them,  and  are  apt  also  to  give  rise  to 
the  presence  of  free  uric  acid  in  the  excretion.  Unfortunately,  Jones  did  not  attempt 
to  determine  whether  the  increased  acidity  was  or  was  not  due  to  the  presence  of 
the  vegetable  acid  in  the  urine. 

THERAPEUTICS. — Tartaric  acid  is  rarely  used  in  medicine,  citric  acid 
almost  always  being  preferred.  It  may,  however,  be  employed  whenever 
it  is  desired  to  render  the  urine  acid,  in  doses  of  ten  to  twenty  grains 
(0.6-1.3  Gm. ). 

TOXICOLOGY. — There  are,  we  believe,  but  three  fatal  cases  of  tartaric 
acid  poisoning  on  record  :  one  reported  by  Devergie,*  one  by  Taylor,4  in 
which  death  took  place  nine  days  after  the  ingestion  of  an  ounce  of  the 
poison  dissolved  in  half  a  pint  of  water,  and  one 5  in  which  half  an  ounce 
of  the  acid  was  supposed  to  have  been  taken.  The  treatment  of  tartaric 
acid  poisoning  consists  in  the  free  exhibition  of  magnesia,  of  lime,  of 
potassium  or  sodium  carbonate,  or  of  any  article,  such  as  soap,  contain- 
ing an  alkali  in  a  suitable  shape,  which  may  be  at  hand.  The  after-treat- 
ment is  that  of  toxic  gastro-enteritis. 

ACIDUM  CITRICUM— CITRIC  ACID.     U.  S. 

Citric  acid  is  the  acid  of  lemon- and  lime-juice.  It  occurs  in  rhom- 
boidal  prisms,  of  a  sour,  almost  corrosive,  taste,  extremely"  soluble  in  water. 

*  Case  reported  in  the  Brit.  Med.  Journ.,  for  June,  1893,  in  which  the  supposed  dose 
was  one  hundred  and  eighty  grains.  Symptoms :  diarrhoea,  violent  abdominal  pains 
becoming  more  and  more  marked,  followed  by  fever,  delirium,  and  death  on  the  seventh 
day.  At  the  autopsy  violent  inflammation  of  the  whole  of  the  gastro-intestinal  tract  was 
found. 

t  All  these  are  quoted  by  Husemann  (Die  Pflanzenstoffe}.  We  have  not  seen  the 
originals. 


396  GENERAL  REMEDIES. 

PHYSIOLOGICAL  ACTION. — Citric  acid  in  concentrated  form  is  actively 
irritant,  but,  according  to  Mitscherlich,  is  less  so  than  tartaric  acid,  since 
its  concentrated  solution  has  no  action  upon  the  sound  skin.  Serious 
poisoning  by  it  is  extremely  rare,  and  we  know  of  but  one  recorded  fatal 
case  (H.  Kionka).3 

Piotrovvski  (quoted  by  Husemann)  took,  in  six  hours,  thirty  grammes,  an 
hour  later  fifteen  grammes,  and  an  hour  later  thirty  grammes,  or  nearly  two 
ounces  and  a  half  in  all,  with  the  induction  of  no  more  serious  symptom  than 
vomiting. 

In  Kionka's  case,  a  girl  in  order  to  produce  abortion  took  an  unknown  quantity 
of  citric  acid,  and  was  brought  dying  into  the  hospital  with  the  only  clinical  record 
that  she  had  vomited  greatly.  Nine  thousand  four  hundred  and  fifty-two  grains  of 
citric  acid  were  collected  from  her  gastro-intestinal  tract.  Marked  evidences  of 
violent  gastritis  were  present,  with  gross  evidences  of  hepatic  degeneration.  In  the 
experiments  of  Maass 4  citric,  acetic,  and  tartaric  acid  were  found  to  have  very  little 
influence  on  frogs  unless  in  large  quantities. 

Hugo  Schulz l  states  that  citric  acid  is  an  active  antiseptic,  a  five  per 
cent,  solution  being  sufficient  to  preserve  small  pieces  of  meat  for  two 
weeks  ;  one  part  in  a  thousand  was  fatal  to  paramecia. 

THERAPEUTICS. — Lemon-juice  (Succus  LIMONIS,  U.  S. )  is  a  valuable 
remedy,  but  how  or  why  it  acts  is  at  present  entirely  unknown.  According 
to  the  analysis  of  H.  Bence  Jones,2  lemon-juice  contains  about  twenty-six 
grains  of  free  citric  acid  and  less  than  two  grains  of  potassium  citrate  to  the 
ounce,  but  neither  citric  acid  nor  any  of  its  known  salts  act  in  disease  as 
does  the  juice  of  the  fruit.  M.  Schmitt  found  lemon-juice  in  very  large 
dose  increases  the  flow  of  urine,  but  at  the  same  time  markedly  diminishes 
the  elimination  of  urea  and  of  acids.  The  chief  and  most  important  use 
of  lemon-juice  is  in  the  cure  and  prevention  of  scurvy.  During  the  dis- 
ease three  or  four  ounces  may  be  given  three  times  a  day.  As  a  prophy- 
lactic against  the  disease,  lemon-juice  is  simply  invaluable  ;  but  it  is 
absolutely  necessary  that  it  be  of  good  quality.  It  may  be  prepared  for 
long  voyages  in  one  or  two  ways :  first,  boil  the  juice  slightly,  strain, 
allow  to  cool,  pour  into  bottles  up  to  their  necks,  fill  the  vacant  space 
above  with  pure  olive  oil,  cork  tightly,  and  keep  the  bottle  upright ; 
second,  add  ten  per  cent,  of  brandy,  and  bottle  as  before.  In  acute 
rheumatism,  benefit  may  be  derived  from  the  free  use  of  lemon-juice,  as 
originally  proposed  by  Rees,  of  London.  One  or  two  ounces  of  it  may 
be  given  four  or  five  times  a  day  ;  but  it  is  certainly  less  efficacious  than 
the  alkalies.  In  catarrhal  jaundice  and  in  habitual  torpor  of  the  liver 
the  free  administration  of  lemon-juice  often  aids  in  effecting  a  cure.  In 
fevers,  lemonade  is  a  very  refreshing  and  useful  refrigerant  drink. 

ACETUM— VINEGAR. 

The  physical  properties  of  vinegar  are  too  well  known  to  need  de- 
scription here.  That  best  suited  for  medicinal  use  is  in  this  country  pre- 
pared from  cider,  and  should  have  a  trace  of  the  taste  of  cider.  Vinegar 


CARDIAC   DEPRESSANTS.  397 

may  be  substituted  for  lemon-juice  as  a  basis  of  an  acidulous  drink  in 
fever  when  the  lemon-juice  is  not  to  be  had  ;  but  as  an  antiscorbutic  it  is 
certainly  very  much  inferior  to  it,  and  has  not,  that  we  are  aware  of,  been 
tried  in  rheumatism. 

Acetic  Acid*  (AciDUM  ACETICUM,  U.  S.)  is  a  colorless  liquid,  having 
a  pungent  odor,  free  from  empyreuma,  and  an  intensely  acid,  corrosive 
taste.  It  contains  thirty-six  per  cent,  of  the  monohydrated  acetic  acid, 
and  has  a  specific  gravity  of  1.047.  Glacial  or  Absolute  Acetic  Acid 
(  ACIDUM  ACETICUM  GLACIALE,  U.  S. )  is  now  official.  It  is  a  colorless 
liquid,  crystallizing  at  59°  F. ,  remaining  solid  at  temperatures  below  60° 
F. ,  and  actively  escharotic, — in  a  measure,  no  doubt,  owing  to  its  prop- 
erties of  dissolving  gelatin  and  gelatinous  tissue  and  of  effecting  a  partial 
solution  of  albuminous  matters.  Dilute  Acetic  Acid  (  ACIDUM  ACETICUM 
DILUTUM)  is  officially  prepared  by  the  addition  of  five  parts  of  water 
to  one  'part  of  acetic  acid,  and  should  have  the  specific  gravity  of 
1.008. 

Dilute  acetic  acid  or  its  equivalent,  vinegar,  acts  upon  the  skin  as  a 
powerful  stimulant  and  astringent,  causing  contraction  of  the  vessels  and 
great  whiteness,  so  that  it  is  often  very  useful  as  a  topical  application  in 
various  forms  of  dermatitis,  especially  sunburn,  and  also  in  bruises  and 
sprains.  We  have  found  it,  diluted  with  from  one  to  four  parts  of  water, 
a  very  grateful  drink  in  hcematemesis,  and  very  effective  in  arresting  the 
flow  of  blood.  Diluted  with  "two  or  three  times  its  bulk  of  water,  it  is 
occasionally  employed  as  an  injection  against  seat-worms ;  but  the  infu- 
sion of  quassia  is  preferable. 

The  use  of  acetic  acid  as  a  caustic  will  be  spoken  of  under  the  head- 
ing of  Escharotics. 

TOXICOLOGY. — Acetic  acid  in  any  of  its  more  concentrated  forms  is 
a  corrosive  poison,  and  death  has  been  produced  by  it  in  at  least  one  case 
(Orfila1).  The  symptoms  resemble  those  caused  by  mineral  acids,  and 
the  treatment  is  exactly  similar, — neutralization  by  an  alkali  or  its  car- 
bonate, or  by  some  substance,  such  as  soap,  containing  an  alkali,  and  the 
meeting  of  indications  as  they  arise. 

Oxalic  Acid  (  ACIDUM  OXALICUM)  has  been  asserted J  to  be  a  valuable 
emmenagogue,  but  it  is  chiefly  known  to  the  profession  as  a  poison.  In 
1874  Rabuteau2  announced  that  in  oxalic  acid  poisoning  the  nerves  and 
muscles  are  not  affected,  and  that  therefore  the  acid  acts  upon  the  nerve- 
centres.  This  has  been  confirmed  by  the  elaborate  researches  of  R. 
Kobert  and  B.  Kiissner,3  who  find  that  it  paralyzes  the  respiratory, 
vaso-motor,  and  other  motor  spinal  centres.  It  is  also  a  cardiac  poison, 
arresting  the  heart  in  systole.*  The  acid  is  eliminated  by  the  kidneys. 
As  a  poison,  oxalic  acid  figures  in  two  forms  :  that  of  simple  oxalic  acid, 

*  ACETOXUM,  U.  S.  Acetone. — Pyroacetic  Spirit. — This  substance,  which  mixes  in 
all  proportions  with  water,  alcohol,  and  ether,  is  recognized  in  the  last  U.  S.  Pharmaco- 
poeia on  account  of  its  large  use  in  pharmacy  as  a  solvent  for  fats,  resins,  and  various 
active  principles.  It  is  not  used  in  practical  medicine. 


398  GENERAL   REMEDIES. 

and  that  of  the  acid  potassium  oxalate,  or  salt  of  sorrel,  or  essential  salt  of 
lemons,  as  it  is  variously  termed  in  common  parlance.  The  symptoms 
produced  are  a  hot  acrid  taste  experienced  during  the  swallowing,  a 
burning  in  the  gullet,  soon  extending  to  the  stomach,  intense  abdominal 
pain,  vomiting  of  highly  acid,  greenish,  blackish-brown  or  bloody  mucus 
(rarely  of  arterial  blood),  collapse,  livid  surface,  cold  skin,  entire  pros- 
tration of  strength,  small,  irregular  pulse,  stupor,  unconsciousness,  some- 
times convulsions,5  and  finally  death.  In  some  cases  the  gastric  symp- 
toms are  very  prominent  ;  in  others  they  are  nearly  wanting,  and  the 
chief  manifestations  are  collapse  and  such  nervous  symptoms  as  almost 
complete  general  paralysis,  numbness,  and  finally  stupor  ;  indeed,  the 
patient  may  suddenly  fall  unconscious  immediately  after  the  ingestion  of 
the  poison.6  In  pregnant  women  abortion  or  at  least  death  of  the  foetus 
usually  occurs.  According  to  Taylor,  the  smallest  quantity  which  is 
known  to  have  caused  death  is  one  drachm.  An  ounce  usually  proves 
fatal,  but  has  been  recovered  from.  After  death  the  coats  of  the  stomach 
are  found  softened  and  swollen,  and  sometimes  perforated.7  Rabu- 
teau  affirms  that  the  blood  is  everywhere  scarlet  ;  but  this  is  certainly 
not  always  the  case  (Taylor8).  In  1879  Kobert  and  Kiissner  discov- 
ered that  oxalic  acid  will  produce  in  the  lower  animals  not  only  oxaluria 
and  albuminuria  with  tube-casts,  but  also  glycosuria.*  In  1883  Sarga- 
neck  discovered  sugar  in  the  urine  in  human  poisoning,  and  the  recent 
investigations  of  Kobert  have  shown  that  in  rabbits  and  cats  even  non- 
poisonous  doses  of  the  acid  cause  the  appearance  of  a  fermentable  sugar 
in  the  urine.  It  would  seem,  therefore,  that  glycosuria  should  hold  an 
important  place  among  the  diagnostic  symptoms  of  the  poisoning.  Ac- 
cording to  Kobert  and  Kiissner,  a  pathognomonic  post-mortem  lesion  is 
the  incrustation  of  the  urinary  tubules  with  crystals  of  oxalates.  In 
poisoning  by  oxalic  acid,  the  immediate  administration  of  an  antidote  is 
of  the  utmost  importance.  As  the  potassium  and  sodium  oxalates  are 
poisonous,  neither  potash  nor  soda  is  available  ;  but,  fortunately,  lime  or 
chalk  is  a  perfect  antidote  to  oxalic  acid,  forming  the  excessively  insolu- 
ble calcium  oxalate.  As  time  is  a  matter  of  so  much  importance,  very 
often  it  is  best  simply  to  scrape  "whitewash"  off  a  wall,  a  ceiling,  a  fence, 
or  wherever  it  may  be  at  hand,  rub  it  up  hastily  with  water,  and  admin- 
ister it  freely.  The  after-treatment  is  that  of  toxic  gastro-enteritis. 

As  an  emmenagogue,  oxalic  acid  has  been  used  in  all  forms  of  amen- 
orrhcea  with  asserted  great  success.  It  is  said  also  to  be  an  active  aborti- 
facient,  but  as  such  is  certainly  extremely  dangerous.  The  dose  usually 
given  is  half  a  grain  three  or  four  times  a  day,  but  F.  W.  Talley  has 
reported  serious  poisoning  as  produced  by  this  amount. 

Oxalic  acid  is  a  powerful  germicide.  According  to  O.  Loew,9  the  one 
per  cent,  solution  of  the  neutral  potassium  oxalate  is  very  active  in  the 
destruction  of  infusoria,  whilst  Howard  A.  Kelly  10  asserts  that  potassium 

*  Kobert  has  made  the  very  important  observation,  that  the  extract  of  Syzygium 
jambolanum  will  control  the  glycosuria  produced  by  oxalic  acid. 


CARDIAC   DEPRESSANTS. 


399 


permanganate  and  oxalic  acid  afford  the  only  known  practical  method  of 
perfectly  disinfecting  the  hands  of  the  surgeon.* 


REFERENCES. 


CARDIAC   DEPRESSANTS. 

1.  WOOD P.  M.  T.,  iii. 

2.  La  Nazione,  Aug.  1872. 

3.  FOTHERGILL.    .     .  B.  M.  J.,  1873. 

ANTIMONY. 


1.  ACKERMANN  .  . 

2.  SENTZ 

3.  RADZIEJEVVSKI  . 

4.  NOBILING    .  .   . 

5.  SOLOWEITSCHYK 

6.  RICHARDSON  .  . 

7.  BRINTON  .... 

8.  Mosso 

9.  MAYERHOFER  . 

10.  HUSEMANN    .  . 

11.  SALKOWSKY   .  . 

12.  TAYLOR  .... 
13- 

14. 

15.  MASOIN    .... 


.  V.  A.  P.  A.,  xxv.  531. 

.  In.  Dis.,  Dorpat,  1853. 

.A.  A.  P.,  1871. 

.  S.  Jb.,  cxl.  24. 

.  A.  E.  P.  P.,  xii.  440. 

.  L.  L.,  1856,  i. 

.  L.  L.,  1853,  ii.  599.    ^ 

.  S.  Jb.,  clxix.  236. 

.  Notlmagel's    Arzneimittel- 
lehre,  Berlin,  1870,  219. 

.  Toxicologie,  853. 

.  V.  A.  P.  A.,  1865,  xxxiv.  78. 

.  Guy  H.  R.,  Oct.  1857. 
Taylor's  Medical  Jurispru- 
dence, 1873,  309. 
N.  V.  M.  R.,  xxiv.  401*. 

.  A.  I.  P.,  1902,  ii. 


VERATRUM   VIRIDE. 

1.  WOOD P.  M.  T.,  iv. 

2.  Amer.    Journ.    Pharmacy, 

1865. 

3.  M.S.  Rep.,  xl.  372. 

4.  BLAKE Amer.  Med.  Weekly,  1874, 

No.  20. 
5-  P.  M.  T.,  xiv.  863. 

ARNICA. 

1.  B.  M.  S.  J.,  Jan.  1875 ;  Ann. 

de  Dermal,  et  de  Syph., 
1886,  vii. 

2.  HARE B.  M.  S.  J.,  Jan.  12,  1888. 

3.  BALDING L.  L.,  Dec.  1870. 

4.  B.  G.  T.,  Ixxvi. 

5.  L.  L.,  Nov.  1864. 

6.  THORN Virginia    Med.    Monthly, 

Sept.  1883. 

ACONITE. 

1.  CASH  and  DUNSTAN  .  Tr.  R.  S.  London,  1898, 

cxc.  243. 

2.  HARLEY St.  Thomas  Hosp.  Rep.,  v. 

3.  BOEHM  and    WARTMAJJN  .  Arbeit.    Physiol. 

Wiirzburger  Hochschule, 

1873- 

4.  LIEGKOIS  and  HOTTOT  .  J.  de  P.,  1861,  520. 


RINGER  and  MURRELL  .  J.  P.,  i.,  No.  4. 
PLUGGE    ....     V.  A.  P.  A.,  Ixxxvii.  410. 
MACKENZIE   .   .   .  Pract.,  xx.  100. 
GUILLAUD  .  .   .   .  A.  de  P.,  1875. 

EWERS A.  E.  P.  P.,  1873,  i. 

LABORDE   and    DUQUESNEL   .  Des   Aconits, 

Paris,  1883. 

ACHSCHARUMOW  .  A.  A.  P.,  1866. 
MATTHEWS    .  .  .  J.  Ex.  M.,  ii.,  No.  5. 

LEWIN PragerVierteljahrs.,cxxxi. 

NUNNELEY.   .   .   .  Proc.  Roy.  Soc.,  London, 

1870. 
BRUNTON  and  CASH  .  St.  Barthol.  Hosp.  Rep., 

1886,  xxii. 

REICHERT  ....  P.  M.  T.,  1881,  105. 
STEVENSON    .   .   .  Guy  H.  R.,  3  s.,  xxvi.  308. 

BASSOT Thesis,  Lyons,  1889. 

Ln6TE  and  VIBERT  .  An.  d'H.,  April,  1892. 


HYDROCYANIC  ACID. 

1.  VIETZ Med.  Jahrb.  d.  k.  k.  Oes- 

terreiches  Staat.,  1814,  ii. 

2.  SCHUBARTH   .   .   .  Horn's     Arch.     f.     Med. 

Erfahrung,  1824. 

3.  SOBERNHEIM    .   .  Handb.  d.  Prakt.  Toxicol- 

ogie,  Berlin,  1838. 

4.  COZE Gazette    M6d.    de    Paris, 

1849. 

5.  BISCHOFF  ....  Ueber  Vergift.  nebst  Ver- 

such.  an  Thieren,  mit 
Blausaure,  etc.,  Wien, 
1844- 

6.  PREYER Die  Blausaure,  Bonn,  1870. 

7.  GAETHGENS  .   .   .  Hoppe-Seyler's   Med. 

Chem.  Untersuch.,  Ber- 
lin, 1866. 

8.  HOPPE-SEYLER    .  V.  A.  P.  A.,  xxxviii.  475. 

9.  LECORCHE  and  MEURIOT  .  A.  G.  M.,  6  s.,  xi. 

10.  LASCHKEWITSCH  .  A.  A.  P.,  1868,  652. 

11.  HILLER  and  WAGNER  .  L.  L.,  1877,  ii.  933. 

12.  HtJNEFELD    .   .   .  Der   Chemistnus   in  d. 

thierisch.  Organis., 
Leipzig,  1840. 

13.  LEWISSON  .   .   .   .  A.  A.  P.,  1870  352. 

14.  LAZARSKI   ....  Wien.   Med.  Jahrb.,   1881, 

441. 

15.  BOEHM  and  KNIE  .  A.  E.  P.  P.,  ii.  137. 

16.  WAHL De  Vi  et  Effectu  Hydro- 

cyanato,  etc.,  Bonn,  1865. 

17.  ROSSBACH  and  PAPITZKY  .  C.  M.  W.,  1877, 

640. 


*  The  exact  method  practised,  by  Kelly  is  as  follows  :  i.  Scrubbing  the  hands,  with 
especial  attention  to  the  nails, — not  more  than  one  millimetre  in  length, — for  ten  minutes 
in  water  frequently  changed,  at  about  40°  C.  (104°  F.).  2.  Immersion  of  the  hands  in  a 
solution  of  potassium  permanganate,  made  by  adding  an  excess  of  the  salt  to  boiling  dis- 
tilled water,  until  every  part  of  the  hands  and  lower  forearms  is  stained  a  deep  mahogany 
red  or  almost  black  color,  followed  by  transfer  to  a  saturated  solution  of  oxalic  acid  until 
completely  decolorized  and  of  a  healthy  pink  color.  This  decolorization  is  accompanied 
by  a  sense  of  warmth,  due  to  chemical  reaction,  and  a  sharp  stinging  wherever  there  is 
any  abrasion  of  the  epidermis.  3.  Washing  off  the  oxalic  acid  in  warm  sterilized  water. 


400 


GENERAL  REMEDIES. 


REFERENCES.—  Continued. 


18.  JONES    .   .   .  . 

19.  KOLLIKER  .   . 

20.  STANNIUS   .   . 

21.  FUNKE        . 


23- 

24.  FAGGE 

25.  KEEN 


26.  BUNGE  .... 

27.  HAYASHI    and 

28.  McKehvay  .   . 


.   .  N.  Y.  M.  R.,  ii.  459. 

.   .  V.  A.  P.  A.,  x.  272. 

.   .  A.  A.  P.,  1858,  95. 

.   .  Sb.  G.  W.,  Leipzig,  1859, 

xi.  28. 

B.  M.  J.,  1884,  i.  409. 
.  .  Guy  H.  R.,  1868,  259. 
.  .  Proc.  Acad.  Nat. 

Phila.,  1869. 
.  .  A.  E.  P.  P.,  xii.  71. 
MUTO  .  A.    E.    P.    P., 

xlviii. 
.   .  A.  J.  M.  S.  1905  cxxix,  684. 


Sci., 


1902, 


VEGETABLE    ACIDS, 
i.  GASKELL     .   .   .   .  J.  P.,  iii.  49. 


TARTARIC    ACID. 


i.  MUNCH 


.   .  Arch.  d.Vereins.  f.  getnein. 
Arbeit.,  1863,  370. 

2.  JONES M.  T.  G.,  1854,  ix.  408. 

3.  DEVERGIE  ....  An.  d'H.,  1851,  ii. 

4.  TAYLOR Medical        Jurisprudence, 

London,  1873,  230. 

5.  Med.  Press  and  Circular, 

Nov.  1880. 


CITRIC  ACID. 

1.  SCHULZ D.  M.  W.,  1883,  ix.  398. 

2.  JONES M.  T.  G.,  1854,  ix. 

3.  KIONKA A.  S.  Z.,  1903,  ix. 

4.  MAASS Th.  M.,  1903,  xvii. 

ACETIC    ACID. 

i.  ORFILA Toxicologie,  ii. 

OXALIC  ACID. 

1.  G.  H.  M.  C.,  xxiii.  128. 

2.  RABUTEAU  ....  Gazette  M6d.,  1874,92. 

3.  KOBERT  and  KUSSNER  .  V.  A.  P.  A.,  Ixxviii. 

109. 

4.  Les  Nouveaux    Rem&des, 

1886,  ii.  290. 

5.  Guy  H.  R.,  1838,  ii ;  Dub- 

lin H.  R.,  1818,  ii. 

6.  .  Guy  H.  R.,  1874. 

7.  Ed.  M.  J.,  July,  i86i,vii. 

8.  TAYLOR Med.  Jurisprud.,  i.  224. 

9.  LOEW Sitzb.     d.     Gesellsch.     f. 

Morphol.   und    Physiol., 
1892,  viii. 

10.  KELLY Amer.    Journ.    Obstetrics, 

1891,  xxiv. 


ORDER    III.— NUTRIANTS. 


FAMILY  I.— ASTRINGENTS. 

ASTRINGENTS  are  those  drugs  which  cause  contraction  of  living  tis- 
sues. That  they  do  not  act,  as  has  been  supposed,  either  by  coagulating 
albumin  or  by  calling  into  action  the  muscular  function  is  demonstrated 
by  the  transitoriness  of  their  effects,  and  by  the  fact  that  they  influence 
tissues  containing  no  muscular  fibre.  Every  living  soft  tissue  appears  to 
possess  a  normal  degree  of  condensation,  which  may  be  departed  from 
on  either  hand  :  when  this  happens,  in  the  one  case  the  part  is  said  to  be 
relaxed,  in  the  other  to  have  its  tonicity  increased,  or  to  be  astringed. 
The  action  of  astringents  is  always  a  local  one, — i.e. ,  produced  not 
through  the  intervention  of  the  nervous  system,  but  by  direct  contact 
with  the  part  affected.  A  pure  astringent  should  be  capable  of  doing 
nothing  beyond  inducing  contraction  ;  but  in  reality  there  is  scarcely  such 
a  drug.  Astringents  are,  when  applied  too  freely,  irritants. 

The  concordant  experimental  results  reached  by  M.  Rosenstein *  and 
by  R.  Heinz 2  show  that  medium  solutions  of  tannic  acid,  alum,  and  the 
salts  of  lead,  zinc,  iron,  copper,  and  mercury  contract  the  blood-vessels  by 
a  direct  action.  When,  however,  the  solutions  are  too  strong,  according 
to  Heinz,  this  contraction  is  followed  by  dilatation.  Both  experimenters 
state  that  the  silver  nitrate  is  the  most  powerful  in  its  influence,  pro- 
ducing an  almost  permanent  contraction.  According  to  Rosenstein,  acids 
cause  dilatation  of  the  capillaries. 

The  clinical  results  obtained  by  the  use  of  astringents  in  the  treatment 
of  inflammation  can  hardly  be  due  to  their  action  upon  the  blood-vessels, 
but  seem  to  find  more  appropriate  explanation  in  the  discovery  of  Heinz, 
that,  locally  applied,  they  decidedly  check  the  out-wandering  of  the  white 
blood-corpuscles,  probably,  as  he  thinks,  by  modifying  the  wall  of  the 
blood-vessel. 

The  chief  indication  for  the  use  of  an  astringent  is  the  existence  of 
relaxation.  Local  relaxation  is  commonly  due  to  previous  over-excite- 
ment. Thus,  a  throat  is  relaxed  after  over-use,  or  after  inflammation. 

Astringents  are  more  efficient  as  local  than  as  general  remedies,  but 
in  cases  of  inflammation  care  must  be  taken  to  use  them  in  such  a  way 
that  they  shall  not  act  as  irritants.  Applied  too  soon  or  too  vigorously, 
they  may  do  harm.  These  remarks  are  scarcely  applicable  to  some 
of  the  mineral  astringents,  such  as  lead  and  silver  nitrate,  which  really 

401 


402  GENERAL    REMEDIES. 

appear  to  have  sedative  properties,  and  may  with  care  be  used  advan- 
tageously in  all  stages  of  inflammation,  whenever  there  are  distention  and 
relaxation  of  the  blood-vessels,  although  the  general  action  of  the  part 
be  that  of  nutritive  excitement. 

Closely  allied  to  relaxation  is  over-secretion,  and  astringents  are  con- 
stantly used  to  check  morbid  discharges.  Indeed,  these  discharges  are 
often  simply  the  result  of  relaxation.  Thus,  A'sp  has  experimentally 
proved  that  division  of  the  intestinal  nerves  and  consequent  paralysis 
and  relaxation  of  the  vessels  are  followed  by  free  watery  secretion.  In 
such  cases  the  indication  for  astringents  is  very  plain.  But  when  a 
morbid  discharge  represents  a  high  degree  of  inflammation,  the  same 
care  must  be  practised  in  the  use  of  astringents  as  in  treating  other  local 
inflammations.  Especially  is  this  true  since  free  secretion  is  often  nature's 
method  of  relieving  local  inflammation.  Thus,  when  abnormal  alvine 
discharges  are  dependent  upon  intestinal  relaxation,  astringents  are  most 
valuable,  but  when  they  are  dependent  upon  enteritis  or  colitis,  astringents 
may  do  harm. 

If  the  morbid  discharge  by  its  profuseness  endangers  life,  as  in  serous 
diarrhoea,  astringents  are  urgently  demanded.  Very  rarely,  if  ever,  are 
these  discharges  other  than  paralytic  in  their  origin  ;  even,  however,  if 
they  be  due  to  over-action,  an  astringent  may  be  necessary  to  check  their 
excessiveness. 

Another  indication  for  the  use  of  astringents  is  to  check  hemorrhage, 
and  the  same  general  reasoning  is  applicable  to  this  as  to  the  other  indi- 
cations. Hemorrhage  dependent  upon  over-action  demands  other  treat- 
ment than  by  astringents.  Sometimes  in  these  cases  it  is  necessary, 
however,  to  check  the  hemorrhage  at  all  hazards,  and  then  astringents 
may  be  used  in  conjunction  with  other  measures,  although  they  may  be 
to  some  extent  contra-indicated.  Some  of  the  astringents  are  employed 
locally  to  check  hemorrhage  due  to  traumatic  or  other  ruptures  of  ves- 
sels. In  such  cases  the  astringents  are  employed  as  styptics,  and  do  not 
act  so  much  by  their  astringency  as  by  coagulating  the  albumin  of  the 
blood  and  thus  forming  a  clot  and  mechanically  arresting  the  flow. 

Under  certain  circumstances  there  seems  to  be  a  general  relaxation  or 
loss  of  tone  throughout  the  whole  system,  which  may  be  best  met  by  a 
consentaneous  use  of  tonics  and  astringents. 

VEGETABLE   ASTRINGENTS. 

The  active  principle  of  the  vegetable  astringents  is  tannic  acid,  and 
as  it  is  almost  their  sole  therapeutic  principle  and  represents  them  very 
closely,  it  seems  proper  first  to  consider  it,  and  afterwards  to  point  out 
any  especial  therapeutic  virtues  the  crude  drugs  of  the  class  may  possess. 

ACIDUM    TANNICUM— TANNIC   ACID.     U.S. 

There  are  two  generic  varieties  of  tannic  acid,  the  gallo-  and  the  kino- 
tannic  :  of  these  the  former  yields,  upon  exposure  to  the  air  in  a  moist 


ASTRINGENTS.  403 

state,  gallic  acid,  the  latter  a  gelatinous,  inert  substance.  They  are 
further  distinguished  by  the  color  of  the  precipitates  which  they  yield 
with  the  persalts  of  iron  ;  gallo-tannic  acid  producing  a  blue-black,  kino- 
tannic  a  green-black  color. 

The  official  tannic  acid — the  gallo-tannic  acid — is  obtained  by  treating 
powdered  galls  with  washed  ether,  which  on  standing  separates  into  two 
strata,  the  upper  of  which  is  ethereal  and  contains  chiefly  the  coloring- 
matter  and  other  impurities.  The  lower  watery  stratum  contains  the 
tannic  acid,  which  is  recovered  by  evaporation. 

Commercial  tannic  acid  is  a  light,  feathery,  non- crystalline  powder, 
of  a  yellowish-white  color,  a  faint  odor,  and  an  astringent,  somewhat 
bitter  taste.  When  absolutely  pure,  it  is  colorless  and  free  from  odor 
or  taste  other  than  that  of  astringency.  Its  reaction  is  strongly  acid, 
and  it  unites  freely  with  both  organic  and  inorganic  bases.  It  is  very 
freely  soluble  in  water,  even  more  so  in  glycerin,  somewhat  so  in  dilute 
alcohol,  scarcely  at  all  in  absolute  alcohol,  and  not  at  all  in  ether  free 
from  water.  With  salts  of  the  alkaloids  it  produces  a  whitish  precipitate 
(tannates),  very  soluble  in  acetic  acid  ;  with  persalts  of  iron,  a  black 
(bluish  or  greenish)  precipitate. 

PHYSIOLOGICAL  ACTION. — Applied  locally,  tannic  acid  is  a  very 
powerful  astringent,  causing  contraction,  and  in  the  case  of  a  mucous 
membrane,  great  dryness.  Sometimes,  when  it  is  used  very  freely,  its 
irritant  influence  seems  to  overcome  its  astringent  action,  and  we  have 
seen  diarrhoea  result  from  its  administration.  Several  experimenters 
(Rosenstein,1  Fikentscher 2)  have  denied  that  it  causes  contraction  of 
the  blood-vessels,  because  when  they  applied  it  to  the  exposed  mesentery 
of  a  "  Cohnheim  frog,"  stasis  of  the  blood,  with  dilatation  of  the  vessels, 
not  preceded  by  contraction,  occurred.  Daniels,3  however,  using  rabbits, 
obtained  different  results,  and  Lewin  has  shown  that  the  method  of  ex- 
perimentation was  faulty.  Clinical  experience  proves  that  tannic  acid 
applied  to  relaxed  mucous  membranes  affects  their  whole  substance. 

Absorption  and  Elimination. — Although  it  was  formerly  believed 
that  owing  to  the  activity  with  which  tannic  acid  coagulates  albumin  it 
was  incapable  of  absorption,  under  certain  circumstances  a  small  amount 
of  an  alkaline  tannate  may  be  absorbed  and  circulate  in  the  blood  ;  but 
although  a  small  portion  of  it  may  get  into  the  blood  as  a  tannate,  what 
is  absorbed  is  chiefly  various  decomposition  products.  Gallic  acid  has 
been  found  in  the  urine  after  the  administration  of  tannic  acid,  but 
according  to  Morner  the  amount  is  less  than  one  per  cent,  of  the  tannic 
acid  ingested.  When  given  in  large  amounts  it  mostly  escapes  absorp- 
tion, and  passes  out  with  the  faeces  unchanged. 

Thrown  rapidly  into  the  blood,  tannic  acid  causes  a  fatal  thrombosis  ;  but 
Lewin  *  asserts  that  when  it  is  injected  slowly  and  in  moderate  quantities  the  re- 
sulting albumin  tannate  is  held  in  solution  by  the  alkaline  carbonates.  He  has 
also  discovered  that  while  tannin,  in  five  per  cent,  solution,  precipitates  peptones 
out  of  watery  solution,  it  is  powerless  in  the  presence  of  hydrochloric  acid.  As- 


4o4  GENERAL  REMEDIES. 

suming  the  correctness  of  the  investigations  of  Lewin,  it  is  plain  that  tannic  acid, 
when  put  in  the  stomach  in  small  doses,  must  to  some  extent  be  absorbed  unchanged. 
Lewin  also  asserts  that  it  is,  at  least  in  part,  eliminated  unaltered,  as  he  has  fre- 
quently recovered  it  from  the  urine.  At  the  same  time  it  seems  very  probable  that 
most  of  the  tannic  acid  is  converted  into  gallic  acid,  either  in  the  stomach  before 
absorption  or  subsequently  in  the  system,  since  in  the  viscera  of  a  rabbit  poisoned 
with  it,  Schroff 5  found  only  gallic  acid  ;  and  according  to  Clarus,5  the  greater  part 
of  ingested  tannic  acid  can  be  recovered  from  the  stools  as  albumin  tannate  or  as 
gallic  acid.  The  recent  researches  of  Stockman6  afford  a  possible  reconciliation  of 
the  results  of  Lewin  with  those  of  the  the  older  observers.  Stockman  finds  that 
when  tannic  acid  is  given  to  the  lower  animals  only  a  trace  of  it  appears  in  the 
blood,  while  gallic  acid  can  be  obtained  in  abundance  from  the  urine,  with  occa- 
sionally a  small  amount  of  tannic  acid.  If,  however,  sodium  tannate  be  given, 
tannic  acid  appears  in  abundance  in  the  urine,  with  a  little  gallic  acid.  The  expla- 
nation offered  by  Stockman  of  this  is  probably  correct, — namely,  that  tannic  acid  is 
usually  converted  in  the  stomach  into  an  albuminous  tannate,  which  is  dissolved 
with  great  difficulty  in  the  intestinal  juices,  so  that  time  is  afforded  for  the  con- 
version of  the  tannic  into  gallic  acid,  whereas  an  alkaline  tannate  is  absorbed  at 
once  and  rapidly  eliminated  unchanged. 

Wohler  and  Frerichs  have  also  found  gallic  acid  with  pyrogallic  acid 
in  the  urine  after  the  exhibition  of  tannic  acid. 

After  its  conversion  and  absorption  tannic  acid  still  possesses  astrin- 
gent properties.  Lewin  has  shown  that  in  frogs  poisoned  with  it  the 
muscles  are  shortened  and  narrowed,  and  when  loaded  stretch  less  and 
recover  their  original  length  more  nearly  than  do  normal  muscles. 
Kuchenmeister 7  and  Hennig  state  that  in  poisoned  cats  the  spleen  is 
notably  diminished  in  size  and  increased  in  firmness  ;  and  Lewin  has 
found  in  rabbits  that  tannic  acid  causes  primary  arrest  of  the  urinary 
secretion,  followed  by  a  marked  increase  of  the  flow. 

THERAPEUTICS. — As  tannic  acid  undergoes  in  the  system  partial  con- 
version into  gallic  acid,  the  latter  is  to  be  preferred  to  it  when  the  part 
to  be  acted  on  can  be  reached  only  through  the  circulation.  As  a  local 
application,  tannic  acid  is  much  more  powerful  than  gallic  acid.  Lo- 
cally applied  it  may  be  used  to  overcome  relaxation,  as  in  spongy  gums, 
mercurial  sore  mouth,  hemorrhoids,  and  chronic  sore  throat.  To  check  hem- 
orrhage it  may  be  used  whenever  the  source  of  the  flow  can  be  reached 
directly,  as  in  epistaxis,  h&matemesis,  hemorrhage  from  the  bowels,  etc. 
To  arrest  excessive  secretion  it  may  be  employed  locally  in  leucorrhoea, 
diarrhea,  old  abscesses,  chronic  ulcers,  excessive  perspiration,  osmidrosis, 
and  various  diseases  of  the  skin.  It  is  also  often  very  useful  for  the  pur- 
pose of  hardening  parts  exposed  to  friction,  as  in  cases  of  sore  nipples 
and  tender  feet. 

TOXICOLOGY. — Tannic  acid  can  scarcely  be  called  poisonous  ;  although 
Rollet  reports  the  case  of  a  young  girl  in  whom  a  very  large  quantity  of 
it  induced  severe  gastric  and  abdominal  pains,  with  obstinate  vomiting 
and  constipation,  fever,  and  general  malaise.  Both  Schroff  and  Judell 
assert  that  eighty  grains  of  it  cause  no  symptoms  of  importance  in  the 
rabbit. 


ASTRINGENTS.  405 

As  an  antidote  it  is  useful  in  tartar  emetic  poisoning,  forming  an  in- 
soluble antimony  tannate.  It  is  also  the  best  chemical  antidote  for  the 
poisonous  alkaloids  ;  but,  as  the  compounds  it  makes  with  them  are 
slowly  dissolved  by  the  fluids  of  the  alimentary  canal,  it  must  always  be 
followed  by  emetics  and  cathartics. 

ADMINISTRATION. — When  given  to  act  on  the  stomach,  as  in  hsema- 
temesis,  tannic  acid  should  be  in  powder,  ten  to  twenty  grains  (0.6-1.2 
Gm. ).  When  the  bowel  is  to  be  influenced,  as  in  diarrhoea,  the  drug 
should  be  administered  in  pill,  three  to  five  grains  (0.2-0.3  Gm.),  so 
that,  if  possible,  it  may  pass  the  pylorus  undissolved.  For  local  use  the 
glycerite  of  tannic  acid  (GLYCERITUM  ACIDI  TANNICI,  U.  S. ,  twenty  per 
cent. )  may  be  employed,  or  the  ointment  (UNGUENTUM  ACIDI  TANNICI, 
U.  S.,  twenty  per  cent.),  or  the  troches  (TROCHISCI  ACIDI  TANNICI, 
U.  S.,  one  grain  each).  Tannic  acid  enters  into  styptic  collodion  (CoL- 
LODIUM  STYPTICUM,  U.  S. ,  twenty  per  cent.). 

TANNIC  ACID  COMPOUNDS. 

A  number  of  compounds  of  tannic  acid  have  come  into  vogue,  some  of 
them  of  great  practical  value. 

TANNALBIN.  Tannin  albuminate. — This  is  a  light-brown  powder,  insoluble  in 
water  or  the  gastric  juice,  but  decomposed  by  the  alkaline  juices  of  the  intestines 
with  the  liberation  of  its  constituents.  It  is  tasteless,  odorless,  and  non-irritant. 
It  is  a  very  valuable  remedy  in  the  treatment  of  intestinal  catarrh  and  relaxation 
requiring  the  use  of  an  astringent,  acting  immediately,  persistently,  and  effectively, 
and  affording  in  many  cases  an  excellent  combination  with  bismuth  subnitrate.  It 
has  been  recommended  also  in  renal  conditions  associated  with  an  excessive  dis- 
charge of  albumin.  Dose,  twenty  to  forty  grains,  in  powder  (1.2-2.5  Gm.). 

TANNACOL.  Gelatin  tannate. — A  tasteless,  odorless  powder,  probably  identical 
in  its  therapeutic  application  to  tannalbin,  although  Rosenheim 8  affirms  that  it  is 
superior  in  that  it  is  less  apt  to  be  affected  by  the  gastric  juice,  and  is  of  greater 
uniformity  of  constitution.  Dose,  fifteen  to  thirty  grains  (1-2  Gm. ). 

TANNOPINE.  Tannon. — A  combination  of  tannic  acid  and  urotropin,  which  is 
said  to  contain  eighty-seven  per  cent,  of  the  acid,  and,  passjng  unchanged  through 
the  stomach,  to  undergo  decomposition  by  the  alkaline  juice  of  the  alimentary  canal. 
It  has  been  strongly  recommended  by  Schreiber  9  and  other  clinicians  in  the  treat- 
ment of  all  forms  of  diarrhoeas  requiring  an  intestinal  astringent.  Dose,  ten  to 
fifteen  grains  (0.8-1  Gm.). 

TANNOFORM. — The  tannoforms  are  combinations  between  tannins  and  formal- 
dehyde. Commercial  tannoform  is  the  condensation  product  of  gallotannic  acid  and 
formaldehyde.  It  is  a  light,  pinkish-white  powder,  which  is  believed  to  be  decom- 
posed by  the  alkaline  juices  of  the  intestines  with  the  setting  free  of  tannic  acid  and 
formaldehyde,  and  to  act,  therefore,  as  an  astringent  and  germicide.  It  has  been 
very  highly  recommended  by  numerous  practitioners  in  tuberculous  and  other  diar- 
rhoeas requiring  an  astringent,  both  in  adults  and  in  children,  given  in  doses  of  one- 
half  to  one  grain  (0.03-0.06  Gm. ),  in  capsules,  three  times  a  day. 

There  is  also  much  testimony  as  to  the  value  of  tannoform  as  an  external 
remedy.  A  dusting-powder  composed  of  one  part  of  tannoform  to  two  of  talc,  well 
rubbed  into  the  skin  of  the  body  morning  and  evening,  is  stated  by  Strassburger 


4o6  GENERAL  REMEDIES. 

and  others  to  be  very  efficient  in  the  preventing  of  night-sweats.    An  application  of 
dilute  alcohol  should  be  made  to  the  skin  just  before  the  use  of  the  tannoform. 

According  to  K.  Ullmann,  confirmed  by  F.  Merz,  tannoform  is  extremely 
efficient  in  hyperidrosis  of  the  feet ;  a  foot-bath  should  be  used  just  at  bedtime  and 
a  powder,  composed  of  one  part  of  tannoform  and  two  parts  of  talc,  should  be  well 
rubbed  in  between  the  toes  and  over  the  feet,  daily  for  eight  days.  The  effect  is 
said  to  last  many  weeks.  Tannoform  has  also  been  used  as  a  local  remedy  in 
various  external  ulcerations,  also  eczemas,  and  other  affections  of  the  skin. 

ACIDUM   GALLICUM— GALLIC  ACID.     U.  S. 

Gallic  acid  is  a  white,  powdery  substance,  in  fine  acicular  prisms,  sol- 
uble in  one  hundred  parts  of  cold  water,  in  three  parts  of  boiling  water, 
and  freely  soluble  in  alcohol  and  in  ether.  Its  taste  is  acidulous  and 
astringent. 

According  to  the  usual  method,  gallic  acid  is  prepared  by  the  ex- 
posure of  moistened  powdered  nutgalls  in  a  warm  place  for  a  month.  A 
species  of  fermentation,  with  the  development  of  a  peculiar  fungus,  is 
said  to  occur,  during  which  oxygen  is  absorbed,  carbonic  acid  is  evolved, 
and  glucose  and  gallic  acid  are  produced.  M.  Sacc1  has,  however,  denied 
this,  affirming  that  the  change  is  simply  one  of  hydration,  tannic  acid 
being  an  anhydride  of  gallic  acid.  Tannic  acid  also  may  rapidly  be  con- 
verted into  gallic  acid  by  the  action  of  dilute  sulphuric  acid. 

Gallic  acid  produces  with  persalts  of  iron  a  bluish  precipitate,  with  lime- 
water  a  whitish  precipitate,  changing  to  blue  and  then  to  violet  or  pur- 
plish,— all  of  these  precipitates  being  gallates.  It  does  not  coagulate  gel- 
atin or  albumin,  and  is,  therefore,  not  a  styptic.  As  an  astringent  it  is 
less  powerful  than  tannic  acid.  It  escapes  from  the  body  through  the 
kidneys. 

THERAPEUTIC  ACTION. — Gallic  acid  is  not  nearly  so  efficient  as  tan- 
nic acid,  when  applied  locally,  but  should  always  be  preferred  when  the 
part  is  to  be  reached  through  the  medium  of  the  circulation.  It  is  useful 
as  an  astringent  in  hemoptysis,  hczmaturia,  colliquative  sweats,  etc.  It 
has  been  recommended  in  bronchorrhcea  and  in  the  profuse  expectoration 
of  chronic  phthisis.  In  our  hands,  however,  it  has  completely  failed  in 
the  latter  affections.  In  Bright1  s  disease,  when  there  is  an  abnormally 
large  secretion  of  highly  albuminous  urine,  it  may  lessen  very  materially 
the  excretion  of  albumin. 

ADMINISTRATION. — The  dose  of  gallic  acid  is  ten  to  thirty  grains 
(o.  6-2  Gm. )  in  capsules  or  powder,  repeated  pro  re  nata. 

GALLA— GALLS.     U.  S. 

Galls  are  vegetable  excrescences  which  are  produced  by  the  deposi- 
tion of  the  ova  of  insects.  They  occur  on  almost  all  kinds  of  plants, 
even  on  fungi,  but  the  official  gall  is  developed  on  the  Quercus  lusitanica 
by  the  act  of  the  fly  Cynips  gallae  tinctorise.  There  are  in  commerce  two 
varieties  of  galls,  derived  chiefly  from  the  Levant.  The  blue  or  green 
galls  are  globular,  solid  bodies,  from  the  size  of  a  pea  to  that  of  a  hick- 


ASTRINGENTS.  407 

ory-nut,  externally  smooth,  or  more  commonly  marked  with  large  tuber- 
cles. They  are  the  young  galls  which  have  been  gathered  before  the 
ova  of  the  fly  have  hatched,  or  before  the  caterpillar  has  eaten  out  the 
interior  of  its  birthplace.  The  white  galls  are  large,  light,  hollow  bodies, 
with  a  hole,  through  which  the  Cynips  has  escaped  after  having  fed  upon 
the  interior  during  its  whole  larval  life.  They  contain  but  little  tannic 
acid,  and  are  of  comparatively  little  value. 

THERAPEUTICS. — The  sole  value  of  galls  is  as  the  source  of  tannic 
acid.  As  galls,  they  should  not  be  used  in  medicine  ;  the  tincture 
(TINCTURA  GALL^E — twenty  per  cent.,  U.  S.)  and  the  ointment  (UN- 
GUENTUM  GALL^E — twenty  per  cent. ,  U.  S. )  are  still  sometimes  used  but 
are  inferior  to  preparations  of  tannic  acid. 

GAMBIR.     U.  S. 

Under  the  name  of  catechu  the  U.  S.  Pharmacopoeia  of  1 890  recognized 
the  extract  of  Acacia  catechu.  It  occurs  in  masses  of  various  shapes,  or 
in  small  fragments,  of  a  dull  reddish-brown  color,  and  having  a  bitterish, 
astringent,  and,  after  a  time,  sweetish  taste.  At  present  the  U.  S. 
Pharmacopoeia  concurs  with  the  British  in  recognizing  only  gambir  or  pale 
catechu.  The  extract  of  the  Uncaria  gambir  occurs  in  small  cubes,  about 
an  inch  in  diameter,  lighter  than  water,  pale  yellowish  within,  deep  yel- 
lowish or  reddish-brown  externally.  Both  gambir  and  true  catechu  con- 
tain kino-tannic  acid  and  are  powerful  astringents.  Dose,  for  diarrhoea, 
twenty  to  thirty  grains  (1.5-2  Gm. ).  Dose  of  the  compound  tincture 
(TINCTURA  GAMBIR  COMPOSITA — five  per  cent.,  U.  S. ),  one  to  three 
fluidrachms  (4-12  C.c.)  ;  the  troches  (TROCHISCI  GAMBIR,  U.  S. ), 
contain  one  grain  each. 

KINO— KINO.     U.  S. 

The  inspissated  juice  of  Pterocarpus  marsupium  and  of  other  trees. 
It  occurs  in  small,  irregular,  angular,  shining,  reddish,  brittle  fragments, 
of  a  bitterish,  highly  astringent,  and,  after  a  time,  sweetish  taste.  There 
are  four  varieties, — the  East  India,  West  India,  Botany  Bay,  and  African. 
Of  these,  the  first  is  common,  the  second  rare,  and  the  last  two  are  never 
seen  in  our  market.  Kino  contains  kino-tannic  acid,  and  its  therapeutic 
powers  are  identical  with  those  of  catechu.  Dose,  twenty  to  thirty  grains 
(1.5-2  Gm. )  ;  of  a  tincture  (TINCTURA  KINO — five  per  cent.,  U.S.), 
one  to  four  fluidrachms  (4-16  C.c.). 

H.3EMATOXYLON— H-dEMATOXYLON.  U.  S. 

The  heart- wood  of  Haematoxylon  campechianum,  or  logwood-tree, 
a  native  of  Central  America, — a  dense,  heavy  wood  of  a  deep  reddish- 
brown  color,  containing,  besides  kino-tannic  acid,  a  crystalline  principle, 
Hamatin  or  Hcematoxylin,  which  when  pure  is  yellow,  but  readily  yields 
red  or  purple  dyes.  According  to  F.  Combemale,*  haematoxylin  is  capa- 

*  Bull.  Gen.  de  Therap.,  1894,  cxxvii. 


408  GENERAL  REMEDIES. 

ble  of  causing  a  fatal  intoxication,  commencing  with  rigors  and  fever  and 
ending  in  vomiting,  anuria,  coma,  and  collapse. 

Haematoxylon  is  a  mild,  efficient  astringent,  valued  on  account  of  its 
sweetish  taste.  It  is  readily  taken  by  children,  but  is  sometimes  objected 
to  on  account  of  the  staining  of  the  diapers  by  the  blood-red  stools  which 
it  produces.  Dose  of  extract  (EXTRACTUM  H^EMATOXYLI,  U.  S. ),  ten 
to  thirty  grains  (0.65-2  Gm. ). 

The  following  formula  offers  an  efficient  and  elegant  remedy  for  diarrhceas  of 
relaxation  ;  the  proportions  may  be  varied  to  suit  individual  cases.  R  Ext.  haema- 
toxyli,  jii ;  Acid,  sulph.  aromat.,  f  giii ;  Tinct.  opii  camph.,  f  ^iss  ;  Syrupi  zingib- 
eris,  q.  s.  ad  f  %  vi.  M. — Dose,  a  tablespoonful,  properly  diluted. 

KRAMERIA— RHATANY.     U.  S. 

The  roots  of  Krameria  triandra,  of  Peru,  and  of  Krameria  ixina,  of  northern 
South  America.  Rhatany  contains  kino-tannic  acid  and  is  a  powerful  astringent, 
similar  in  virtue  to  kino  and  catechu,  but  is  never  administered  in  powder.  Dose 
of  the  extract  ( EXTRACTUM  KRAMERIA,  U.  S. ),  five  to  ten  grains  (0.3-0.6  Gm. )  ; 
of  the  tincture  (TINCTURA  KRAMERIA — twenty  per  cent.,  U.  S. ),  half  to  one  flui- 
drachm  (2-4  C.c. )  ;  of  the  fluid  extract  (FLUIDEXTRACTUM  KRAMERIA,  U.  S. ), 
twenty  minims  (1.25  C.c.). 

HAMAMELIS— HAMAMELIS.     U.  S. 

Under  the  names  of  Hamamelidis  cortex  and  Hamamelidis  folia,  the  U.  S. 
Pharmacopoeia  recognizes  respectively  the  bark  and  twigs,  and  the  leaves  of  the 
Hamamelis  virginica.  There  is  no  reason  for  believing  that  the  two  drugs  differ 
in  physiological  or  therapeutic  properties  except  that  the  cortex  is  probably  the 
stronger  of  the  two. 

Originally  in  the  form  of  a  proprietary  remedy,  subsequently  in  the  official  prep- 
aration, Hamamelis  has  been  enormously  used  in  the  United  States  as  a  local 
embrocation  for  bruises  and  sprains,  also  as  an  application  to  inflamed  mucous 
membranes.  It  has  been  carefully  studied  by  various  chemists,  but  no  active  prin- 
ciple has  been  found  in  it  except  tannic  acid  and  traces  of  a  volatile  oil.  According 
to  researches  of  W.  Straub1  its  tannic  acid  taken  into  the  stomach  is  converted  into 
gallic  acid,  and  as  such  eliminated  ;  although  when  injected  intravenously  it  in  part 
escapes  with  the  urine  unchanged.  Under  the  name  of  Hamamelin  two  substances 
are  sold  in  commerce,  one  greenish  and  the  other  brownish  ;  the  first  probably 
derived  from  the  leaves  of  the  plant,  the  second  from  the  bark,  each  containing 
tannic  acid.  That  the  volatile  oil  of  hamamelis  is  not  a  factor  in  any  therapeutic 
activity  of  the  drug  seems  to  be  shown  by  the  fact  that  a  very  concentrated  distil- 
late was  found  by  H.  C.  Wood  to  have  the  same  action  upon  frogs  as  the  same 
amount  of  distilled  water.  The  therapeutic  value  of  distilled  preparations  of  hama- 
melis would  appear,  therefore,  to  depend  upon  the  alcohol  which  they  usually  con- 
tain, the  rubbing  with  which  they  are  applied,  and  the  faith  with  which  they  are 
received  by  the  patient.  Fluidextractum  Hamamelidis  Foliorum,  U.  S.,  may  be 
used  in  doses  of  one-half  to  two  fluidrachms  (2-8  C.c..),  as  an  internal  astringent 
in  varicose  veins,  diarrhoea,  hemorrhoids,  etc.  Aqua  Hamamelidis,  U.  S.,  Water 
of  Hamamelis,  used  as  an  embrocation,  may  be  taken  internally  in  doses  of  two 
fluidrachms  (8  C.c.). 

QUERCUS  ALBA,  U.  S.,  and  QUERCUS  TINCTORJA  are  the  inner  barks  of  the 
trees  whose  names  they  bear, — the  white  and  the  black  oak  respectively.  The  latter 
is  a  rough,  yellowish-brown  bark,  which  is  used  in  dyeing,  under  the  name  of 


ASTRINGENTS.  409 

quercitron.  On  account  of  its  imparting  readily  its  color,  it  is  rarely,  if  ever, 
employed  in  medicine.  White  oak  bark  also  stains,  but  not  nearly  so  deeply  as 
does  black  oak  bark,  and,  containing  a  large  percentage  of  gallo-tannic  acid,  is 
used  as  a  means  of  making  cheap  astringent  infusions  for  baths,  vaginal  washes, 
etc.,  also  in  powder  for  poultices.  The  dose  of  the  fluid  extract  (FLUIDEXTRACTUM 
QUERCUS,  U.  S.  )  is  thirty  minims  (2  C.c.). 

ROSA  GALLICA,  U.  S.,  is  the  dried  petals  of  the  half-opened  flowers  of  the 
hundred-leaved  rose.  They  are  of  a  deep  red  color,  of  a  pleasant  astringent  taste, 
and  contain  a  small  percentage  of  gallotannic  acid,  red  coloring  matter,  and  a 
trace  of  volatile  oil.  Sulphuric  acid  changes  their  infusions  or  tinctures  to  a  bright 
red  color.  They  are  almost  destitute  of  therapeutic  virtues,  but  their  preparations, 
except  the  fluid  extract,  are  used  as  elegant  vehicles.  The  U.  S.  Pharmacopoeia 
recognizes  a  fluid  extract  (FLUIDEXTRACTUM  ROS^E  U.  S.  ),  a  honey  (MEL  ROS^E  — 
twelve  per  cent.),  a  confection  (CONFECTIO  ROS.E,  U.  S.),  and  a  syrup  (SYRUPUS 
—  fluid  extract,  12.5  per  cent). 


ROSA  CENTIFOLIA,  U.  S.,  or  Pale  Rose,  contains  little  tannic  acid,  with  a  vola- 
tile oil,  and  is  used  simply  on  account  of  its  pleasant  odor  :  out  of  it  are  prepared 
rose-water  (AQUA  ROS.S:,  U.  S.  )  and  the  very  elegant,  bland  emollient  ointment, 
cold  cream  (UNGUENTUM  AQU^E  ROS.E,  U.  S.  ). 

GERANIUM,  U.  S.,  is  the  rhizome  of  Geranium  maculatum  Linn.,  an  indigenous 
herbal  plant.  It  contains  a  large  percentage  of  gallotannic  acid,  and  has  been  used, 
especially  boiled  in  milk,  in  the  diarrhoea  of  children.  Dose,  twenty  to  thirty  grains 
(1.2-2  Gm.).  Dose  of  the  fluid  extract  (FLUIDEXTRACTUM  GERANII,  U.  S.  ), 
thirty  minims  to  a  fluidrachm  (2-4  C  c.). 

RHUS  GLABRA.  U.  S.  —  The  fruit  of  berries  of  the  sumach  contain  a  very  large 
percentage  of  tannic  and  malic  acids.  They  are  not  used  internally,  but  their 
fluid  extract  (FLUIDEXTRACTUM  RHOIS  GLABR^E,  U.  S.  )  affords  a  very  superior 
gargle  in  anginose  affections.  It  may  be  diluted  with  from  two  to  four  parts  of 
water,  and  potassium  chlorate  added  to  saturation. 

AGARIC.  —  Under  the  name  of  Agaric  various  species  of  fungi  belonging  to  the 
genus  Boletiis  have  been  employed  from  time  to  time  in  medicine.  Of  these  the 
white  agaric,  or  purging  agaric  of  writers,  is  obtained  from  Boletus  laricis,  the 
fungus  of  the  European  larch.  It  contains  a  whitish,  very  bitter  acid,  variously 
known  as  agaric  acid,  or  agaricinic  acid,  slightly  soluble  in  cold  water,  moderately 
so  in  hot  water.  According  to  the  researches  of  Hofmeister,1  agaric  acid  has  upon 
the  lower  animals  very  little  influence  except  in  arresting  the  secretion  of  sweat  by 
paralyzing  the  peripheral  nerves  of  the  sweat-glands.  Both  the  impure  extract, 
known  in  commerce  as  agaricin,  and  agaric  acid  have  been  extensively  used  for  the 
purpose  of  arresting  colliquative  sweats,  and  in  our  experience  have  proven  valuable 
remedies.  The  only  untoward  effect  ever  produced,  even  by  the  largest  dose,  is 
irritation  of  the  gastro-intestinal  canal.  Two  to  five  grains  (0.13-0.3  Gm.  )  of  the 
agaricin  may  be  given  three  times  a  day,  commencing  with  the  smaller  dose  and 
increasing.  According  to  Hofmeister,  the  dose  of  the  pure  acid  is  from  one- 
sixteenth  to  one-third  of  a  grain  (0.004-0.02  Gm.  ). 

COTARNINE  HVDROCHLORATE.  Stypticin.  —  This  salt,  which  is  obtained  by 
oxidizing  narcotine,  occurs  in  yellow  crystals,  readily  soluble  in  water  and  alcohol. 
Falk  *°  found  that  cotarnine  caused  in  frogs  paralysis  by  depression  of  the  motor 
side  of  the  spinal  cord,  and  in  warm-blooded  animals  acts  as  a  depressant  both 
upon  the  cerebral  cortex  and  motor-cord,  causing  narcosis  with  paralysis.  He 
further  determined  that  it  has  no  direct  influence  upon  the  circulation  ;  and  that 
upon  the  respiration  it  acts  as  a  primary  stimulant  and  secondary  depressant, 


4io  GENERAL  REMEDIES. 

causing  death  by  central  asphyxia  when  given  in  toxic  dose.  Abundant  clinical 
evidence  has  been  published  to  show  that  cotarnine  is  a  valuable  remedy,  as  first 
stated  by  Freund,  in  menorrhagia  as  well  as  in  pulmonic  and  other  internal 
hemorrhages.  It  is  said,  also,  to  be  a  powerful  local  haemostatic.  Cotarnine 
gauze,  or  absorbent  cotton  saturated  with  cotarnine,  has  been  greatly  praised  by 
dentists  and  surgeons. 

As  Mohr *  in  his  experiments  with  the  drug  failed  to  produce  uterine  contrac- 
tions it  seems  probable  that  cotarnine  arrests  hemorrhage  by  some  sort  of  astringent 
action,  or  by  directly  affecting  the  blood  ;  but  further  physiological  investigation  is 
imperative  for  decision.  In  excessive  menstruation  half  a  grain  may  be  given  three 
or  four  times  a  day  for  four  days  before  the  expected  discharge  ;  the  dose  being 
increased  to  one  grain  when  menstruation  appears.  In  haemoptysis  three  grains 
may  be  administered  at  once  subcutaneously,  and  repeated  in  half  an  hour  if 
required. 

MINERAL  ASTRINGENTS. 

ALUMEN— ALUM.     U.  S.     (POTASSIUM  ALUM.) 

Owing  to  the  cheapness  of  ammonia  the  double  salt  of  alumina  and 
ammonium  has  been  largely  substituted  for  the  true  alum,  which  contains 
potash  and  is  alone  recognized  by  the  U.  S.  Pharmacopoeia.  The  physi- 
cal qualities  of  the  two  salts  are  identical,  but  the  ammonia  alum,  when 
triturated  with  lime,  betrays  its  nature  by  the  evolved  gas.  Alum  occurs  in 
octahedral  colorless  crystals,  which  are  often  aggregated  into  large  masses. 
Its  taste  is  astringent,  acidulous,  and  sweetish.  It  is  soluble  in  nine  parts 
of  water  at  59°  F.  and  in  one-third  part  of  boiling  water.  It  is  slightly 
efflorescent,  and  when  heated  parts  with  its  water  of  crystallization  and  is 
converted  into  a  white  powder  (ALUMEN  EXSICCATUM,  U.  S. ,  or  Dried 
Alum}.  The  alkalies  and  their  carbonates,  lime,  magnesia,  and  its  car- 
bonate, potassium  tartrate,  and  lead  acetate  are  incompatible  with  alum. 

PHYSIOLOGICAL  ACTION. — According  to  the  statements  of  G.  B.  Wood 
and  A.  Stille,  alumina  can  be  detected  in  the  urine  of  persons  to  whom 
alum  has  been  given,  so  that  it  or  its  derivatives  must  find  a  way  into  the 
blood.  Locally,  it  is  when  in  dilute  solution  a  powerful  astringent  ;  when 
in  concentrated  form,  irritant ;  as  dried  alum,  mildly  corrosive.  Given  in 
large  dose  to  the  lower  animals  it  produces  violent  gastro-intestinal  irrita- 
tion, and  is  capable  in  man  of  causing  death,  preceded  by  violent  vomiting, 
bloody  purging,  and  haematuria.  (Case,  Kramolik1. )  One  ounce  and 
five  drachms  of  burnt  alum  caused  death  in  eight  hours.* 

THERAPEUTICS. — Internally  alum  is  of  no  value  in  practical  medicine, 
except  it  be  in  colica  pictonum,  in  which  it  is  asserted  by  authority  that 
it  is  a  valuable  remedy  even  though  there  be  no  lead  in  the  primes  -vice  to 
be  precipitated  by  it  as  a  sulphate.  As  a  local  drug  it  is  of  especial  value 
as  a  styptic  by  virtue  of  its  powerful  coagulative  influence  on  albumin; 
and  we  have  known  it  usefully  given  by  atomization  in  hemoptysis.  It  is 
sometimes  used  in  various  anginas  and  other  inflamed  conditions  of  the 
mucous  membrane,  but  is  so  irritant  and  attacks  so  strongly  the  teeth  as 
to  greatly  lessen  its  value. 

In  colliquative  sweats,  sponging  at  bedtime  with  alum-water,  or,  still 
better,  the  taking  of  an  alum-water  bath,  will  often  materially  aid  in  re- 


ASTRINGENTS.  411 

storing  the  lost  tone  to  the  skin.  In  chronic  ulcers  with  exuberant  spongy 
granulations,  and  in  certain  conditions  of  conjunctivitis,  alum  curd  is  often 
applied  with  benefit.  When  it  is  desired  to  exert  an  astringent  action  upon 
the  internal  organs,  alum  is  not  nearly  so  useful  as  other  members  of  the 
class.  As  a  mechanical  emetic  it  is  too  uncertain  to  be  of  much  value. 
Astringent  dose,  ten  to  twenty  grains  (0.6  Gm. ) ;  emetic  dose,  a  teaspoon- 
ful  of  the  powder  for  a  child,  a  tablespoonful  for  an  adult.  Alum  curd  may 
be  made  by  dissolving  two  drachms  in  a  pint  of  milk,  and  straining,  or  by 
rubbing  the  alum  with  white  of  egg.  Dried  alum  is  sometimes  used  as  a 
very  mild  escharotic  for  the  destruction  of  exuberant  granulations  in  ulcers. 

ALUMINII  SULPHAS.  U.  S.  Aluminum  sulphate.—  This  substance  usually 
occurs  in  flattened  crystalline  cakes,  of  a  sour-sweetish,  somewhat  astringent  taste 
and  acid  reaction.  It  is  soluble  in  twice  its  weight  in  water.  It  is  an  irritant  active 
astringent,  with  some  germicidal  power.  Its  solution,  in  strength  varying  from 
half  an  ounce  to  the  pint  up  to  saturation,  has  been  used  as  a  local  application  for 
foul  ulcers^  leucorrhcea,  and  other  allied  diseases.  In  solid  form,  or  even  in  satu- 
rated solution,  it  is  very  feebly  caustic. 

ALUMINII  HYDROXIDUM.  U.  S.  Aluminum  hydroxide. — Aluminum  hydrate 
is  a  white,  amorphous,  odorless,  tasteless,  permanent  powder,  insoluble  in  water 
and  alcohol,  which  has  been  used  as  a  feebly  astringent,  desiccant  powder  in  inflam- 
matory conditions  of  the  skin. 

PLUMBUM— LEAD. 

When  a  soluble  salt  of  lead  is  applied  to  a  part  in  not  too  concen- 
trated solution,  it  acts  as  an  astringent  and  sedative.  Owing  to  the  con- 
traction of  the  vessels  which  is  induced,  the  tissue  becomes  blanched, 
and  any  inflammatory  action  which  may  be  present  is  remarkably  affected. 
When  in  concentrated  solution,  the  mildest  preparations  of  lead  are  capa- 
ble of  acting  as  irritants,  increasing  or  even  originating  inflammation. 
When  the  salts  of  lead  are  taken  internally  in  therapeutic  doses,  no 
decided  symptoms  are  generally  induced,  except  a  diminution  of  the  se- 
cretions, especially  of  those  of  the  alimentary  canal.  Sometimes,  when 
full  therapeutic  doses  are  exhibited,  a  slight  lowering  of  the  frequency 
and  force  of  the  pulse  *  is  said  to  result,  but  we  have  never  witnessed 
this.  The  insoluble  are  much  less  irritant  than  the  soluble  lead  prepa- 
rations. 

TOXICOLOGY. — Acute  lead-poisoning  is  usually  produced  by  a  soluble 
salt,  notably  the  acetate  ;  f  but  a  case  reported  by  Freyer l  shows  that 
white  lead  and  other  insoluble  preparations  may  act  as  violent  and  even 
fatal  irritant  poisons.  When  the  acetate  is  ingested  in  toxic  dose,  the 
first  symptom  is  usually  a  persistent,  sweet,  somewhat  metallic  taste  ; 
this  in  a  few  minutes  is  followed  by  vomiting,  which  may  or  may  not  be 
preceded  by  nausea.  The  matters  vomited  are  often  milky  white,  from 

*  See  Laidlaw's  Observations  (quoted  byStill€),  Therapeutics,  second  edition,  i.  177. 
t  According  to  Husemann  (Handbuch  der  Toxicologie},  the  poudre  de  succession, 
so  famous  during  the  reign  of  Louis  XIV.,  was  composed  chiefly  of  lead  acetate. 


412  GENERAL    REMEDIES. 

the  presence  of  lead  chloride.  A  severe  burning  persistent  pain  in  the 
abdomen  now  comes  on,  and  is  accompanied  by  a  craving  for  drink. 
There  may  be  obstinate  constipation,  or  diarrhoea  may  ensue  :  in  either 
case  the  stools  are  generally  black  from  the  sulphuret  of  lead.  In  certain 
cases  a  state  of  collapse  is  developed  ;  the  pulse  falls  to  40  or  50  per 
minute,  the  voice  is  lost,  the  face  is  deadly  pale,  the  lips  are  livid,  and 
syncope  seems  imminent.  In  other  instances  the  nervous  symptoms  may 
predominate,  or  they  may  accompany  those  of  disordered  circulation  : 
cramps  in  the  calves  of  the  legs,  severe  neuralgic  pains  in  the  extremi- 
ties, paralysis  and  anaesthesia,  vertigo,  stupor,  may  any  or  all  of  them 
be  present.  In  fatal  cases,  coma,  with  or  without  convulsions,  finally 
develops.  A  distinctive  mark  of  lead-poisoning,  which  occasionally  is 
present  very  early,  is  the  blue  line  upon  the  gums.  After  death  inflam- 
mation of  the  alimentary  mucous  membrane  is  sometimes,  but  not  always, 
found.  One  ounce  of  lead  acetate,  subacetate,  or  nitrate  may  take  life. 

The  treatment  of  acute  lead-poisoning  consists  in  the  evacuation  of 
the  stomach,  the  exhibition  of  sodium  or  magnesium  sulphate,  and  the 
meeting  of  the  indications  as  they  arise.  The  Epsom  and  Glauber's 
salts  act  as  chemical  antidotes,  by  precipitating  the  insoluble  sulphate  of 
lead,  and  also,  if  in  excess,  empty  the  bowel  of  the  compound  formed. 
To  allay  the  gastro-intestinal  irritation,  albuminous  drinks  should  be  given 
and  opium  freely  exhibited. 

Subacute  and  chronic  lead-poisoning  are  almost  always  accidental,  and 
occur  most  frequently  among  those  whose  occupation  exposes  them  to 
daily  contact  with  some  compound  of  the  metal  ;  manufacturers  of  white 
lead,  painters,  glaziers,  and  similar  artisans  furnish  the  greater  number 
of  victims.  They  may  be  seen,  however,  in  persons  of  all  conditions  of 
life,  for  although  neither  food  nor  drink  is  often  purposely  adulterated 
with  lead,  yet  it  is  frequently  introduced  into  the  system  accidentally 
along  with  those  necessities.  Lead  pipes  are  habitually  used  for  the  con- 
veyance of  water,  and  when  the  water  contains  salts  of  lime,  even  in 
minute  proportion,  no  evil  results,  because  through  the  decomposition 
which  ensues  insoluble  coatings  are  deposited  on  the  inside  of  the  pipes.* 
When  the  water  is  pure,  no  such  reactions  occurring,  the  lead  is  slowly 
dissolved  in  the  form  of  a  carbonate,  and  poisoning  may  result.  Poi- 
soning has  also  frequently  resulted  from  the  employment  of  cosmetics 
and  hair-dyes,  from  the  internal  or  external  medical  use  of  lead  prepa- 
rations,2 from  cooking  bread  with  painted  wood,*  from  imperfectly  burnt 
pottery,4  from  habitually  biting  silk  thread  which  rascally  manufacturers 
often  load  with  lead  to  give  weight  to  it,f  from  lead  bullets  retained 


*  For  an  elaborate  article  on  the  chemical  relation  of  water  to  lead,  see  Schmidt's 
Jahrbiicher,  cxliv.  279. 

t  Chronic  lead-poisoning  is  produced  much  more  frequently  by  insoluble  than  by  sol- 
uble compounds  of  lead,  but  it  is  probable  that  any  saturnine  preparation  may  cause 
it.  Thus,  lead  chromate  has  killed  numbers  of  people.  (See  Med.  News,  ii.  1887;  also 
Therap.  Gaz.,  iv.). 


ASTRINGENTS.  413 

in  the  body  (Vucetio5),  and  from  diachylon  used  as  an  abortifacient 
(Ransom64),  etc. 

That  form  of  lead-poisoning  in  which  colic  is  the  most  decided  symp- 
tom is  often  spoken  of  as  subacute.  After  some  days  of  malaise  and 
wretchedness,  or  sometimes  very  suddenly,  the  victim  is  taken  with 
abdominal  colicky  pains,  which  increase  in  intensity  until  they  become 
very  severe.  They  are  constant,  with  occasional  exacerbations,  are  some- 
times dull,  sometimes  sharp,  are  generally  described  as  twisting,  and 
seem  to  centre  around  the  umbilicus.  Very  often  there  are  repeated 
retching  and  vomiting.  The  walls  of  the  abdomen  are  retracted,  rigid, 
knotted  ;  the  bowels  are  obstinately  costive  ;  the  tongue  is  contracted 
and  whitish,  the  appetite  gone,  and  the  thirst  sometimes  excessive. 
Neuralgic  pains  in  the  thorax  and  in  the  extremities  are  of  frequent 
occurrence.  In  some  cases  the  conjunctiva  is  distinctly  icteroid.  This 
condition,  which  is  known  as  colica  pictonum,  or  lead  colic,  may  after  a 
time  abate,  and  the  patient  convalesce  ;  more  usually,  however,  the 
attacks  recur  from  time  to  time,  becoming  gradually  less  severe  and  dis- 
tinctive, and  the  patient  gradually  passes  into  chronic  lead-poisoning. 
Occasionally  the  colic  increases  in  severity  ;  sometimes  the  course  of  the 
disease  is  interrupted  by  various  violent  accidents. 

The  cases  of  chronic  lead-poisoning  vary  so  much  in  their  symp- 
tomatology as  almost  to  baffle  concise  description.  It  has  seemed  to  us 
that  the  symptoms  can  best  be  studied  by  arranging  the  cases  in  groups, 
but  it  must  be  remembered  that  in  nature  not  only  do  these  groups  shade 
into  one  another,  but  also  that  there  are  all  kinds  of  mixed  cases, — cases 
which  offer  simultaneously  or  successively  symptoms  of  two  or  more  of 
these  various  groups. 

The  first  group  contains  the  great  bulk  of  cases  of  chronic  lead-poi- 
soning, at  least  as  seen  in  this  country.  The  symptoms  consist  of  failure 
of  health,  more  or  less  digestive  disturbance,  and  double  wrist-drop, — 
i.e. ,  paralysis  of  the  extensor  muscles  of  each  hand.  Not  rarely,  the 
only  noticeable  symptom  is  the  wrist-drop,  the  general  health  seeming  to 
be  very  good.  The  true  nature  of  such  cases  can  usually  be  at  once 
recognized  by  the  bilateral  character  of  the  wrist-drop,  cerebral  and 
pressure  paralyses  being  almost  invariably  unilateral.  We  have  seen, 
however,  bilateral  pressure  palsy,  and  also  one  or  two  cases  of  unilateral 
plumbic  wrist-drop,  due  to  a  local  absorption  of  lead,  in  artisans  who  had 
one  hand  much  of  the  time  in  a  preparation  of  the  metal.  Similar  cases 
have  been  recorded  by  Manouvriez.6*  The  wrist-drop  may  exist  alone, 
but  not  rarely  there  is  with  it  anaesthesia  of  the  affected  part,  or  some- 
times of  the  shoulders  or  other  unparalyzed  portion  of  the  body.  When 
the  paralysis  is  complete,  the  electro-contractility  of  the  muscles  is  in 
great  part  or  altogether  absent. 

The  rarer  forms  of  chronic  lead-poisoning  may  be  divided  into  the 
cerebral,  the  periphero-spinal,  and  the  nutritive. 

»  See  also  La  France  Med.,  1882,  i.  829. 


4i4  GENERAL    REMEDIES. 

In  the  cerebral  cases  should  be  included  those  which  are  commonly 
spoken  of  as  encephalopathia  saturnina,  or  saturnine  cerebritis* 

In  cerebral  cases  of  lead-poisoning  the  violent  brain  symptoms  may  develop 
with  great  suddenness,  or  may  be  preceded  by  some  days  of  headache,  giddiness, 
sleeplessness,  disturbed  vision,  strabismus,  tinnitus  aurium,  psychical  aberration,  or 
other  prodromes  of  brain  disturbance.  Delirium,  which  is  among  the  chief  mani- 
festations of  the  fully  formed  condition,  may  be  mild,  but  is  often  maniacal  ;  stupor 
may  replace  or  alternate  with  it ;  and  violent  epileptiform  convulsions,  ending  in 
coma,  are  not  infrequent.  These  convulsions  are  usually  the  precursors  of  death, 
but  recovery  may  occur  even  after  the  most  severe  symptoms.8 

Without  the  development  of  such  severe  symptoms,  headache,  loss  of  memory, 
giddiness,  somnolence,  hemianaesthesia,  disturbance  of  the  special  senses,  aphasia, 
monoplegia,  hemiplegia,  or  multiple  cerebral  palsies  may  occur  during  chronic 
lead-poisoning.  Death,  preceded  by  severe  cerebral  symptoms,  may  take  place 
without  organic  lesion  ;  but  usually,  when  focal  symptoms  have  been  present,  local- 
ized alteration  of  brain  structure,  secondary  to  diseases  of  the  cerebral  vessels,  or 
to  chronic  inflammation  of  the  brain  or  its  membranes,  can  be  detected.  Some- 
times the  cerebral  symptoms  are  uraemic ;  indeed,  true  plumbic  encephalopathy 
and  plumbic  uraemia  from  contracted  kidney  may  coexist.  Again,  the  more  serious 
affection  may  be  masked  by  a  saturnine  hysteria,  since  cases  have  been  reported  by 
Charcot  and  by  Dutil  in  which  hysterical  hemianaesthesia,  amaurosis,  anosmia,  loss 
of  sense  of  taste,  and  other  cerebral  symptoms  have  been  the  outcome  of  a  major 
hysteria  due  to  chronic  lead-poisoning.  Such  cases  as  these  probably  occur  only 
in  individuals  of  previously  hysterical  temperament,  and  must  be  extremely  rare  in 
persons  not  of  the  so-called  Latin  race. 

Disturbances  of  vision  are  so  frequent  and  so  marked  in  lead-poisoning  as  to 
deserve  special  mention.  They  have  been  classified  by  de  Schweinitz  as  follows  : 

1.  Transient  amblyopia,  without  ophthalmoscopic  change. 

2.  Amblyopia  without  fundus  lesions,  or  with  congestion  of  the  nerve-head,  and 
with  central  scotomas  analogous  to  those  caused  by  other  toxic  agents. 

3.  Optic  neuritis,  or  neuro-retinitis,  either  specifically  due  to  lead  or  secondary 
to  changes  in  the  brain  or  kidneys. 

4.  Optic  nerve  atrophy,  either  consecutive  to  a  plumbic  papillitis  or  retrobulbar 
neuritis,  or  due  to  a  primary  effect  of  the  lead  on  the  visual  organ. 

5.  Various  types  of  retinitis,  vasculitis,  and  perivasculitis,  either  primarily  due 
to  lead  or  secondary  to  nephritis. 

Strabismus  from  muscular  paralysis  is  sometimes  of  saturnine  origin.! 

The  second  group  of  cases  of  chronic  lead-poisoning  consists  of  those 
in  which  the  nerve-symptoms  apparently  originate  below  the  cerebrum. 

In  the  present  group  belong  cases  such  as  have  been  reported  by  Putnam,  by 
Tisier,  by  Raymond,  and  by  G.  L.  Walton,  in  which  the  phenomena  resemble  those 
of  locomotor  ataxia,  except  in  the  presence  of  tenderness  over  the  nerve-trunks, 
preservation  of  the  tendon  reflexes,  or  some  other  atypical  symptoms.  We  have 
seen  several  cases  in  which  the  symptoms  resembled  those  of  an  acute  polio- 
myelitis, consisting  chiefly  of  wide-spread  paralyses  with  rapid  wasting  of  the 

*  George  F.  Crooke 7  reports  a  case  in  which  lead  plaster  taken  for  the  production  of 
abortion  caused  not  only  miscarriage,  but  also  fatal  brain  lesions,  preceded  by  choked 
disks,  albuminuria,  and  convulsions. 

t  For  discussion  of  details,  see  Beau  (Arch.  Gen.,  1848),  Manouvriez  (Arch,  de 
Physiol.  Norm,  et  Palholog.,  1870,  411 ;  1876,  762),  A.  De  Cours  (De  V Hemianczsthesia 
saturnine,  Paris,  1875),  Proust  (Progres  Mid.,  1879,  vii.  546),  Debove  (Ibid.,  99,  117), 
and  Alex.  VVestphal  (Archiv  fur  Psychiat.,  1887-88,  xix.). 


ASTRINGENTS.  415 

muscles.  These  cases  usually  can  be  differentiated  by  the  presence  of  violent 
neuralgic  pains,  paralysis  of  the  bladder  and  rectum,  or  other  atypical  symptoms. 
Similar  to  these  cases  are  those  spoken  of  by  G.  Lyon,9  in  which  a  rapid  general 
paralysis  spread  from  part  to  part,  until  at  last  aphonia  and  dyspnoea,  and  even 
death  from  asphyxia,  resulted.  Severe  intractable  chorea  has  been  produced  by 
lead.  Oscar  Buber 10  calls  attention  to  the  form  of  irregular  lead  palsy  in  which 
the  paralyzed  muscles  are  affected  with  peculiar  slow,  worm-like,  and  occasion- 
ally painful  contractions.  Disturbances  of  sensation  may  occur  in  lead-poisoning  ; 
anaesthesias  are,  perhaps,  not  very  rare,  and  violent  neuralgic  pains,  probably 
due  to  neuritis,  may  be  the  chief  manifestation.  In  a  case  of  H.  C.  Wood's  in 
which  the  diagnosis  was  confirmed  by  finding  lead  in  the  drinking-water  and  in 
the  urine  of  the  patient,  the  symptoms  were  intense  general  pruritus,  with  violent 
neuralgic  pains  shooting  through  the  rectum  and  the  urethra,  coming  on  at  night 
and  producing  an  insomnia  which  appeared  to  be  unconquerable.  The  lesion  is 
often  peripheral,  and  the  very  rapid  pulse  seen  in  some  cases  may  be  due  to  disease 
of  the  vagi,  which  Prevost  and  Binet u  have  found  degenerated. 

The  third  group  of  cases  comprises  those  in  which  the  poison  chiefly 
expends  itself  upon  glandular  or  visceral  organs,  or  in  producing  wide- 
spread nutritive  changes. 

It  would  seem  that  almost  any  of  the  vital  structures  may  undergo  degenera- 
tion. Potain 12  reports  a  case  of  saturnine  cirrhosis  of  the  liver ;  while  Valence 1S 
and  Claisse  and  Dupre"  u  call  attention  to  plumbic  parotiditis,  which  may  take  the 
form  of  a  slowly  progressive  chronic  hypertrophy  of  the  gland,  with  dryness  of  the 
mouth,  or  of  a  distinct  sclerosis,  or  there  may  be  .ulceration  of  the  orifice  of  Steno's 
duct  and  obstruction.  Rudolf  Maier 15  has  found  in  poisoned  animals  atrophic  de- 
generations of  the  intestinal  glands  and  walls.  Sailor K  found  in  twelve  cases  of 
saturnism  a  constant  reduction  in  the  secretion  of  hydrochloric  acid. 

Of  great  frequency  and  importance  are  the  lesions  produced  by  lead  in  the 
kidneys.  It  must  be  remembered  that  temporary  albuminuria  may  occur  in  lead- 
poisoning  without  serious  implication  of  the  kidneys ;  while,  on  the  other  hand, 
fatal  nephritis  may  exist  when  there  js  no  albumin  in  the  urine  ( LanceYeaux 1B ) .  A 
persistent  low  specific  gravity  of  the  urine  in  lead-poisoning  is  a  symptom  of  the 
utmost  gravity.  Geppert "  confirms  the  observation,  previously  made  by  Olivier, 
that  in  temporary  plumbic  albuminuria  many  isolated  kidney  epithelial  cells  may 
often  be  found  in  the  urinary  sediments  ;  and  it  is  evident  that  a  persistence  of  this 
condition  must  end  in  chronic  renal  disease.  After  death,  which  may  be  induced 
by  uraemia,  the  kidneys  are  found  contracted,  granular,  with  excessive  development 
of  the  fibrous  tissue  (followed  by  contraction)  and  great  thickening  of  the  walls  of 
the  blood-vessels  :  these  changes  are  identical  with  those  of  contracted  kidney  pro- 
duced by  gouty  and  other  irritant  poisons.  As  Ellenberger  and  Hofmeister  have 
shown  that  the  lead  is  chiefly  eliminated  by  the  kidneys,  the  frequency  of  plumbic 
nephritis  is  easily  explained  ;  but  it  is  not  readily  perceived  why  it  is  so  frequently 
associated  with  an  arthralgia  whose  course  and  lesions  closely  simulate  those  of 
chronic  gout.  Garrod  (1859),  Dickinson,  LanceYeaux,  Rosenstein,  Leyden,18  and 
other  authors  have  reported  so  many  cases  of  this  association  of  renal  and  gouty 
manifestations  that  it  can  scarcely  be  doubted  that  the  plumbism  is  the  cause  of  the 
gouty  symptoms,  and  not  simply  a  complication  of  gout.* 

There  are  certain  cases  of  lead-poisoning  which  do  not  conform  to  any 
of  the  types  as  yet  given. 

*  Consult  Deutsch.  Med.  Wochenschrift,  1883,  185,  351 ;  1884,  129 ;  also  Paul  Musehold 
(Die  Bleivergiflung,  Berlin,  1883).  We  have  ourselves  seen  one  case. 


416  GENERAL  REMEDIES. 

Among  these  very  irregular  cases  may  be  mentioned  those  reported  by  E. 
Levy,19  in  which  acute  asthma  was  produced  by  the  inhalation  of  the  dust  of  white 
lead.  Again,  chronic  saturnine  asthma  is  sometimes  seen  in  feeble,  narrow-chested 
people.  James  J.  Putnam20  calls  attention  to  the  fact  that  in  lead-poisoning  of 
children  the  legs  and  feet  are  commonly  paralyzed.  Pagliano 21  has  reported  a  case 
of  saturnine  facial  palsy.  It  has  been  abundantly  proved  both  by  clinical  experience 
and  by  experiments  made  upon  the  lower  animals  that  in  chronic  lead-poisoning 
the  metal  may  pass  through  the  placenta  into  the  fcetus,  causing  its  death,  with  sub- 
sequent abortion.* 

As  any  of  the  obscure  manifestations  of  lead-poisoning  may  exist,  and 
even  prove  fatal,  without  a  distinct  history  of  other  more  characteristic 
phenomena,  great  care  is  sometimes  necessary  to  avoid  being  misled,  and 
not  rarely  the  true  nature  of  saturnine  epilepsy  or  of  saturnine  albuminuria 
is  overlooked.  Hence  the  importance  of  the  blue  line  upon  the  gums 
•where  they  join  the  teeth,  which  is  very  common  in  persons  suffering  from 
lead-poisoning.  It  is  said  to  be  the  result  of  a  formation  of  lead  sul- 
phide in  the  walls  of  the  capillaries.  As  was  first  pointed  out  by  J.  J. 
Putnam,22  chronic  lead-poisoning  may  exist  without  this  blue  line  upon  the 
gums.  Under  such  circumstances,  if  the  symptoms  be  obscure  the  diag- 
nosis can  be  established  only  through  a  chemical  examination  of  the 
urine.f  The  practitioner  should  see  that  the  urine  which  is  to  be  sent 
to  the  chemist  for  examination  be  slightly  acidified,  that  directly  after 
passing  it  be  put  in  flint-glass  bottles,  and  that  it  be  at  least  a  quart  in 
quantity.  From  a  diagnostic  point  of  view  an  extremely  important  ob- 
servation, if  it  be  confirmed,  is  that  of  Deroide  and  Lecompt,23  who  assert 
that  there  is  in  the  urine  of  saturnine  patients  uroh&matoporphyrine,  a 
red  pigment,  soluble  in  ether,  water,  and  alcohol,  which  can  readily  be 
recognized  by  the  spectroscope. 

In  those  cases  of  lead-poisoning  which  pursue  a  slow  course  to  death 
the  paralysis  involves  after  a  time  the  extensors  of  the  lower  as  well  as 
of  the  upper  extremities,  epileptic  paroxysms  occur  at  intervals,  racking 
pains  shoot  through  the  limbs,  points  of  cutaneous  anaesthesia  appear, 
and  often  albuminuria  aids  in  producing  the  fatal  issue.  Gradually  the 
patient  becomes  more  and  more  cachectic,  general  cedema  and  the 
whitened  skin  betray  the  increasing  anaemia,  the  paralysis  extends  from 
muscle  to  muscle,  locomotion  becomes  impossible,  and,  if  a  convulsion  or 
other  accident  do  not  close  the  scene,  death  at  last  takes  place  from  loss 
of  power  in  the  respiratory  muscles. 

Plumbic  anaemia  is  probably  due,  at  least  in  part,  to  a  direct  action  of  the  lead 
upon  the  blood  or  the  blood-making  organs.  According  to  Malassez,"  the  red 
blood-corpuscles  during  the  anaemias  are  not  only  diminished  in  number,  but  also 
increased  in  size.  Sabrazes  and  Bourret62  have  found  in  the  blood  of  a  case  of 
serious  acute  lead-poisoning  normoblasts,  basophilic,  granular,  and  polychromatic 

*  See  Constantine  Paul  (Archiv  Gtn.,  1860,  xv.),  Legrand  and  Winter  (Compt.-Rend. 
Soc.  Biolog.,  1889),  and  B.  Annino  (Schmidt's  Jahrb.,  ccxliv.,  No.  n). 

t  For  an  elaborate  discussion,  see  leading  article  in  Therap.  Gaz.,  Dec.  1887;  Ibid., 
iii.  813,  and  iv.  92. 


ASTRINGENTS.  4*7 

cells ,  also  neutrophilic,  polymorphonuclear  leucocytes.  In  chronic  lead-poison- 
ing, Moritz  6J  found  granulation  of  the  basophilic  erythocytes,  and  was  able  to  pro- 
duce such  a  change  in  lower  animals. 

After  death  lead  has  frequently  been  detected  in  almost  all  of  the 
tissues. 

Heubel 25  found  most  of  it  in  the  bones,  and  less  in  the  muscular  than  in  the 
nervous  system.  Chatin26  obtained  from  the  cervical  spinal  cord  three  in  one  hun- 
dred and  fifty  parts.  In  the  studies  of  Ellenberger  and  V.  Hofmeister '"  the  liver 
and  kidneys  were  found  to  contain  the  most,  lead,  after  them  the  bones,  then  the 
nerve-centres,  and  finally  the  flesh.  Prevost  and  Binet  found  the  lead  in  all  the 
tissues,  but  believe  that  it  especially  accumulates  in  the  kidneys.*  G.  N.  Pitt28  re- 
ports finding  over  forty-seven  grains  of  the  lead  sulphite  in  nine  inches  of  the  colon. 

The  electro-muscular  contractility  is  affected  very  early  in  lead-poi- 
soning, and  may  be  lost  before  the  voluntary  movements.  It  is  stated 
by  M.  Raymond  that  the  short  extensor  of  the  thumb  preserves  its  func- 
tion when  all  the  other  extensor  muscles  are  paralyzed.  The  paralyzed 
muscles  are  finally  exceedingly  wasted,  and  their  structure  may  be  so 
totally  destroyed  that  scarcely  a  single  striated  fibre  can  be  found.  The 
nerve-trunks  are  lessened  in  size,  in  many  of  their  tubules  the  medulla 
has  been  replaced  by  fatty  granules,  and  in  some  cases  every  trace  of  the 
tubules  has  disappeared  and  the  nerve  has  been  reduced  to  a  fibrous 
cord. 


*A  question  of  the  most  serious  importance,  which  at  present  we  are  not  able  to  answer 
positively,  is  as  to  whether  sclerosis,  neuritis,  and  other  chronic  affections  of  the  nervous 
system  which  have  been  reckoned  as  idiopathic  or  of  unknown  origin  are  not  frequently 
the  outcome  of  an  entirely  latent  lead-poisoning.  In  a  remarkable  paper,  J.  J.  Putnam, 
of  Boston  (  Trans.  Assoc.  American  Physicians,  ii.),  describes  cases  entirely  apart  from 
recognized  types  of  lead-poisoning,  in  which  the  metal  was  found  in  the  urine.  These 
cases  may  be  grouped  as  follows  :  i.  Trembling  of  hands ;  sense  of  coldness  and  numb- 
ness in  toes  ;  lancinating  pains  in  legs ;  fatigue  on  exertion.  2.  Marked  progressive  spastic 
paraplegia,  with  myosis  and  pupillary  reactions ;  ataxia  and  some  atrophy  of  hands. 
3.  Progressive  weakness  and  stiffness  in  legs,  with  diffused  and  almost  universal  pains  ; 
marked  tremor.  4.  Temporary  pain  in  chest,  with  slight  dyspnoea ;  progressive  numb- 
ness, heaviness,  and  weakness  in  legs.  5.  Numbness  in  feet  and  legs,  with  impairment 
of  strength  ;  tremor  of  hands  and  tongue ;  some  wasting  of  small  muscles  of  hands ;  tem- 
porary retention  of  urine.  Closely  connected  with  this  subject  is  the  question  whether 
lead  may  not  be  for  a  length  of  time  in  the  system  and  appear  in  the  urine  without 
doing  injury  to  the  health.  In  a  paper  (Boston  Med.  and.  Surg.  Journ.,  1890,  cxxiii.) 
Putnam  brings  forward  more  facts,  whose  import  is  at  present  very  doubtful.  In  an 
examination  of  the  urine  of  sixty-eight  persons,  presenting  no  evidences  of  any  dis- 
arrangement of  health,  lead  was  found  in  the  proportion  of  about  seventeen  per  cent., 
while  the  urine  of  thirty-six  persons  suffering  from  chronic  and  subchronic  affection  of 
the  nerves,  nerve-centres,  and  spinal  cord  contained  lead  in  the  proportion  of  fifty  per 
cent.  In  the  last  group  were  cases  of  tremors  with  debility,  of  chronic  multiple  neuritis, 
multiple  sclerosis,  spastic  paraplegia,  muscular  atrophy,  epilepsy,  sciatica,  digestive  dis- 
orders, etc.  (Bost.  Med.  and  Surg.  Journ.,  1889,  cxxi.).  One  cannot  help  suspecting 
that,  owing  to  defective  water-supply,  Bostonians  are  especially  prone  to  contain  lead. 
For  a  minute  description  of  various  forms  of  lead  palsy,  see  Le  Salurnisme,  Meillere, 
Paris,  1903. 

27 


4i8  GENERAL   REMEDIES. 

According  to  the  researches  of  DegeYine,29  the  first  appearance  of  change  in  a 
nerve-trunk  consists  in  the  myeline  becoming  broken  up  into  blocks,  and  the  nature 
of  the  change  is  a  commingling  of  a  parenchymatous  and  an  interstitial  neuritis, 
which  both  De"ge"rine  and  Vulpian  have  traced  upward  as  far  as  the  anterior  spinal 
roots.  Lance'reaux,30Westphal,sl  Friedlander,32  and  others  may  be  cited  as  having 
found  very  distinct  peripheral  lesions  in  lead-poisoning.  Whether  these  lesions 
begin  in  the  nerve  or  in  the  muscles  cannot  be  considered  as  determined.  Bird- 
sail ss  reported  a  case  of  what  he  believed  to  be  a  plumbic  myositis,  and  Gourbault34 
describes  primary  alteration  in  the  nerves,  similar  to  those  seen  after  section,  as 
occurring  in  poisoned  guinea-pigs,  while  Debove  and  Reaut35  describe  the  first 
changes  as  resembling  those  of  subacute  myositis,  and  Friedlander  emphatically 
asserts  that  lessening  in  the  size  of  the  muscular  fibres  and  multiplication  of  the 
muscular  nuclei  precede  the  nerve-degeneration.  On  the  other  hand,  Vulpian,36 
Monakow,37  Oeller,38  and  a  number  of  other  observers*  have  noticed  structural 
changes  (poliomyelitis,  capillary  hemorrhages,  etc.)  in  the  spinal  cord  of  men  dead 
of  plumbism  ;  while  Popow  M  found  that  when  guinea-pigs  were  rapidly  poisoned  (six 
to  eight  days)  with  lead  there  was  produced  a  central  myelitis,  which  first  affected 
the  large  cells  of  the  gray  matter,  and  afterwards  involved  the  white  matter,  the 
peripheral  nerve-filaments  remaining  normal.  There  is,  however,  no  real  contra- 
diction, as  Popow  believes,  between  his  observations  and  those  of  Gourbault,40 
for  the  latter  poisoned  his  animals  very  slowly  (six  months),  and  it  is  not  im- 
probable that  the  rapidity  of  the  poisoning  had  an  influence  upon  the  seat  of  the 
lesion.  As  already  stated,  the  symptoms  of  plumbism  may  exactly  simulate  those 
of  general  poliomyelitis,  and  both  De'ge'rine  and  Leopold  Stieglitz 41  found  degen- 
eration of  the  motor  cells.  Karl  Schaffer42  believes  that  two  sharply  separated 
forms  of  degeneration  of  the  nerve-centres  occur  in  chronic  lead-poisoning, — one 
consisting  of  a  minutely  granular  destruction  of  the  protoplasm,  the  other  of  the 
homogenization  of  the  contents  of  the  cell. 

The  evidence  at  present  indicates  that  lead  is  capable  of  producing  a 
peripheral  neuritis,  and  also  a  centric  poliomyelitis,  which  may  or  may 
not  coexist  in  an  individual  case  ;  the  probabilities  being  in  favor  of  a 
peculiar  peripheral  neuritis,  as  the  primary  lesion  of  ordinary  plumbic 
wrist-drop  (see  paper  by  Schultze,4*  also  Prevost  and  Binet).  Hemor- 
rhages into  the  nerve-centres  sometimes  occur."  There  seems  to  be  no 
doubt  that  lead  really  affects  the  nutrition  of  almost  all  of  the  higher  tis- 
sues. In  saturnine  encephalopathy  changes  have  been  found  in  the  gan- 
glionic  cells  as  well  as  in  the  neuroglia,  with  stenosis  of  capillaries  and 
general  shrinkage  of  the  cortex  (see  O' Carroll45).  Marked  alterations 
are  not  rare  in  the  kidneys  and  other  glandular  organs,  and  general 
fibrosis  of  the  blood-vessels  is  probably  more  or  less  developed  in  every 
slowly  fatal  case  of  chronic  poisoning  (case,  Fisher46). 

The  excretion  of  lead  with  the  gall  is  very  active,  but  it  is  probable 
that  it  chiefly  escapes  from  the  body  with  the  urine.  The  elimination 
seems  to  be  capricious,  and  much  affected  by  potassium  iodide  and  by 
other  influences.* 

The  treatment  of  chronic  lead-poisoning  evidently  arranges  itself 
under  three  indications  :  first,  to  prevent  the  ingestion  of  more  of  the 
poison  ;  second,  to  aid  in  the  elimination  of  that  in  the  system  ;  third, 

*  For  references,  see  Arch.  f.  Psychiat.  und  Nervenkr. ,  xvi.  447. 
f  See  Melsens,47  Pouchet,48  Annuschat,49  and  Pouchet.50 


ASTRINGENTS.  419 

to  relieve  symptoms  and  restore  lost  functions.  In  lead  colic  the  last 
two  indications  are  met  by  purgatives,  to  which  opium  should  be  added 
to  relieve  pain.  It  is  often  necessary  to  use  the  most  powerful  drastics, 
such  as  croton  oil ;  but  senna,  salts,  and  other  of  the  milder  cathartics 
should  always  be  tried  first.  Alum,  it  is  asserted,  acts  in  some  unknown 
way  as  a  specific  in  lead  colic,  and  from  twenty  to  sixty  grains  of  it  may 
be  given  four  or  five  times  a  day  ;  but  our  experience  is  not  favorable 
to  its  use.  In  the  more  chronic  forms  of  lead-poisoning,  to  fulfil  the 
second  indication  baths  of  potassium  sulphuret  should  be  employed, 
and  potassium  iodide  be  administered  internally.*  As  the  result  of 
special  investigation,  Oddo  and  Silbert 51  conclude  that  the  elimination  of 
lead  through  the  skin  in  chronic  lead-poisoning  is  important,  that  it  is 
facilitated  by  injections  of  pilocarpine,  and  that  the  sulphur  baths  are 
valuable  in  the  treatment  of  chronic  lead-poisoning.  The  bath  should  be 
given  (A.  Eulenburg52)  in  a  wooden  tub,  two  or  three  times  a  week,  and 
should  contain  six  or  seven  ounces  of  the  salt.  The  patient,  during  the 
half-hour  of  his  continuance  in  it,  from  time  to  time  should  be  well  rubbed 
with  a  coarse  towel.  On  coming  out  he  is  to  be  thoroughly  washed  with 
warm  soapsuds.  The  dose  of  the  iodide  should  be  from  fifteen  to  twenty 
grains,  administered  after  meals,  in  dilute  solution.  A  case  is  reported  M 
in  which  galvanic  baths  were  used  successfully,  the  patient  being  placed 
in  the  bath  and  the  positive  pole  of  a  twenty-eight-cell  battery  applied  to 
the  nape  of  the  neck,  the  negative  to  the  feet.  When  severe  cerebral 
symptoms  arise,  treatment  is  of  little  avail,  and  should  be  largely  ex- 
pectant, f  In  cases  of  lead-poisoning  in  which  the  symptoms  resemble 
those  of  acute  poliomyelitis  we  have  used  ascending  doses  of  strychnine 
with  most  extraordinary  results,  rapidly  deepening  paralysis  being  almost 
at  once  controlled.  It  is  essential  that  the  strychnine  be  pushed  to  the 
point  of  systemic  intolerance.  It  is  best  to  administer  it  by  the  mouth, 
or  if  used  hypodermically  it  should  be  given  at  least  twice  a  day.  It 
may  possibly  prove  of  value  in  other  acute  forms  of  lead  palsy. 

*  As  the  result  of  a  careful  series  of  analyses,  J.  D.  Mann  (Brit.  Med.  Journ.,  1893, 
}.)  concludes  that  in  chronic  lead-poisoning  there  is  a  great  fluctuation  in  the  elimina- 
tion of  lead,  that  potassium  iodide  has  no  real  effect  in  increasing  the  elimination,  that 
lead  is  eliminated  from  the  intestines  even  more  freely  than  from  the  urine,  and  that  the 
previous  contrary  results  obtained  by  investigators  have  been  due  to  chance  coincidences 
of  the  iodide  treatment  with  increase  of  the  lead  excretions  from  other  cause.  He  recom- 
mends especially  general  massage,  and  confirms  to  some  extent  the  assertion  of  Tedes- 
chi,  that  this  massage  increases  remarkably  lead  elimination. 

t  It  seems  doubtful  whether  the  sulphur  baths  really  aid  elimination,  but  we  have 
seen  good  follow  their  use.  It  has  been  denied  that  the  iodide  acts ;  but  cases  are 
reported  in  which  lead  was  not  in  the  urine  before,  and  was  after  the  administration  of 
the  drug  (see  Brit.  Med.  Journ.,  1880,  ii.  1034).  Moreover,  John  Marshall  (  Therap.  Gaz., 
iv.  97)  has  shown  by  actual  experiment  that  potassium  iodide  in  solution  has  an  action  on 
the  insoluble  lead  carbonate  and  phosphate,  with  the  formation  of  a  soluble  lead  com- 
pound,— double  lead  and  potassium  iodide ;  and  therefore,  if  lead  taken  into  the  sys- 
tem be  deposited  in  the  tissues  as  insoluble  carbonate  or  phosphate,  these  latter  com- 
pounds, on  the  administration  of  potassium  iodide,  will  be  decomposed,  with  the  produc- 
tion of  a  soluble  lead  compound,  and  consequently  a  more  rapid  elimination  of  the  lead 
will  occur. 


420  GENERAL  REMEDIES. 

The  local  use  of  electricity  is  exceedingly  important  to  restore  the 
lost  function  of  nerve  and  muscle.  When  the  faradic  current  elicits  a 
response,  it  should  always  be  employed  ;  but  in  some  cases M  the  con- 
tinued current  retains  its  power  after  the  induced  has  lost  all  its  influence. 
The  rule  is  always  to  apply  that  current  which  causes  contraction  ;  if  both 
fail,  the  continued  current  should  be  used,  the  poles  being  reversed  at 
intervals  of  four  or  five  seconds.  The  electrical  stances  should  be  tri- 
weekly, each  lasting  about  fifteen  minutes,  and  they  should  be  persevered 
in  for  months.  We  have  seen  great  improvement  in  a  case  which  for  the 
first  four  months  yielded  no  results  ;  indeed,  long  after  voluntary  move- 
ment had  in  great  measure  returned,  no  form  of  electricity  would  cause 
contraction  of  the  affected  muscles.* 

PHYSIOLOGICAL  ACTION. — The  symptoms  of  acute  lead-poisoning 
are  chiefly  due  to  its  local  irritant  action,  but  those  of  chronic  poisoning 
are  of  wider  significance.  How  the  lead  is  absorbed  to  produce  them  is 
uncertain, — probably  as  an  albuminate.  All  the  compounds  of  lead  and 
albumin  as  yet  discovered  by  the  chemist  are,  however,  precipitated  by 
alkaline  carbonates,  and  cannot,  therefore,  exist  in  the  blood. 

The  symptoms  of  chronic  lead-poisoning  are  probably  in  great  part 
secondary  to  the  structural  alteration  produced  by  the  drug,  lead  being  a 
poison  to  all  forms  of  protoplasm.  Why  in  one  case  one  set  of  organs 
should  be  attacked  and  in  another  case  a  different  portion  of  the  body 
is  a  mystery.  The  nephritis  which  is  so  common  a  result  is  no  doubt 
connected  with  the  effort  to  eliminate  the  poison  from  the  system. 

The  chief  research  we  know  upon  the  effects  of  lead  upon  the  lower  animals  is 
that  of  Ernest  Harnack,55  who  employed  the  compound  of  lead  and  ethyl  first 
discovered  by  Loewig.  When  this  is  injected  into  animals  in  large  quantities  it 
causes  a  rapidly  fatal  train  of  symptoms  evidently  due  to  the  action  of  the  compound 
itself.  When,  however,  the  introduction  into  the  system  has  been  slow,  a  chronic 
poisoning  is  produced  by  the  lead  set  free  in  the  blood  and  tissues. 

Under  these  circumstances  a  constant  symptom  in  both  dogs  and  rabbits  is 
diarrhoea,  due  to  a  violently  increased  peristalsis,  with,  in  the  dog,  occasional 
attacks  of  colic.  Harnack  found  that  in  dogs  the  lead  ethyl  produces  violent  ex- 
citement, with  chorea,  convulsions,  etc.,  evidently  due  to  an  exciting  or  irritant 
action  upon  the  cerebrum,  and  believes  that  this  explains  the  saturnine  cerebral 
cases  sometimes  seen  in  man. 

The  chief  symptom  of  the  poisoning  in  frogs  was  a  progressive  palsy  of  mus- 
cular origin.  The  muscle  became  exhausted  on  repeated  galvanization  much  more 
rapidly  than  is  normal,  and  after  death  was  incapable  of  undergoing  complete  post- 
mortem rigidity.  The  peripheral  nerves  appeared  to  have  escaped  entirely.  The 
heart-muscle  snared  the  fate  of  the  voluntary  muscles.  The  muscular  action  of  the 

*  M.  Semmola  (Bull.  Acad.  de  Meet.,  1892,  xxviii.)  asserts  that  chronic  plumbism  can 
readily  be  cured  by  the  elimination  of  the  metal  from  the  urine  under  the  influence  of  a 
constant  galvanic  current.  He  applies  the  positive  pole  upon  the  tongue  and  the  negative 
pole  over  the  region  of  the  kidneys  for  a  while  ;  later,  places  the  positive  pole  upon  the 
sides  of  the  vertebral  column  and  the  negative  pole  upon  the  abdomen,  keeping  up  the 
application  for  five  to  twenty  minutes  each  day,  using  a  current  from  one  hundred  to  one 
hundred  and  fifty  milliamperes.  He  affirms  that  in  cases  in  which  no  lead  could  be  found 
in  the  urine,  after  three  or  four  days  of  treatment  the  lead  could  readily  be  detected  and 
that  its  quantity  gradually  increased. 


ASTRINGENTS.  421 

poison  was  excessively  pronounced  in  rabbits,  but  was  feeble  in  dogs  and  cats. 
Different  results  have,  however,  been  arrived  at  by  H.  von  Wyss,56  who  found  that 
the  loss  of  reflex  activity,  etc.,  in  the  frog  was  not  prevented  by  tying  an  artery  so 
as  to  protect  the  leg  from  the  poison,  and  that  the  protected  muscle  lost  its  power 
of  responding  to  electrical  stimulation  just  as  fast  as  did  the  one  reached  by  the 
lead.  He  concludes,  therefore,  that  the  paralysis  is  of  centric  origin.  Curci57  is 
stated  to  have  proved  that  lead  exerts  an  irritant  influence  upon  the  peripheral 
branches  and  ganglionic  centres  of  the  pneumogastric.  According  to  the  researches 
of  Ellenberger  and  Hofmeister,  in  the  sheep  toxic  doses  of  lead  greatly  depress  the 
elimination  of  urea. 

,  The  pulse  in  lead  colic  is  usually  very  hard  and  tense.  Sphygmo- 
graphic  studies  made  of  it  by  August  Frank  M  and  Ernest  Bardenhewer  w 
have  been  thought  to  indicate  a  condition  of  general  arterial  spasm,  and 
have  given  rise  to  the  theory  that  the  colic  is  caused  by  intestinal  anaemia 
from  vaso-motor  contraction.  Harnack,  however,  found  that  in  dogs  and 
rabbits  the  lead  ethyl  has  no  action  upon  the  vaso-motor  system  and 
does  not  produce  spasm  of  the  vessels.  Moreover,  he  determined  that 
both  the  diarrhoea  and  excessive  peristalsis  produced  in  dogs  were  arrested 
by  atropine,  which  ought  to  promote  rather  than  lessen  vaso-motor  con- 
traction. Lead  colic  in  man  is  probably  due  to  a  spasmodic  contraction 
of  the  intestines  so  powerful  as  to  arrest  peristalsis,  and  to  so  press  upon 
the  blood-vessels  as  to  force  the  blood  from  the  abdomen  into  the  general 
circulation.* 

The  following  preparations  of  lead  are  official  in  the  United  States 
Pharmacopoeia  : 

PLUMBI    OXIDUM— LEAD    OXIDE.     U.  S. 

Litharge,  which  is  prepared  by  blowing  air  through  melted  lead, 
occurs  in  small  yellowish  or  orange-colored  scales,  which  are  insoluble  in 
water  and  alcohol,  but  are  soluble  in  acetic  or  dilute  nitric  acid  and  in 
a  warm  solution  of  the  fixed  alkalies.  It  is  occasionally  used  as  a 
desiccant  astringent  powder  for  ulcers,  but  its  chief  employment  in  medi- 
cine is  in  the  making  of  EMPLASTRUM  PLUMBI,  or  Lead  Plaster,  U.  S. , 
which  consists  chiefly  of  lead  oleomargarate.  Lead  plaster  occurs  in 
grayish,  cylindrical  rolls,  which  become  adhesive  at  the  temperature  of 
the  body,  and,  spread  upon  kid,  is  sometimes  used  as  a  protective  to 
parts  exposed  to  pressure,  or  to  superficial  ulcers  or  abrasions.  EMPLAS- 
TRUM RESIN^E,  or  Resin  Plaster,  U.  S. ,  or  adhesive  or  sticking  plaster, 
is  made  by  incorporating  resin  with  lead  plaster,  and,  spread  upon  linen, 
is  much  used  in  surgery  for  mechanical  purposes.  EMPLASTRUM 
SAPONIS,  or  Soap  Plaster,  U.  S. ,  is  made  by  the  addition  of  soap  to  lead 
plaster.  It  is  employed  chiefly  as  a  protective. 

PLUMBI  ACETAS— LEAD  ACETATE.  U.S. 

Sugar  of  lead  occurs  in  transparent,  acicular,  often  aggregated,  crys- 
tals, of  a  sweet,  styptic  taste.  It  is  soluble  in  water,  to  which  it  usually 

*  Bardenhewer  affirms  that  pilocarpine  given  hypodermically  will  relieve  simultane- 
ously the  pulse  and  the  colic. 


422  GENERAL   REMEDIES. 

imparts  a  slight  milkiness.  From  its  solution  it  is  precipitated  black  by 
sulphuretted  hydrogen,  white  by  soluble  carbonates,  chlorides,  and  sul- 
phates, and  bright  yellow  by  potassium  iodide.  It  is  also  incompatible 
with  the  mucilage  of  slippery  elm,  but  scarcely  so  with  that  of  flaxseed 
or  of  pith  of  sassafras. 

THERAPEUTICS. — A  solution  of  lead  acetate  is  used  very  largely 
in  acute  external  inflammations  as  a  sedative  and  astringent  lotion. 
Although  chemically  incompatible,  it  is  frequently  combined  very  ad- 
vantageously in  these  cases  with  opium.  As  a  too  concentrated  solution 
acts  as  an  irritant,  the  strength  for  use  on  the  skin  should  not  exceed  ten 
grains  to  the  ounce.  In  diseases  of  the  eye  it  is  condemned  by  oculists, 
because  when  there  is  any  abrasion  of  the  cornea  it  is  very  prone  to 
deposit  an  opaque  film. 

Internally,  lead  acetate  has  been  employed  very  largely  in  hemor- 
rhage ;  indeed,  George  B.  Wood M  commends  it  as  the  most  valuable  of 
all  astringents  in  hemoptysis.  We  think  it  is  now,  however,  rarely  given 
for  this  purpose.  Its  chief  use  at  present  is  in  diarrhoea.  On  account  of 
its  sedative  properties,  when  the  purging  is  attended  by  inflammation  it 
is  the  most  serviceable  of  all  the  astringents  ;  and,  owing  to  the  prompt- 
ness of  its  action,  it  is  also  very  valuable  in  cases  with  profuse  serous 
discharges.  Dose,  two  to  five  grains  (0.13-0.32  Gm. ),  in  pill,  repeated 
pro  re  nata. 

LIQUOR  PLUMBI  SUBACETATIS.  U.  S. — The  Solution  of  Lead  Subace- 
tate,  or  Goulard' s  Extract,  as  it  is  sometimes  called,  is  a  colorless  limpid 
liquid,  of  a  sweetish,  astringent  taste.  When  exposed  to  the  air,  it 
rapidly  absorbs  carbonic  acid  and  deposits  lead  carbonate,  the  neutral 
acetate  being  left  in  solution.  In  its  action  upon  the  human  organism, 
Goulard's  extract  resembles  very  closely  the  simple  lead  acetate  ;  but 
it  is  never  used  internally.  Externally,  it  is  a  favorite  application  in  cases 
of  sprains  or  bruises,  as  well  as  in  superficial  inflammation.  For  this 
purpose  it  requires  dilution,  and  from  a  fluidounce  to  four  fluidounces 
of  it  may  be  added  to  a  pint  of  water.  When  used  upon  a  raw  surface, 
the  strength  should  not  be  so  great.  The  Diluted  Solution  (  LIQUOR 
PLUMBI  SUBACETATIS  DILUTUS,  U.  S.,  strength  four  per  cent.)  is  too 
weak  to  be  of  value. 

PLUMBI  CARBONAS,  or  Lead  Carbonate,  is  a  heavy,  white,  tasteless 
powder,  insoluble  in  distilled  water,  but  slightly  soluble  in  water  contain- 
ing carbonic  acid.  It  is  used  solely  as  an  external  sedative  application. 
Rubbed  up  with  linseed  oil,  it  constitutes  white  lead  paint,  and  in  this 
form,  or  in  that  of  the  ointment  (UNGUENTUM  PLUMBI  CARBON ATIS,  U. 
S.  1890),  it  is  a  most  efficient  dressing  for  fresh  burns.  Care  must  be 
taken  in  its  use,  however,  when  a  large  surface  is  involved,  as  lead  colic 
has  been  caused  by  its  absorption. 


ASTRINGENTS.  423 

PLUMBI  NITRAS,  U.  S.,  or  Lead  Nitrate,  occurs  in  white,  nearly 
opaque,  octahedral,  very  heavy  crystals,  soluble  in  two  parts  of  water 
at  59°  F. ,  and  in  o.  75  part  of  boiling  water  ;  almost  insoluble  in  alcohol. 
It  is  used  chiefly  as  a  disinfectant.  Dissolved  in  water,  it  forms  Le- 
doyeri  s  Disinfectant  Solution.  It  acts  by  decomposing  the  sulphuretted 
hydrogen,  itself  being  converted  into  a  lead  sulphide.  It  is  said  to 
attack  actively  the  soldering  of  pipes.61  Lead  nitrate  is  frequently  used 
in  onychia  maligna.  The  dead  part  of  the  nail  should  be  cut  away,  and 
the  powdered  nitrate  thickly  sprinkled  over  the  surface  ;  after  a  few 
days  the  slough  separates,  leaving  a  clean  surface,  upon  which  the  new 
nail  usually  soon  forms.  Sometimes  more  than  one  application  of  the 
remedy  is  required. 

BISMUTHUM— BISMUTH. 

The  metal  bismuth  is  never  used  in  medicine  in  its  simple  or  metallic 
form.  BISMUTHI  SUBCARBONAS,  U.  S. — BISMUTH  SUBCARBONATE, 
U.  S. ,  a  white  or  yellowish-white  powder,  tasteless  and  odorless,  totally 
insoluble  in  water,  soluble  with  effervescence  in  dilute  nitric  acid,  contains 
not  less  than  fifty-two  per  cent,  of  bismuth  oxide  ;  BISMUTHI  SUBNITRAS, 
or  BISMUTH  SUBNITRATE,  U.  S. ,  a  heavy  white  powder,  odorless,  with  a 
faint  acid  taste,  and  a  decidedly  acid  reaction  when  applied  to  moistened 
litmus-paper,  almost  insoluble  in  water,  soluble  without  effervescence  in 
nitric  acid,  contains  not  less  than  eighty  per  cent,  of  bismuth  oxide.  The 
complicated  official  processes  for  the  making  of  salts  were  designed  to 
get  rid  of  the  arsenic,  which  contaminates  all  the  bismuth  ores  of  Europe. 
Of  late  years  the  South  American  bismuth  has  been  introduced  into  com- 
merce, and,  as  it  contains  no  arsenic  commercial  bismuth  preparations 
are  now  pure. 

PHYSIOLOGICAL  ACTION. — The  actions  of  bismuth  subcarbonate  and 
subnitrate  are  so  exactly  similar  that  they  can  practically  be  considered 
as  one.  Orfila  and  others  of  the  older  observers  attributed  to  bismuth 
violent  irritant  properties,  reporting  severe  symptoms  and  even  death 
after  its  ingestion.  These  results  were,  however,  due  not  to  the  bismuth, 
but  to  the  arsenic  with  which  it  was  contaminated.  The  soluble  prepa- 
rations of  bismuth  are,  it  is  true,  active  irritant  poisons  (see  BISMUTHI 
CITRAS),  but  the  insoluble  subcarbonate  and  subnitrate,  when  pure,  have 
practically  no  irritant  influence.  It  was  formerly  denied  that  they  are 
dissolved  at  all  in  the  alimentary  canal,  but  it  is  now  certain  that  they  are 
very  slowly  absorbed  and  as  slowly  eliminated.  Harnack  *  affirms  that 
the  metal  has  been  found  by  Orfila  in  the  liver,  spleen,  and  urine,  and  by 
Lewald  in  the  milk.  Bergeret  and  Mayen9on  ~  state  that  when  bismuth 
subnitrate  is  administered  the  metal  can  always  be  detected,  after  a  few 
hours,  in  the  urine.  They  have  also  discovered  it  in  the  serous  exuda- 
tion of  dropsy,  and  have  proved  that  when  a  few  grains  of  the  salt  men- 
tioned are  given  to  rabbits,  in  from  twenty  to  thirty  minutes  it  can  be 
found  in  the  urine,  kidneys,  spleen,  blood,  and  muscles,  and  even  eight 
days  after  the  administration  can  be  detected  in  all  the  tissues.  Five 


424  GENERAL  REMEDIES. 

days  after  the  exhibition  of  a  gramme  of  the  subnitrate  to  a  man  they 
found  traces  of  the  metal  in  the  liver  and  kidneys  ;  but  the  analysis  of 
the  body  of  a  woman  dead  sixty-two  days  after  the  ingestion  of  two 
grammes  yielded  negative  results.  E.  S.  Wood 3  also  has  detected  bis- 
muth in  the  urine  four  weeks  after  its  last  exhibition. 

The  discovery  by  Theodore  Kocher 4  that  the  most  insoluble  bismuth 
preparations  are  actively  antiseptic  led  to  their  use  in  surgery,  and  to  the 
further  discovery  that  when  applied  in  very  large  quantities  to  extensive 
wounded  surfaces  they  are  capable  of  yielding  so  much  bismuth  to 
absorption  as  to  produce  a  poisoning,  which  is  characterized  by  acute 
stomatitis,  sometimes  gangrenous,  with  a  peculiar  black  discoloration  of 
the  mucous  membrane,  usually  beginning  upon  the  borders  of  the  teeth, 
but  spreading  over  the  whole  mouth,  followed  by  an  intestinal  catarrh 
with  pain  and  diarrhoea,  and  in  severe  cases  with  desquamative  nephritis, 
as  shown  by  albuminous  urine  and  epithelial  tube-casts.* 

That  bismuth  is  capable  of  acting  as  a  poison  in  the  lower  animals  has  been 
abundantly  proved  by  the  experiments  of  F.  Balzer  5  and  of  P.  Dalchd  and  E.  Ville- 
jean,6  which  show  that,  whether  given  by  the  mouth  or  hypodermically,  repeated 
large  doses  of  it  produce  gradual  failure  of  strength,  a  peculiar  stomatitis,  and  evi- 
dences of  gastro-intestinal  irritation,  with  death  from  exhaustion.  Balzer  states 
that  the  stomatitis  which  it  causes  differs  from  the  stomatitis  of  ptyalism  in  the 
tendency  to  rapid  gangrenous  change  ;  and  also  that  the  bismuth  is  eliminated  with 
the  saliva,  bile,  and  urine,  but  has  a  distinct  tendency  to  accumulate  in  the  tissues. 

THERAPEUTICS. — It  is  stated  (by  means  of  the  Roentgen  rays  in  the 
living  animal,-and  by  means  of  the  microscope  in  animals  killed)  that  after  the 
administration  of  bismuth,  it  maybe  demonstrated  that  the  insoluble  prep- 
arations of  bismuth  gradually  spread  themselves  over  the  gastro-intestinal 
mucous  membrane,  and  undergo  slow  conversion  into  the  black  oxide  of 
bismuth,  f  Experimental  science,  therefore,  is  in  accord  with  the  con- 
clusion previously  reached  by  clinicians,  that  by  virtue  of  their  physical 
and  chemical  properties  these  bismuth  preparations  act  as  protectives  to 
the  mucous  membrane,  and  especially  by  their  slow  change  and  absorp- 
tion not  only  exert  an  antiseptic  influence,  but  have  a  peculiar  persistent 
sedative,  astringent  action.  They  are,  therefore,  of  great  service  in  the 
treatment  of  irritations  and  inflammations  of  those  mucous  membranes 
with  which  they  can  be  brought  in  contact.  Thus,  they  are  useful  to 
allay  vomiting  dependent  upon  gastric  irritation.  In  simple  neuralgic 
gastric  pain  following  eating,  especially  when  occurring  in  feeble,  badly 
nourished  subjects,  bismuth  is  often  of  great  service  ;  and  even  in  car- 
cinoma it  may  palliate  by  alleviating  pain  and  vomiting.  In  Pyrosis  it  is 
sometimes  successful  ;  in  gastric  and  enteric  catarrhs  it  is  a  standard 
remedy.  In  the  simple  diarrhoea  of  irritation  and  in  the  chronic  diarrhoea 
of  camps  the  bismuth  preparations  are  often  very  efficient  ;  and  in  the 
chronic  bowel  complaints  of  children,  especially  as  seen  in  the  summer 

*  For  cases,  see  Kocher,  also  Petersen  (Deutsches  Med.  Wochcnschr.,  June  20,  1883). 
t  Consult  Cenlralblall f.  innere  Medizin,  1894,  S.  2.     Also,  Inaug.  Dis.,  Jena,  1893. 


ASTRINGENTS.  425 

season,  given  with  pepsin,  they  are  almost  invaluable.  Bismuth  is  a  very 
serviceable  topical  remedy  in  the  treatment  of  mucous  inflammations  and 
of  ulcers  to  which  it  can  be  applied  directly.  Thus,  in  the  beginning  of  a 
gonorrhoea,  the  injection  every  two  hours  of  a  mixture  containing  thirty 
grains  of  bismuth  to  the  ounce  usually  brings  immediate  relief ;  in  a  simi- 
lar way  it  may  be  employed  in  leucorrkcca  and  in  acute  coryza.  In  Ger- 
many it  has  been  to  some  extent  used  as  a  surgical  dressing. 

ADMINISTRATION. — In  order  to  get  the  best  attainable  results  from 
the  use  of  bismuth  subnitrate  it  is  necessary  to  vary  the  dose  and  method 
of  administration.  In  stomachic  affections  from  five  to  fifteen  grains 
may  be  given  preferably  when  the  stomach  is  empty,  in  order  that  the 
bismuth  may  be  distributed  as  closely  as  possible  over  the  gastric  mucous 
membrane.  In  intestinal  diseases  from  fifteen  grains  to  a  drachm  (1-4 
Gm. )  may  be  exhibited  in  capsule  from  one  to  two  hours  after  meals  at  a 
time  when  the  gastric  contents  are  escaping  through  the  pylorus.  Chil- 
dren bear  proportionately  very  large  doses  :  thus,  five  to  ten  grains  may 
be  given  to  a  two-year-old  infant. 

BISMUTHI  CITRAS.  U.  S. — The  insoluble  bismuth  citrate  is  not  used 
in  medicine,  but  has  been  introduced  into  the  Pharmacopoeia  for  the  pro- 
duction of  the  soluble  BISMUTHI  ET  AMMONII  CITRAS,  U.  S.  We  know 
of  no  recorded  cases  of  poisoning  by  this  salt,  which,  however,  is  probably 
capable  of  acting  as  a  corrosive  poison. 

According  to  Feder-Meyer  *  the  Bismuth  and  Ammonium  Citrate  causes  in  rab* 
bits  violent  tremblings  with  diarrhoea,  accompanied  after  large  doses  by  disturbance 
of  the  sensibility  and  of  coordination,  tetanic  cramps,  altered  respiration  (in  the 
beginning  accelerated  and  superficial,  afterwards  becoming  slow),  continual  lower- 
ing of  the  blood-pressure,  and  death.  The  same  observer  noticed  in  chronic  poi- 
soning similar  symptoms  with  albuminous  urine  and  after  death  fatty  degeneration 
of  the  liver,  heart,  and  renal  secreting  structure.  Similar  observations  were  made 
by  Mory,8  who  states  that  the  death  in  mammals  is  the  result  of  cardiac  paralysis, 
and  that  in  the  advanced  stages  of  chronic  poisoning,  when  the  blood-pressure  is 
very  low,  it  is  not  elevated  by  stimulation  of  the  splanchnic  nerves  nor  by  asphyxia. 
W.  Steinfeld9  has  obtained  in  the  frog  from  the  administration  of  bismuth  ammonio- 
citrate  and  ammonio-  tartrate  peculiar  tremblings  of  the  voluntary  muscles  with 
prolongation  of  contraction  upon  stimulation  with  the  galvanic  current,  and  slow- 
ing of  the  heart's  beat,  also  after  sufficient  doses  paralysis  of  nerves  and  muscles  ; 
effects  which  he  attributes  not  to  the  bismuth,  but  to  the  acids  of  the  preparations. 
He  states  that  the  proper  symptoms  produced  by  the  metal  appear  only  after  some 
hours,  and  consist  of  motor  excitement  with  reflex  cries  which  are  due  to  irritation 
of  the  medulla  oblongata.  In  acutely  poisoned  mammals  he  noticed  vomiting  and 
purging,  convulsions  with  loss  of  power,  slowing  of  the  pulse,  and  sinking  of  the 
blood-pressure,  believed  by  him  to  be  all  of  centric  origin.  In  chronic  poisoning 
there  was  loss  of  certainty  of  movement  with  cardiac  depression  followed  by  in- 
creasing paralysis,  usually  ending  in  death  without  convulsions.  In  his  studies 
upon  absorption  and  elimination  he  found  that  the  ammonio-citrates  and  ammonio- 
tartrates  are  quickly  eliminated  through  the  kidneys,  so  that,  as  a  rule,  after  from  ten 
to  fifteen  hours  they  can  no  longer  be  found  in  the  blood,  tissues,  or  urine. 


426  GENERAL  REMEDIES. 

THERAPEUTICS. — The  ammonio-citrate  of  bismuth  in  small  dose  is 
actively  stimulant,  astringent,  and,  probably,  germicidal.  In  large  dose 
it  is  a  violent  irritant.  It  has  none  of  the  peculiar  properties  which  grow 
out  of  the  insolubility  of  the  subnitrate,  but  is  more  astringent,  and  has 
been  used  in  chronic  diarrhoea  and  in  the  acute  diarrhoeas  of  relaxation. 
Dose,  two  to  five  grains  (0.13-0.32  Gm. )  in  dilute  watery  solution,  re- 
peated every  three  to  six  hours  pro  re  nata. 

BISMUTH  OXYIODOGALLATE  or  AIROL  is  a  grayish-green,  non-irritating,  tasteless, 
odorless  powder,  containing  about  two  parts  of  bismuth  to  one  part  of  iodine.  When 
brought  in  contact  with  a  surgical  surface  it  turns  red  from  the  liberation  of  iodine. 
According  to  the  studies  of  Carl  S.  Haegler  it  is  in  its  bactericidal  properties  about 
equivalent  to  iodoform,  the  products  of  its  surgical  decomposition  being,  as  in  the  case 
of  that  drug,  active  germicides.  Injected  into  the  lower  animals  in  doses  of  from 
one  to  three  grammes  per  kilo,  it  causes  clonic  convulsions,  with  coma,  nephritis, 
and  fatty  degeneration  of  the  liver.  Theoretically  the  toxic  dose  should  produce 
the  combined  symptoms  of  iodine  and  bismuth-poisoning,  but  in  Haegler's  "  exper- 
iments the  symptoms  rather  resembled  those  caused  by  bismuth,  and  in  a  case 
reported  by  Aemmer,12  symptoms  of  bismuth-poisoning  followed  the  injection  into 
the  cavity  of  an  abscess  of  nine  and  one-half  fluid  drachms  of  the  ten  per  cent,  glyce- 
rin solution.  Haegler  took  fifteen  grains  of  airol  in  the  course  of  three  days  with- 
out the  production  of  any  disagreeable  symptoms.  It  has  been  largely  used  as  a 
substitute  for  iodoform  on  account  of  its  lack  of  odor.  It  may  be  employed  for  the 
making  of  antiseptic  gauze  or  similar  dressings,  or  applied  directly  as  a  dry  powder  ; 
as  a  salve  of  ten  to  twenty  per  cent,  with  lard  or  vaselin  free  from  water,  or  be  in- 
jected in  ten  per  cent,  glycerin  solution  in  tubercular  or  other  abscesses,  or  used  in 
the  form  of  suppositories  made  with  cacao-butter  in  metritis,  vaginitis,  etc.  Brun's 
Paste,  much  used  in  various  skin  diseases  and  ulcerations,  consists  of  airol  one  part, 
mucilage  and  glycerin  each  two  parts,  kaolin  sufficient  to  make  a  soft  paste. 

BISMUTHI  SUBGALLAS.  U.  S.  Bismuth  Subgallate.  Dermatol. — This  is  a  dry, 
yellowish-saffron  or  bright-yellow  powder,  odorless,  tasteless,  insoluble  in  ordinary 
menstruum,  containing  from  fifty-two  to  fifty-five  per  cent,  of  pure  bismuth  oxide. 
It  is  believed  by  many  practitioners  to  add  to  the  general  local  influence  of  the  in- 
soluble bismuth  preparations  the  astringent  powers  of  gallic  acid.  Originally  pre- 
pared by  Heintz  and  Liebreich 10  as  a  substitute  for  iodoform,  it  has  come  quite 
largely  into  use  in  the  treatment  of  eczema  and  other  skin  diseases  and  in  surgical 
dressings.  It  is  not,  however,  a  true  substitute  for  iodoform ;  is  but  a  very  feeble 
germicide,  and  both  externally  and  internally  acts  as  do  other  insoluble  preparations 
of  bismuth,  for  which  it  may  be  substituted  in  gastro-intestinal  diseases,  in  doses  of 
from  ten  to  thirty  grains  (1-2  Gm.). 

BISMUTHI  SUBSALICYLAS.  U.  S.  Bismuth  Subsalicylate. — A  whitish,  amor- 
phous or  crystalline,  odorless,  tasteless,  insoluble  powder,  containing  from  sixty-two 
to  sixty-four  per  cent,  of  bismuth  oxide.  It  has  been  much  used  in  diarrhoeas  under 
the  belief  that  it  is  slowly  decomposed  in  the  intestines  with  the  elimination  of 
salicylic  acid.  We  have  never  been  able  to  perceive  any  difference  between  its 
action  and  that  of  the  more  ordinary  insoluble  salts  of  the  metal.  Dose,  ten  to 
twenty  grains  (0.65-1.3  Gm.). 

CERII    OXALAS.     U.  S. 

Cerium  oxalate  of  the  U.  S.  Pharmacopoeia  is  a  white  powder,  insoluble 
in  water,  alcohol,  and  ether,  but  soluble  in  sulphuric  acid.  It  is  a  mixture  of 


ASTRINGENTS.  427 

the  oxalates  of  cerium,  didymium,  praesodymium,  lanthanum,  and  other 
rare  earths.  It  has  been  employed  in  medicine  quite  largely  for  the  relief 
of  vomiting,  especially  when  dependent  upon  pregnancy  or  other  forms  of 
uterine  disturbance.  Its  action  on  the  economy  has  not  yet  been  made 
out,  but  it  may  be  tried  with  some  hope  of  success  in  cases  of  nervous  or 
dyspeptic  vomiting.  The  dose  is  one  to  three  grains  (0.06-0.19  Gm.), 
in  pill,  three  or  four  times  a  day. 

ZINCUM— ZINC. 

ZINCI  SULPHAS — Zinc  Sulphate.  U.S. —  White  Vitriol  occurs  in 
irregular  white  masses,  the  pure  zinc  sulphate  in  minute,  transparent, 
four-sided,  prismatic  crystals,  which  effloresce  slightly  in  dry  air,  and  are 
soluble  in  0.6  part  of  water  at  59°  F. ,  and  in  0.2  part  of  boiling  water, 
also  soluble  in  about  three  parts  of  glycerin  ;  insoluble  in  alcohol.  The 
taste  is  styptic  and  peculiar. 

THERAPEUTICS. — Zinc  sulphate  is  in  weak  solution  a  stimulant  as- 
tringent, in  concentrated  form  an  active  irritant.  Emetic  dose,  thirty 
grains  (2  Gm. ).  In  doses  of  one  grain  (0.06  Gm. ),  it  has  been  given 
in  pills  as  a  stimulant  astringent  in  chronic  diarrhoea  with  ulceration. 

TOXICOLOGY. — Zinc  sulphate  in  large  doses  acts  as  an  irritant  poison, 
producing  violent  vomiting,  colicky  pains,  diarrhoea,  prostration,  etc. 
The  symptoms  which  it  causes  are  almost  identical  with  those  produced 
by  the  corresponding  salt  of  copper.  Alkalies  and  their  carbonates  are 
the  chemical  antidotes  to  it,  producing  insoluble  precipitates.  Eggs  and 
milk  should  also  be  exhibited,  and  the  symptoms  treated  as  they  arise. 
Chronic  zinc-poisoning,  if  it  really  exists  at  all,  is  very  rare,  and  the 
metal  seems  to  be  used  with  impunity  in  cooking-utensils. 

Schlockow1  affirms  that  zinc-smelters  rarely  live  to  be  over  forty-five  years 
of  age,  dying  sometimes  of  catarrh  of  the  bronchial  or  alimentary  mucous  mem- 
branes, or,  in  other  cases,  of  a  peculiar  nervous  affection,  which  commences  with 
burning  superficial  pains,  exalted  sensibility,  and  reflex  activity  in  the  legs,  and 
afterwards  puts  on  still  more  clearly  the  features  of  myelitis  ;  and  A.  Sacher  *  finds 
that  intravenous  injection  of  very  large  doses  of  zinc  salts  produces  paralysis  of 
the  voluntary  muscles. 

ZINCI  OXIDUM  VENALE. — Commercial  zinc  oxide  is  a  snow-white 
powder,  obtained  by  burning  the  metal  in  the  air.  It  should  be  used 
only  in  pharmacy.  The  pure  oxide  (  ZINCI  OXIDUM,  U.  S. )  is  a  yellow- 
ish-white powder,  insoluble  in  water,  but  soluble  without  effervescence  in 
dilute  acids. 

THERAPEUTICS. — Zinc  oxide  is  used  externally  as  a  mildly  astringent, 
slightly  stimulant,  and  desiccant  application  in  skin  diseases  and  to  ulcers. 
When  given  continuously  in  small  doses  it  is  believed  to  act  as  a  tonic 
and  alterative  upon  the  nervous  system.  It  has  also  been  commended  as 
an  astringent  in  chronic  catarrhal  diarrhoea  of  adults  and  infants,  and  has 
been  largely  used  in  epilepsy  and  in  chorea.  Dose,  one-half  to  two  grains 


428  GENERAL  REMEDIES. 

(0.03-0.12  Gm.).     The  ointment  (UNGUENTUM  ZINCI  OXIDI,  U.  S.,— 
one  part  to  four  of  benzoinated  lard)  is  useful  in  various  skin  diseases. 

ZINCI  CARBONAS  PR^CIPITATUS.  U.S. — Precipitated  zinc  carbonate 
is  intended  to  replace  the  old  impure  native  carbonate,  calamine.  It  is 
made  by. precipitating  the  zinc  sulphate  by  the  sodium  carbonate.  It  is 
a  white  powder,  closely  resembling  in  its  medical  properities  zinc  oxide. 

ZINCI  ACETAS.  U.  S. — Zinc  acetate  occurs  in  white,  micaceous  crystals,  which 
effloresce  in  a  dry  atmosphere  and  are  very  soluble  in  water.  The  taste  is  astrin- 
gent and  metallic.  The  zinc  acetate  resembles  in  its  physiological  and  therapeutic 
qualities  the  sulphate,  but  is  probably  somewhat  less  active.  It  is  chiefly  used  in 
collyria  (one  to  two  grains  to  one  fluidounce),  and  as  an  injection  (one  to  twenty 
grains  to  one  fluidounce)  in  gonorrhoea. 

ZINCI  BROMIDUM.  U.  S. — This  is  a  white  deliquescent  powder  of  a  saline  me- 
tallic taste.  In  full  doses  it  is  an  irritant  emetic  but  has  been  chiefly  used  in  epi- 
lepsy. Its  value  is  doubtful.  Dose  one  to  two  grains  (0.06-0.13  Gm) . 

CUPRUM— COPPER. 
CUPRI  SULPHAS— COPPER  SULPHATE.  U.S. 

Copper  sulphate  occurs  in  blue,  transparent,  slightly  efflorescent, 
rhomboidal  prisms,  or  their  fragments.  It  dissolves,  at  59°  F. ,  in  about 
2.6  parts  of  water  and  in  0.5  part  of  boiling  water  ;  almost  insoluble  in 
alcohol.  With  ammonia  its  solution  precipitates  a  bluish-white  cupric 
hydrate,  which  redissolves  when  an  excess  of  the  alkali  is  added,  forming 
a  rich  deep  blue  solution. 

PHYSIOLOGICAL  ACTION. — In  very  dilute  solution  the  copper  sul- 
phate acts  locally  as  a  stimulant  and  mild  astringent ;  in  a  more  concen- 
trated form  it  is  an  irritant ;  in  powder  it  is  a  very  mild  caustic,  which  is 
scarcely  capable  of  destroying  sound  tissue.  The  salts  of  copper  in  suf- 
ficient amount  are  poisonous  to  all  forms  of  protoplasm.  Coupin  T  found 
that  0.0055  Per  cent,  solution  of  soluble  salt  of  copper  will  prevent  ger- 
mination of  wheat  :  that  copper  compounds  affect  violently  the  genera] 
nutrition  in  animals  is  shown  by  the  production  of  fatty  degeneration  by 
them  (see  Ellenberger  and  Hofmeister).  According  to  Falck,2  the  cupric 
sulphate  causes  in  the  lower  animals  great  depression  of  temperature, 
with  progressive  general  paresis,  ending  in  death,  apparently  from  failure 
of  respiration.  When  the  copper  salt  was  given  hypodermically,  vomiting 
was  not  produced  ;  although  when  it  was  exhibited  by  the  mouth,  emesis 
was  very  violent  and  persistent. 

THERAPEUTICS. — Cupric  sulphate  is  occasionally  used  for  its  local 
effect  in  chronic  enteritis  and  colitis,  with  ulceration,  but  is  rarely  of  value. 
It  was  at  one  time  much  employed  in  the  treatment  of  organic  nervous 
diseases,  but  has  fallen  into  deserved  desuetude.  Forty  years  ago  Men- 
dini  recommended  it  in  the  treatment  of  chlorosis  with  amenorrhcea,  a  use 
which  has  been  revived  from  time  to  time  and  has  recently  been  com- 


ASTRINGENTS.  429 

mended  by  Liegeois. 13  A.  F.  Price 15  claims  that  cupric  sulphate  in  doses 
of  one-thirtieth  of  a  grain  three  times  a  day  greatly  enhances  the  power 
of  the  mercurials  in  syphilis.  Dose,  one-eighth  to  one-quarter  of  a  grain 
(0.008-0.016  Gm. )  in  pill. 

The  chief  value  of  the  so-called  blue  stone  is  as  an  external  appli- 
cation. When  applied  in  solid  form  to  ulcers,  it  destroys  flabby  granu- 
lations and  exerts  a  powerful  excitant  influence.  Its  solution  acts  more 
feebly,  and  is  sometimes  employed  as  a  dressing  for  indolent  idcers,  but 
more  frequently  as  a  stimulant  and  alterant  to  mucous  membranes,  as  in 
granular  conjunctivitis  and  urethritis. 

In  1904  Moore  and  Kellerman  of  the  U.  S.  Department  of  Agriculture 
stated  that  copper  sulphate  even  in  minute  quantities  is  capable  of  destroy- 
ing both  algae  and  typhoid  bacilli.  According  to  Gildersleeve w  i  part 
in  1,000,000  is  sufficient  to  kill  all  typhoid  germs  in  water  in  three  hours 
although  other  microorganisms  seem  more  resistant.  This  property  de- 
pends probably  on  the  disassociation  of  the  ions,  for  metallic  copper 
seems  to  be  more  efficient  than  any  of  its  salts.  Stewart "  found  that 
water  inoculated  with  typhoid  bacilli  and  kept  in  copper  vessels  contained 
none  of  these  organisms  after  three  hours  and  comparatively  few  of  the 
other  forms  of  bacteria,  and  Kraemer 18  has  shown  that  copper  foil  placed 
in  the  water  has  the  same  effect.  It  does  not  seem  probable  that  the 
minute  quantity  of  copper  present  in  these  circumstances  (about  i  part 
to  4,000,000)  can  exercise  any  very  deleterious  effect  on  the  system 
especially  as  much  of  it  becomes  united  with  the  organic  matters  and  pre- 
cipitated. When  large  amounts  of  foreign  substances  are  present  in  the 
water  copper  is  so  much  less  efficient  in  its  germicidal  powers,  that  accord- 
ing to  both  Fowler 19  and  Doty 20  it  is  of  no  Tactical  value. 

TOXICOLOGY. — The  symptoms  of  acute  copper-poisoning  generally 
come  on  in  about  a  quarter  of  an  hour,  but  may  be  postponed  for  from 
one  to  two  hours.  They  consist  of  violent  vomiting  and  purging,  accom- 
panied by  very  severe  colicky  pains.  The  matters  vomited  are  greenish 
or  bluish,  the  stools  glairy,  mucous,  and  at  times  bloody.  There  is  a 
very  strong  taste  of  copper  in  the  mouth,  and  often  constant  expectora- 
tion ;  excessive  salivation  and  bronchial  secretion  are  stated  by  Galippe  * 
to  be  characteristic.  Death  may  occur  in  a  few  hours,  preceded  by  con- 
vulsions, paralysis,  delirium,  anaesthesia,  and  other  symptoms  of  great 
nervous  disturbance,  seemingly  as  the  result  of  a  direct  action  of  the  poi- 
son upon  the  nervous  system.  Sometimes  a  tendency  to  syncope  is  very 
marked,  and  as  both  L.  Schwarz*  and  W.  Filehne 5  have  found  that  toxic 
doses  of  copper  salts  paralyze  the  heart  in  the  lower  animals,  cardiai 
death  probably  occurs  in  human  poisoning.  The  urine  is  usually  les- 
sened or  suppressed.  Black  urine,  due  to  the  presence  of  haemoglobin 
without  unaltered  blood- corpuscles,  has  been  noted  ;  in  this  case,  after 
death  all  the  tissues  were  found  stained  with  altered  blood,  and  evidently 
destruction  of  the  blood  was  an  important  factor  in  the  fatal  result  ; 6 
fatty  degeneration  of  the  liver  was  also  found.  If  the  patient  survives 


430  GENERAL   REMEDIES. 

for  twenty-four  hours,  jaundice  nearly  always  shows  itself.  After  this, 
profound  depression  with  nervous  symptoms  may  develop  and  end  in 
death  ;  but  not  rarely  a  favorable  issue  results,  in  which  case  the  symp- 
toms of  gastro-intestinal  inflammation  with  fever  develop  themselves. 
The  copper  is  said  to  be  eliminated  more  freely  with  the  salivary  and 
intestinal  secretions  than  with  the  urine  (Galippe). 

As  the  action  of  the  cupric  sulphate  is  exceedingly  rapid,  any  anti- 
dote to  be  of  avail  must  be  given  at  once  and  act  quickly.  In  the  poi- 
soning milk,  eggs,  or  other  albuminous  substance  should  be  exhibited  im- 
mediately, freely,  and  repeatedly.*  Soap  or  a  fixed  alkali  may  be  used. 
The  yellow  prussiate  of  potash,  when  pure,  is  harmless,  and  precipitates 
instantly  an  insoluble  compound  of  copper  from  solutions  of  its  salt. 
When  it  is  to  be  had  in  time,  it  may  therefore  be  used  as  an  antidote  to 
the  sulphate.  The  treatment  of  copper-poisoning  after  the  administration 
of  the  antidote  consists  in  meeting  the  indications  as  they  arise  ;  opium 
should  be  used  freely.  When  death  occurs,  the  results  of  gastro-intes- 
tinal inflammation  are  usually  found  ;  sometimes  the  intestine  has  a 
decided  bluish  tint,  and  occasionally  submucous  ecchymoses  occur.  In 
exceptional  cases,  it  is  said,  there  are  no  evidences  of  inflammation  in 
the  alimentary  canal,  f  Fatty  degeneration  of  the  liver  has  been  noted 
in  man. 

There  has  been  much  discussion  as  to  whether  there  is  or  is  not  a 
chronic  copper  poisoning  among  workers  in  that  metal.  The  chief  symp- 
toms which  have  been  described  as  present  are  coppery  taste  in  the 
mouth,  gastro-intestinal  irritation  with  pain,  anaemia,  progressive  emacia- 
tion, cough,  and  nervous  disturbances  with  tremors.  The  green  discolor- 
ation upon  the  gums  or  teeth,  which  was  first  pointed  out  by  Clapton,7 
has  been  noted  by  Taylor,  by  the  Committee  of  the  London  Clinical 
Society,8  and  various  other  observers.  It  is,  however,  not  constant,  and 
may  exist  in  persons  who  show  no  other  evidences  of  poisoning.  Accord- 
ing to  Kurth,12  it  really  consists  of  a  greenish  or  olive  discoloration  on  the 
front  of  the  teeth,  and  is  due  to  the  staining  of  the  tartar,  since  when  the 
teeth  are  perfectly  clean  there  is  no  staining.  It  is  probable  that  most,  if 
not  all,  of  the  symptoms  of  the  chronic  poisoning  noted  in  workers  in 
copper  are  due  to  the  local  action  of  the  copper  dust  upon  the  various 
mucous  membranes,  an  explanation  which  is  rendered  more  probable  by 
the  fact  pointed  out  by  Kurth,  and  also  by  Lewin,14  that  workers  in 
copper  often  have  their  hair  colored  green. 

*  No  time  should  be  lost  in  attempting  to  separate  the  yolk  from  the  white  of  the  egg, 
but  the  egg  should  be  broken  into  a  bowl  as  quickly  as  possible,  a  little  water  added,  and 
the  whole  stirred  up  and  exhibited. 

t  For  a  fatal  case  of  repeated  poisoning  by  copper,  with  much  information  of  value  to 
chemical  experts,  see  La  France  Mid.,  September,  1874,  abstracted  in  Half- Yearly  Com- 
pendium, January,  1875.  Bournevette  and  Yvon  (Revue  Scienttfique,  1874,  859)  found  two 
hundred  and  ninety-five  milligrammes  of  metallic  copper  in  the  liver  of  a  woman  who 
had  taken  the  ammoniacal  sulphate  three  months  previously.  Minute  quantities  of  cop- 
per exist  in  the  normal  human  body  (Bull.  Therafi.,  xciii.  88). 


ASTRINGENTS.  431 

When  copper  is  given  to  the  lower  animals  in  continuous  sufficient  dose  it  pro- 
duces loss  of  appetite,  failure  of  digestion,  diarrhoea,  and  other  evidences  of  gas- 
tro-intestinal  catarrh  ;  with  marked  evidences  of  disturbances  of  the  nutrition,  such 
as  emaciation,  failure  of  the  heart,  and  with  a  progressive  paralysis  and  failing  respi- 
ration ending  in  death.  After  death  alterations  of  the  blood  and  wide-spread 
fatty  degeneration  have  been  noted  by  numerous  observers.*  According  to  Von 
B6kay,9  the  muscles  are  very  early  affected,  cloudiness  of  their  protoplasm  and 
disappearance  of  their  cross-striation  coming  on.  The  liver  and  kidneys,  how- 
ever, are  especially  attacked :  in  the  beginning  there  are  hyperplasia  of  the  con- 
nective tissue  and  subacute  nephritis,  followed  by  fatty  degeneration  and  finally 
atrophy. 

Although  Galippe  and  Burcy  and  also  Ducom  10  affirm  that  copper  is 
almost  without  influence  upon  dogs,  and  Galippe "  fed  himself  for  one 
month  on  food  containing  a  large  amount  of  copper  without  causing 
any  symptoms  of  intoxication,  it  is  certain  that  whilst  very  minute  quan- 
tities of  copper  may  be  taken  internally  habitually  without  producing 
injury,  larger  doses  may  slowly  and  insidiously  work  out  fatal  conse- 
quences. The  matter  is  important  because  the  metal  is  habitually  used 
in  the  canning  of  vegetables,  French  peas,  beans,  etc. ,  owing  their  at- 
tractive color  to  their  treatment  with  copper,  which  can  be  chemically 
recognized  in  them. 

The  possibility  of  injury  from  such  food  has  been  repeatedly  investigated  by 
French  and  Belgian  commissions,  and  the  general  verdict  has  been  that  no  harm  is 
produced.  The  fact  that  twenty  millions  of  cans  of  these  food-articles  are  con- 
sumed every  year,  and  that  after  thirty-six  years'  continuance  of  the  custom  it  has 
not  been  clearly  established  that  harm  is  done,  indicates  that  in  the  amount  used 
the  vegetables  containing  copper  are  not  poisonous.  It  is  plain  that  the  freedom 
from  injury  depends  upon  the  minuteness  of  the  amount  of  copper  ingested  ;  the 
Italian  law  does  not  allow  more  than  0.05  gramme  of  copper  per  kilo  of  food,  but 
the  researches  of  Tschirch  would  indicate  that  a  food  containing  this  amount  of 
copper,  if  very  freely  taken,  might  do  harm.t 

ARGENTUM— SILVER. 

ARGENTI    NITRAS— SILVER    NITRATE.     U.S. 

This  is  a  heavy  anhydrous  salt,  crystallizing  in  translucent,  shining, 
rhombic  plates,  and  having  a  styptic,  metallic,  corrosive  taste.  It  is  solu- 
ble, at  59°  F.,  in  0.6  part  of  water,  in  twenty-six  parts  of  alcohol,  in  o.  i 
part  of  boiling  water,  and  in  five  parts  of  boiling  alcohol.  For  external 
use  the  crystals  are  melted  and  run  into  moulds,  where  they  harden  into 
round,  grayish,  brittle  sticks,  about  the  size  of  a  goose-quill,  and  having 
a  radiated  crystalline  fracture.  These  constitute  the  official  ARGENTI 
NITRAS  Fusus.  As  only  the  pure  salt  will  make  well-formed  crystals,  the 

*  Falck  (Deutsch,  Klinik,  1859,  xi-)>  Ellenberger  and  Von  Hofmeister  (Arch.Wissen. 
Prakt.  Thierheilk.,  x.  228),  W.  Filehne  (Deutsch.  Med.  Wochen.,  1893,  xxi.),  De  Moor, 
Von  B6kay  (Pester  Med.-Chir.  Presse,  1897,  33),  Baum  and  Seeliger  (Archivf.  Thier- 
heilk., 1897,  xxiii.,  1898,  xxiv.),  and  Trolldenier  (Archivf.  Thierheilk.,  1897,  xxiii. 

t  For  discussion  upon  the  subject,  see  De  Moor  (Archives  de  Pharmacodynamie, 
1895,  i.)  and  Tschirch  (  Toxicologie  und  Hygiene,  Stuttgart,  1893). 


432  GENERAL  REMEDIES. 

impure  products  are  always  manufactured  into  the  fused  nitrate,  which 
should  therefore  not  be  employed  internally.  When  silver  nitrate,  either 
in  substance  or  in  solution,  is  exposed  to  the  conjoint  influence  of  light 
and  of  even  a  minute  portion  of  organic  matter,  it  turns  black,  and  is 
converted  into  an  insoluble  substance,  which  has  been  believed  to  be 
metallic  silver,  but  is  more  probably  an  oxide.  For  this  reason  the  white 
stains  which  it  first  makes  when  applied  to  living  tissues  soon  blacken. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Silver  nitrate  coagulates 
albumin,  and,  when  applied  in  its  pure  state  to  living  tissues,  acts  as  a 
caustic,  coating  them  over  with  a  white  almost  membranous  film.  The 
caustic  action  is,  however,  not  a  deep  one,  because  penetration  of  the 
salt  into  the  tissues  is  soon  prevented  by  the  thick  and  tough  skin  or 
stratum  which  is  formed.  When  applied  in  a  dilute  solution  it  acts  as 
an  astringent,  constringing  the  vessels  and  overcoming  relaxation.  Its 
local  action,  however,  is  not  simply  that  of  an  astringent,  but  is  certainly 
peculiar  and  apparently  alterative  to  nutrition.  It  is  also  a  very  active 
germicide. 

Absorption  and  Elimination. — It  is  evident  that  in  the  stomach  sil- 
ver nitrate  cannot  long  maintain  its  integrity.  Bogolowsky '  has  found 
that  when  the  nitrate  is  added  to  a  peptone  it  is  readily  dissolved,  and 
that  the  solution  formed  does  not  coagulate  albumin.*  That  in  this  or 
in  some  other  analogous  form  silver  is  absorbed  is  proved  by  its  having 
been  found  in  various  internal  organs  and  by  the  discoloration  which 
follows  its  protracted  use  :  argyria  of  authors.  When  it  is  exhibited 
for  a  long  continuous  period,  the  skin  often  acquires  a  peculiar  bluish 
slate  color,  which  may  become  very  dark,  and  in  decided  cases  the 
conjunctiva  and  even  the  mucous  membrane  of  the  mouth  are  involved. 
The  silver  is  found  in  all  the  tissues  of  the  skin  below  the  rete  Malpighii  f 
(Frommann,2  Riemer,3  Neumann4).  E.  Harnack5  asserts  that  in  all 
recorded  cases  of  argyria  at  least  thirty  grammes  of  the  salt  have  been 
taken.  The  staining  of  the  skin  is  always  preceded  by  a  dark  discolor- 
ation of  the  mucous  membrane  of  the  mouth  and  gums.  Both  Heller 
and  Orfila  failed  to  detect  silver  in  the  urine  of  animals  taking  it  ;  but 
probably  it  is  eliminated,  though  slowly  and  in  very  small  quantities,  by 
the  kidneys. 

General  Effects. — As  silver  is  never  given  for  an  immediate  therapeu- 
tic action,  its  acute  physiological  action  is  of  less  interest  to  the  therapeu- 

*  For  recent  studies  of  this  character,  see  Isidore  Neumann  (loc.  cit.),  also  A.  von 
Fragstein  (Berlin.  Klin.  U'ochen.,  1877,  294). 

t  In  an  elaborate  study  of  the  organs  of  a  case  of  argyria,  Riemer  detected  the  silver 
in  the  glomerules  of  the  kidney,  the  intima  of  the  aorta,  the  choroid  plexus,  and  the  mesen- 
teric  glands.  He  believes  that  it  is  never  deposited  inside  the  cells,  and  that  the  silver 
preparation  is  reduced  in  the  intestines,  and  the  fine  particles  of  the  silver  carried  in  the 
blood  and  lymph.  Gerschun  (Arbeiten  aus  Physiolog.  Inst.zu  Dorpat,  x.)  coincides 
with  Riemer  in  affirming  that  the  silver  is  deposited  outside  of  the  cells,  but  O.  Loew 
(Pfi tiger's  Archil',  xxxiv.  603)  asserts  that  it  occurs  inside  of  the  renal  endothelial  cells. 
Jahn  (Beitrdge  z.  Patholog.  Anal.,  xvi.)  states  that  the  unstriated  muscular  fibres  and 
the  elastic  tissue  have  a  special  power  of  reducing  silver. 


ASTRINGENTS.  433 

tist  than  to  the  toxicologist,  and  the  detailed  symptoms  of  its  poisoning 
are  considered  under  the  head  of  toxicology.  In  general  these  symptoms 
consist  of  those  of  gastro-enteritis  with  violent  disturbance  of  the  nervous 
system,  due  to  a  direct  action  of  the  poison  upon  the  cerebrum  and  the 
spinal  cord.*  Although  the  circulation  is  profoundly  affected,  death  ap- 
pears to  take  place  from  centric  paralysis  of  respiration. 

By  an  elaborate  series  of  experiments  Charles  Rouget 6  has  shown  that  upon  all 
animals  from  a  crab  to  a  dog  the  soluble  salts  of  silver  act  as  a  poison,  causing  in 
mammals  vomiting  and  purging,  and  in  them  and  the  lower  animals  violent  dis- 
turbance of  the  motor  functions,  as  shown  by  paralysis  and  convulsions,  and  of  the 
respiration,  ending  finally  in  death  by  asphyxia.  This  is  in  accord  with  the  obser- 
vations of  other  investigators.  Rabuteau  and  Mourier  affirm  that  the  almost  instan- 
taneous death  which  Charcot  and  Ball  first  noted  as  following  the  injection  of  a  large 
dose  of  silver  nitrate  into  the  veins  is  due  to  a  direct  paralyzing  influence  of  the 
drug  upon  the  muscle  of  the  heart.  Rouget  has  never  seen  this  form  of  death 
follow  the  hypodermic  or  internal  administration  of  the  poison,  the  heart  always 
continuing  to  beat  for  a  greater  or  less  length  of  time  after  the  cessation  of  respira- 
tion, and  also  retaining  its  irritability. 

As  already  stated,  both  convulsions  and  paralysis  are  present  in  acute  silver- 
poisoning.  The  convulsions  are  severe,  generally  tetanic,  and  according  to  Rouget 
are  plainly  reflex.  A  peculiarity  noted  by  Rouget  is  the  persistence  of  the  convul- 
sions after  the  complete  abolition  of  voluntary  movements.  Curci 7  affirms  that 
they  are  due  to  excitation  of  the  motor  tract  of  the  cord,  and  that  this  is  preceded 
by  a  similar  influence  upon  the  sensory  tracts. 

The  death  is  due,  in  argyria,  to  cessation  of  the  respiration  ;  Rouget  even  states 
that  he  has  witnessed  the  suspension  of  the  latter  function  in  the  frog  while  the 
activity  of  the  reflex  movements  was  much  beyond  normal.  In  the  dog  and  in  the 
full-grown  cat  this  asphyxia  is  accompanied  by  an  outpouring  of  mucus  in  the  lungs, 
pulmonary  congestion  and  oedema  being  found  on  post-mortem  examination.  Two 
theories  have  been  propounded  as  to  the  cause  of  the  asphyxia  :  one,  that  it  is 
simply  due  to  the  choking  up  of  the  lungs  by  the  congestion  and  the  excessive 
secretion  whose  origin  is  an  altered  state  of  the  blood ;  a  second,  that  both  the 
asphyxia  and  the  lesions  in  the  lungs  have  their  origin  in  a  direct  action  of  the 
poison  upon  the  nerve-centres. 

The  first  view  has  been  especially  supported  by  Krahmer  and  by  Rabuteau  and 
Mourier.  Unfortunately,  we  have  not  seen  the  original  papers  of  these  physicians  ; 
but,  according  to  Rouget,  the  basis  of  the  argument  of  Krahmer  is  simply  the  ecchy- 
moses  which  he  found  in  horses  dead  of  the  poison,  while  that  of  Rabuteau  and 
Mourier  is  the  fluidity  of  the  blood  after  death,  and  the  existence  in  it  of  granules 
which,  on  account  of  their  solubility  in  ammonia,  were  believed  to  be  silver  chlo- 
ride. The  French  observers  were,  however,  almost  certainly  mistaken  in  their 
belief  that  these  granules  were  silver  chloride,  since  ammonia  dissolves  haematin 
as  freely  as  it  does  the  chloride. 

In  1864  Charcot  and  Ball 8  made  a  series  of  experiments  in  which  a  silver  salt 
that  did  not  coagulate  albumin  was  injected  directly  into  the  blood.  They  noted 
not  only  the  respiratory  embarrassment,  but  also  that  the  hinder  extremities  were 
suddenly  paralyzed,  and  concluded  that  both  the  asphyxia  and  the  lung  trouble 
were  due  to  an  affection  of  the  central  nervous  system.  In  1869  Bogolowsky,  of 

*  Orfila  and  other  of  the  earlier  observers  experimented  upon  it  by  injecting  it  directly 
into  the  veins  of  animals.  When  exhibited  in  this  way,  it  must,  by  coagulating  the  albu- 
min of  the  blood,  produce  thrombi,  to  which  the  subsequent  symptoms  are  in  greater  or 
less  measure  to  be  ascribed.  This  method  of  experimentation  can,  therefore,  throw  but 
little  light  upon  the  action  of  silver  nitrate  when  taken  into  the  stomach. 

28 


434  GENERAL  REMEDIES. 

Moscow,  studied  the  action  of  a  peptone  of  the  nitrate  when  used  hypodermically. 
He  found,  on  examination  of  the  blood  of  a  poisoned  animal,  that  the  spectrum 
analysis  betrayed  nothing  abnormal ;  that  the  red  corpuscles  appeared  paler  and 
their  outline  more  delicate  than  normal ;  and  that  the  white  corpuscles  were  natural. 
On  the  other  hand,  Rouget  examined  microscopically  the  blood  of  animals  poisoned 
with  silver  nitrate,  and  found  it  perfectly  normal.  The  only  conclusion  to  be  drawn 
from  all  this  seems  to  us  to  be  that  at  present  there  is  no  proof  whatever  that 
the  symptoms  of  acute  silver-poisoning  are  due  to  alterations  in  the  blood  :  that  the 
embarrassment  of  respiration  is  not  due  to  local  lesions  in  the  lungs  is  abundantly 
shown  by  the  experiments  of  Rouget,  who  found  that  while  in  all  animals  these 
respiratory  symptoms  are  very  prominent,  in  only  a  few  species  are  decided  pul- 
monic  lesions  found  after  death.  From  all  these  facts  we  think  it  highly  probable,  if 
not  altogether  certain,  that  the  theory  propounded  by  Charcot  and  Ball  is  correct. 
That  the  motor  disturbance  is  centric,  not  peripheral,  in  its  origin  is  shown  by  the 
fact  noted  by  Rouget,  that  the  muscles  and  nerves  preserve  their  excitability  after 
the  arrest  of  the  respiration. 

We  know  of  very  few,  if  any,  cases  of  chronic  poisoning  with  silver 
salts  in  man  (see  foot-note,  page  437);  the  following  summary  epitomizes 
the  results  of  chronic  poisoning  in  the  lower  animals. 

The  action  of  the  drug  when  exhibited  continuously  for  a  length  of  time  in 
large  doses  has  been  investigated  by  Bogolowsky  upon  dogs  and  rabbits.  He 
found  that  it  produced  loss  of  appetite,  wasting,  slight  lowering  of  bodily  tempera- 
ture, diarrhcea,  diminution  of  the  quantity  of  urine  passed,  with  increase  of  its 
specific  gravity  and  often  with  the  presence  of  albumin,  and  transitory  paralysis. 
How  far  some  of  these  symptoms  were  due  to  the  direct  constitutional  action  of 
the  poison  and  how  far  to  derangement  of  the  digestion  dependent  upon  its  local 
influence  is  perhaps  an  open  question.  The  local  action  was  avoided,  however,  as 
much  as  possible,  by  the  use  of  an  albuminate  or  of  the  double  phosphate  of  silver 
and  sodium,  which  does  not  coagulate  albumin.  Comparative  examinations  of  the 
blood  showed  that  the  haemoglobin  was  diminished  by  more  than  one-third.  The 
blood  was  also  rendered  very  aplastic,  as  was  betrayed  by  the  constant  tendency  to 
the  formation  of  ecchymoses.  As  some  one  has  suggested  that  the  silver  in  these 
cases  replaces  the  iron  of  the  blood-corpuscles,  Bogolowsky  made  a  chemical  ex- 
amination of  the  latter,  but  failed  to  find  any  traces  of  silver  in  them, — no  doubt 
because  it  was  not  there.  The  solid  tissues  were  found,  after  death  from  chronic 
argyria,  to  be  in  an  advanced  stage  of  degeneration,  which  especially  affected 
epithelial  structures.  The  first  change  was  swelling  and  opacity  of  the  cells,  with 
obscuration  of  the  nucleus.  After  this  came  fatty  degeneration,  fatty  globules  in 
the  cell,  destruction  of  nucleus,  and  finally  of  the  cell  itself.  The  liver  and  kidneys 
were  profoundly  influenced,  as  was  also  the  muscular  structure,  especially  of  the 
heart.  These  results  obtained  by  Bogolowsky  have  been  in  the  main  corroborated 
by  A.  V.  R6zsahegzi.9 

THERAPEUTICS. — The  results  of  the  chronic  poisoning  by  silver  are 
in  every  way  so  closely  analogous  to  those  produced  by  antimony,  arsenic, 
copper,  and  other  metallic  poisons  as  to  show  that  silver  belongs  to  that 
class  of  drugs  which  in  some  way  markedly  affects  the  general  nutrition. 
It  cannot,  however,  be  called  an  alterative,  as  at  present  we  know  of  no 
application  of  its  power  to  the  needs  of  practical  medicine. 

The  only  advantageous  use  of  silver  in  therapeutics  is  for  its  local 
action  either  upon  the  surface  of  the  body  or  upon  those  mucous  mem- 
branes that  can  be  reached  directly  by  the  drug. 


ASTRINGENTS.  435 

As  a  simple  caustic,  the  salt  may  be  used  whenever  a  superficial 
action  only  is  required  :  for  reasons  already  given  (page  432),  it  is  use- 
less whenever  it  is  necessary  to  produce  a  deep  eschar.  As  a  caustic 
alterative,  it  is  applied  in  solid  form  to  many  ulcerated  surfaces,  for  the 
purpose  of  destroying  superficial  diseased  tissue  and  of  substituting, 
when  the  eschar  separates,  a  healthy  for  an  unhealthy  action.  As  an 
antiphlogistic,  silver  nitrate  acts  not  only  as  an  astringent,  but  also  as 
a  germicide.  In  the  various  inflammations  of  the  mucous  membranes, 
such  as  conjunctivitis,  faucitis,  laryngitis,  urethritis,  etc. ,  it  is  used  very 
frequently,  not  only  in  the  stage  of  relaxation,  but  also  in  the  beginning 
of  the  attack.  In  conjunctivitis,  the  solution  employed  should  not,  under 
ordinary  circumstances,  be  stronger  than  one  or  two  grains  to  the  ounce  ; 
and  it  should  not  be  used  at  all  if  any  corneal  ulceration  exists,  since  a 
deposit  of  silver  is  liable  to  occur  and  to  produce  opacity.  In  faucitis, 
the  strength  of  the  solution  may  vary  from  thirty  to  sixty  grains  to  the 
fluidounce.  In  ordinary  cases  of  sore  throat,  the  application  once  a  day 
or  every  alternate  day  is  generally  sufficient.  It  is  best  made  by  means 
of  a  good-sized  camel' s-hair  brush,  each  part  of  the  inflamed  surface 
being  distinctly  touched,  and  not  the  whole  simply  daubed  or  slopped 
over  by  means  of  a  very  large  brush  or  a  sponge  probang.  In  severe 
cases  it  may  be  necessary  to  use  the  solution  twice  a  day.  Even  a  satu- 
rated solution  can  scarcely  be  looked  upon  as  caustic  to  the  more  robust 
mucous  membranes. 

Carl  Seller J0  states  that  while  solutions  of  silver  nitrate  of  less  than  sixty  grains 
to  the  ounce  cause  pain  when  applied  to  the  throat,  solutions  of  one  hundred  and 
twenty  to  two  hundred  and  fifty  grains  act  as  local  anaesthetics,  relieving  soreness, 
and  usually  arresting  acute  inflammations  at  once,  if  applied  in  the  first  twenty-four 
hours,  before  inflammatory  exudation  has  occurred. 

In  laryngitis,  the  solution  may  contain  from  ten  to  twenty  grains  to 
the  ounce,  and  should  be  applied  with  a  brush  by  the  aid  of  the  laryngo- 
scopic  mirror.  An  attack  of  urethritis  may  sometimes  be  aborted  in  its 
forming  stage  by  the  injection  of  a  strong  solution  (twelve  grains  to  one 
fluidounce)  of  the  salt  ;  but  the  practice  is  of  doubtful  expediency,  since 
when  it  fails  it  greatly  aggravates  the  trouble.  When  chronic  gonorrhoea 
is  strictly  localized  to  a  small  spot  in  the  posterior  urethra,  installation 
of  from  five  to  ten  minims  of  a  solution  of  the  strength  of  five  to  ten 
grains  to  the  fluidounce  is  often  serviceable.  When  the  inflammation  is 
more  diffused,  irrigation  with  a  weaker  solution  is  preferable  ;  at  first  i  to 
5000  may  be  employed,  and  the  strength  gradually  increased  to  even 
i  to  500. 

Freely  applied  to  the  skin  of  the  whole  finger,  silver  nitrate  will  some- 
times abort  a  commencing  felon,  or,  applied  to  the  scrotum,  an  epididy- 
•mitis. 

Internally,  silver  nitrate  is  exceedingly  useful  in  stomachic  and  to  a 
less  extent  in  enteric  diseases,  exerting  no  doubt  a  purely  local  influence. 


436  GENERAL  REMEDIES. 

In  that  form  of  dyspepsia  characterized  by  the  vomiting  of  large  quanti- 
ties of  yeasty  fluid,  it  has  yielded  in  our  hands  better  results  than  any 
other  remedy  ;  and  the  same  may  be  said  of  chronic  gastritis  and  of  gas- 
tric idcer.  The  rules  of  administration  are  identical  in  these  three  dis- 
eases. In  the  first  place,  regulation  of  the  diet  is  imperative  :  if  the  case 
be  a  bad  one,  all  eating  of  meals  should  be  suspended,  and  the  patient 
receive  every  two  or  three  hours  a  cup  of  sweet  milk,  with  sound 
toasted  bread  broken  up  and  thoroughly  softened  in  it.  In  order  to 
wash  off  as  much  as  possible  the  mucous  membrane  of  the  stomach, 
and  to  neutralize  the  acids  of  the  stomach,  forty-five  minutes  before 
the  meal  fifteen  to  twenty  grains  of  sodium  bicarbonate  should  be  ex- 
hibited in  a  tumblerful  of  hot  water,  and  ten  minutes  later  a  quarter  of 
a  grain  of  silver  nitrate  should  be  given  in  pill  form.  The  use  of  cold 
water  at  meals  should  be  absolutely  forbidden,  and  in  very  serious 
cases,  when  all  food  is  rejected  by  the  stomach,  it  is  sometimes  advisable 
to  allow  absolute  rest  for  two  or  three  days  to  that  viscus,  the  patient 
being  fed  by  the  rectum,  and  only  a  little  water  and  pills  of  silver  with 
opium  being  taken  by  the  mouth.  Under  these  circumstances,,  the 
return  to  the  usual  method  of  taking  food  must  be  very  gradual,  at  first 
only  a  tablespoonful  each  of  milk  and  of  lime-water  being  administered 
every  hour.  In  chronic  enteritis  or  colitis,  silver  nitrate  is  sometimes  of 
service,  especially  if  there  be  ulceration. 

For  its  constitutional  effects  silver  nitrate  is  used  solely  in  diseases  of 
the  nervous  system.  It  was  formerly  given  in  epilepsy,  but  it  has  passed 
out  of  use.  In  chronic  inflammations  of  the  spinal  cord,  whether  affect- 
ing chiefly  the  posterior  columns  and  constituting  locomotor  ataxia,  or  the 
anterior  and  giving  rise  to  paraplegia,  it  is  still  employed,  but  is  of  doubt- 
ful value. 

TOXICOLOGY. — The  symptoms  produced  by  the  ingestion  of  large 
doses  of  silver  nitrate  are  partly  gastro-intestinal  and  partly  cerebro- 
spinal.  In  some  instances  the  one  series  of  phenomena  predominate,  in 
others  those  of  the  other  class.  In  a  case11  at  the  Hopital  St. -Louis 
in  1839  the  symptoms  were  insensibility,  violent  convulsions,  dilated 
pupils,  and,  when  consciousness  was  partially  regained,  intense  gastric 
pain  :  complete  restoration  of  consciousness  did  not  occur  until  eleven 
hours  after  admission,  and  the  coma  returned  at  intervals  during  several 
days. 

Vertigo,  coma,  convulsions,  great  muscular  weakness,  and  paralysis, 
with  intense  disturbance  of  respiration,  are  in  these  cases  the  manifesta- 
tions of  disturbed  innervation,  whilst  the  abdominal  symptoms  are  those 
of  gastro-enteritis.  The  diagnosis  can  generally  be  made  by  the  discolor- 
ations  of  the  lips  and  skin — at  first  white,  afterwards  black — and  by 
the  blackish  or  brownish  vomit ;  when  the  customary  antidote  has  been 
given,  both  vomit  and  stools  are  generally  white  and  curdy.  After 
death  the  stomach  and  bowels  are  found  corroded,  often  ecchymbsed 
and  with  patches  of  a  white  or  grayish  color.  Poisoning  by  silver  nitrate 


ASTRINGENTS.  437 

is  not  common,  and  we  know  of  but  three  fatal  cases, — one  in  1837 
(Taylor"),  one  in  1861,  a  woman  killed  by  fifty  grains  in  solution  in  di- 
vided doses,  and  one  in  1871,  a  child  destroyed  by  a  piece  of  the  solid 
stick  three-quarters  of  an  inch  long,  in  spite  of  the  use  of  the  antidote 
(Scattergood13). 

The  treatment  consists  in  the  administration  at  once  of  large  amounts 
of  common  salt,  alkaline  carbonates,  or  soap, — the  chemical  antidotes, — 
the  constant  use  of  large  draughts  of  milk,  and  the  meeting  of  symptoms 
as  they  arise. 

The  fatal  dose  of  silver  varies  very  much,  according,  no  doubt,  to  the 
presence  of  substances  capable  of  decomposing  it  in  the  stomach.  Thirty 
grains  have  killed,  and  recovery  has  taken  place  after  the  ingestion  of 
an  ounce  (case,  Husemann14). 

Chronic  argyria,  or  discoloration  of  the  skin  by  silver,  is  usually 
unaccompanied  by  disturbances  of  health,  although  in  severe  cases  the 
discoloration  affects  not  only  the  skin,  lips,  gums,  and  sclerotic,  but  even 
the  internal  organs,  such  as  the  liver,  spleen,  and  kidneys.  It  is  there- 
fore not  due,  as  has  been  thought,  to  the  silver  chloride,  since  the  latter 
becomes  dark  only  under  the  influence  of  the  light,  but  to  a  deposition  of 
silver  itself  or  of  its  oxide.* 

S.  Krysinski 15  found  the  granules  in  almost  every  tissue  of  the  body,  and  states 
that  they  are  an  organic  compound  of  silver,  the  exact  nature  of  which  has  not  yet 
been  determined.  The  minute  quantity  of  the  metal  present  is  shown  by  the 
analysis  of  Versmanns,16  who  in  14.1  grammes  of  dried  liver  found  only  0.0068 
gramme  of  metallic  silver  (0.047  Per  cent.),  and  in  8.6  grammes  of  dried  kidney 
0.053  gramme  (0.61  per  cent.).  Greater  or  less  success  has  been  asserted  for 
various  treatments  in  argyria,  but  in  general  they  are  equally  futile. 

Rogers  states  that  blistering  will  lighten  the  color  very  much,  and 
Eichmann  asserts  (Husemann)  that  he  has  cured  two  cases  by  the  use  of 
potash  baths  and  of  soap  baths,  each  four  times  a  week.  The  older  au- 
thorities commend  the  use  of  potassium  iodide  internally.  L.  P.  Yan- 
dell17  has  reported  two  cases  in  which  large  doses  of  the  iodide  were 
given  for  many  months  for  syphilis,  and  the  mercurial  vapor-baths  used 
at  the  same  time  for  the  same  purpose,  with  the  result  of  a  complete  cure 
of  the  argyria.  The  fading  was  gradual. 

ADMINISTRATION. — The  silver  nitrate  should  always  be  given  in  pill, 
and,  when  it  is  desired  to  obtain  its  constitutional  influence,  after  meals, 
during  the  process  of  digestion  ;  but  when  its  local  action  on  the  stomach 
is  required,  it  should  be  administered  one  or  two  hours  before  meals  ; 
and  if  the  intestines  are  to  be  reached,  the  pill  should  be  enclosed  in  two 
thick  capsules.  The  administration  of  silver  nitrate  should  not  extend 
over  a  longer  time  than  two  months  without  a  protracted  intermission. 
The  dose  is  one-quarter  of  a  grain  (0.016  Gm. ). 

*  According  to  R6zsahegzi,  Hermann  has  seen  one  case  in  which  preceding  the  dep- 
osition of  the  silver  there  were  malaise,  emaciation,  failure  of  memory,  singing  in  the 
ears,  -deafness,  and  spasms  of  the  ocular  muscles. 


438  GENERAL   REMEDIES. 

ARGENTI  NITRAS  DILUTUS,  U.  S. ,  is  a  white  or  grayish,  solid  sub- 
stance, often  in  crayons,  composed  of  two  parts  of  potassium  nitrate  with 
one  part  of  silver  nitrate.  It  may  be  used  as  a  very  mild  caustic. 

Silver  Oxide.  (ARGENTI  OXIDUM,  U.  S. )  An  olive-brown  powder, 
very  slightly  soluble  in  water  ;  has  no  other  local  action  than  that  of  a 
very  feeble  astringent,  but  has  been  commended  in  pyrosis  in  doses  of 
a  grain  (o.  6  Gm. )  in  pill,  three  times  a  day,  on  an  empty  stomach.  It 
was  originally  incorrectly  affirmed  that  it  is  incapable  of  producing  chronic 
argyria,  and  that  it  is  therefore  superior  to  the  nitrate  in  chronic  nervous 
diseases,  in  which  diseases  it  is,  however,  valueless. 

Silver  Cyanide  (ARGENTI  CYANIDUM,  U.  S. )  is  used  solely  for  the 
preparation  of  hydrocyanic  acid.  Silver  iodide,  formerly  official,  has  been 
used  as  an  alterative,  but  is  of  very  doubtful  value. 

A  large  number  of  preparations  of  silver  have  been  recently  proposed 
for  use  in  practical  medicine  but  have  not  yet  become  official.  The  most 
important  of  these  preparations  are  as  follows  : 

ALBARGIN.  Gelatose  Silver. — This  compound  of  silver  and  gelatose  is  a  yel- 
lowish, bulky  powder,  dissolving  readily  in  cold  or  warm  water,  and  containing 
fifteen  per  cent,  of  silver.  It  affects  albumin  slowly,  but  may  be  used  with  cocaine 
provided  the  double  solution  be  freshly  prepared  at  the  time  of  administration.  It 
should  be  kept  in  amber-colored  bottles.  It  was  introduced  by  Bornemann,23  to  be 
used  in  a  one  to  two  per  cent,  aqueous  solution  in  gonorrhoea. 

ARGENTI  ACETAS.  Silver  Acetate. — This  has  been  especially  recommended 
by  Zweifel M  in  a  one  per  cent,  solution  for  the  treatment  of  ophthalmia  in  new-born 
children. 

ARGENTI  CITRICUM.  SILVER  CITRATE.  Itrol. — A  dry,  odorless  powder,  solu- 
ble with  difficulty  in  water,  has  been  recommended  as  intensely  poisonous  to  the 
gonococcus  and  non-irritant  to  the  urethral  membrane.  The  injection  of  from 
i :  4000  to  i  :  8000  solution  is  said  to  produce  no  pain  even  in  acute  gonorrhoea,  and 
may  be  practised  four  times  a  day.  The  remedy  has  also  been  used  in  chronic 
cystitis. 

ARGENTI  LACTAS.  SILVER  LACTATE.  Actol. — This  substance  is  soluble  in 
fifteen  parts  of  water,  and  may  be  used  in  very  strong  or  saturated  solution  for  the 
disinfection  of  infected  wounds.  It  is  decomposed  at  the  point  of  application,  but  is 
said  to  form  soluble  compounds,  so  that  it  is  able  to  find  its  way  deeply  into  the 
tissues.  One  gramme  has  been  given  hypodermically  without  serious  symptoms, 
except  some  burning.  The  application  of  the  pure  powder  to  an  affected  surface 
is  asserted  to  produce  only  moderate  and  brief  pain. 

ARGENTOL. — A  yellowish  powder  which  readily  splits  up  into  oxyquinoline 
and  metallic  silver  ;  it  has  been  recommended  by  Cipriani  as  efficient,  in  diarrhoea, 
as  an  astringent,  intestinal  antiseptic  of  which  fifteen  grains  ( i  Gm. )  may  be  given 
safely  in  twenty-four  hours,  if  necessary.  It  has  also  been  used  surgically  in  the 
strength  of  i  to  300  to  1000. 

ARGYROL.  Silver  Vitellin. — This  albuminous  compound  of  silver  occurs  in 
dark-brown  hygroscopic  scales,  very  freely  soluble  in  water,  and  containing  about 
thirty  per  cent,  of  silver.  These  solutions  keep  well  and  are  not  irritant.  At  the 
time  of  this  writing  argyrol  is  probably  the  most  popular  of  all  the  recent  prepara- 


ASTRINGENTS.  439 

tions  of  silver  in  the  treatment  of  gonorrhceal  infections  of  all  kinds.  In  injections 
the  strength  of  the  solution  should  usually  be  from  one  to  five  per  cent.,  although 
on  occasion  stronger  solutions  are  usually  well  borne.  For  irrigation,  solutions  of 
i  :  2000  to  i  :  500  are  employed.  Even  the  stronger  solutions  are  said  not  to  pro- 
duce unpleasant  symptoms.  Argyrol  is  much  used  by  dentists  in  gingivitis  and 
mouth  infections. 

LARGIN.  —  This  compound  of  silver  and  albumen  is  a  whitish-gray  powder, 
soluble  to  about  ten  per  cent,  in  water,  freely  soluble  in  blood  serum,  not  precipi- 
tated by  albumen,  and  containing  n.i  per  cent,  of  silver.  It  has  great  penetrating 
power  when  brought  in  contact  with  tissue,  and  has  been  highly  praised  by  a 
number  of  German  clinicians  as  a  germicide  in  the  treatment  of  gonorrhoea  and 
other  infectious  inflammations.  It  is  said  to  be  pre-eminently  satisfactory  in  the 
gonorrhoea  of  women.  In  man,  one-quarter  to  one  per  cent,  solution,  gradually 
increased  to  two  per  cent.  ,  may  be  used.  In  women,  the  parts  should  be  irrigated 
with  the  one-half  to  one  per  cent,  solution,  after  which  a  five  per  cent,  largin  bougie 
may  be  held  in  position  by  a  cotton  plug  for  fifteen  minutes,  and  the  part  again 
irrigated  with  a  five  per  cent,  solution  of  largin.  This  treatment  should  be  repeated 
every  day  for  one  week,  subsequently  every  second  or  third  day  only.  In  infectious 
conjunctivitis  and  in  catarrhal  corneal  ulcers,  Welander  especially  commends  the 
use  of  gelatin  tablets  containing  one  per  cent,  of  largin. 

ARGENTI  SULPHOPHENAS.  Silver  Sulphocarbolate.  Silberol.  —  Introduced  by 
Zanardi  as  a  substitute  for  silver  nitrate,  this  substance  has  been  considerably  used 
in  gonorrhoea,  and  as  a  surgical  germicide,  especially  in  connection  with  the  eye. 
It  is  asserted  that  the  two  per  cent,  solution  is  well  borne  by  the  conjunctiva,  and 
that  when  used  as  a  substitute  for  silver  nitrate  silberol  must  be  employed  in  twice 
as  concentrated  a  solution. 


ARGENTUM  SOLUBILE.  Soluble  Silver.  Colloidal  Silver.  Collargol.— 
allotropic  form  of  silver,  discovered  by  M.  Carey  Lea19  in  1891,  occurs  as  a  bluish 
or  green-colored  mass.  It  makes  with  water  a  deep  red  solution,  which  is  precipi- 
tated by  the  addition  of  salt  solutions.  Soluble  silver  was  originally  employed  by 
Cred^  as  a  non-poisonous  germicide,  to  be  used  for  internal  medication  in  various 
affections,  such  as  septiccemia,  diphtheria,  and  tuberculosis.  At  first  he  exhibited  it 
by  inunctions,  forty-five  grains  at  one  time  for  the  adult,  but  later  gave  five  to  ten 
grammes  of  the  one  per  cent,  solution  hypodermically  or  intravenously..  Theharm- 
lessness  of  these  intravenous  injections  has  been  confirmed  by  Muller,"  who  also 
affirms  that  in  septic  diseases  collargol  may  be  given  with  as  much  trust  as  antitoxin 
in  diphtheria.  The  value  of  the  remedy  is,  however,  very  doubtful.  The  experi- 
ments of  George  Brunner  25  have  shown  that  collargol  is  precipitated  by  gelatin  or 
bouillon  ;  that  it  is  not  soluble  in  blood  serum  although  it  remains  dissolved  if  the 
solution  of  it  be  mixed  with  the  serum  ;  that  the  germicidal  properties  of  it  are  very 
feeble,  —  twelve  hours'  contact  with  the  one  per  cent,  solution  of  it  being  required  to 
kill  most  pathogenetic  bacteria  ;  that  when  given  subcutaneously  or  intravenously  it 
has  no  apparent  effect  upon  animals,  and  that  granules  of  silver  can  be  found  later 
at  the  places  of  injection  :  finally,  that  whether  given  with  infected  matter  or  in- 
jected after  the  material,  in  the  lower  animals  it  has  no  influence  over  the  processes 
of  infection  or  upon  the  bactericidal  power  of  the  blood.  The  chills  and  other 
constitutional  disturbances  which  were  formerly  produced  by  the  intravenous  injec- 
tions of  collargol  were  probably  due  to  the  presence  of  impurities  in  the  solutions 
used,  and  the  whole  drift  of  present  evidence  is  to  show  that  collargol  probably 
never  circulates  in  the  blood  to  any  extent,  and  that  it  is  physiologically  inert. 

ARGONIN.     Argentum  Casein.  —  An  albuminous  preparation  of  silver,  readily 
soluble  in  warm  or  albuminous  water,  has  been  highly  recommended  in  inflam- 


\44<>  GENERAL  REMEDIES. 

mations  due  to  gonococci.     Its  ten  per  cent,  solution  is  said  to  produce  no  pain  ; 
even  in  acute  cases  it  may  be  used  freely. 

ICHTHARGAN.  Silver-thio-hydrocarbo-sulphonate. — This  compound  of  silver 
and  ichthyol  contains  about  thirty  per  cent,  of  silver  and  fifteen  per  cent,  of  sulphur. 
It  is  a  brown  amorphous  powder,  readily  soluble  in  water,  glycerin,  and.  dilute 
alcohol,  but  insoluble  in  absolute  alcohol  ;  and  is  precipitated  from  its  solution  by 
sodium  chloride  and  albumin  ;  the  latter  precipitate,  however,  being  redissolved 
by  an  excess  of  albumin.  It  is  stated  to  add  to  its  germicidal  and  antiphlogistic 
influences  a  distinct  locally  anaesthetic  power. 

According  to  the  researches  of  Aufrecht,27  ichthargan  is  much  more  destructive 
to  gonorrhceal,  pyogenic,  diphtheritic  and  typhoid  germs  than  is  either  colloidal 
silver  or  protargol,  its  one  per  cent,  ointment  being  as  active  as  the  fifteen  per 
cent,  of  collargol.  According  to  H.  C.  Wood,  Jr.,28  this  preparation  does  not  differ 
essentially  in  its  physiological  action  from  the  ordinary  salts  of  silver.  When 
injected  into  a  vein  it  produces  a  fall  of  the  blood-pressure  from  cardiac  weakness. 
After  death  the  lungs  are  found  congested  and  filled  with  a  frothy  fluid.  In  the  frog 
it  acts  as  a  depressant  to  the  spinal  cord,  and  when  locally  applied  as  a  paralyzant 
to  muscle-tissue.  Both  Aufrecht  **  and  Wood,  Jr.,  have  found  that  ichthargan  is  much 
less  toxic  than  is  silver  nitrate.  According  to  the  former  it  requires  four  times  the 
fatal  dose  of  the  nitrate,  while  according  to  Wood,  Jr. ,  the  fatal  dose  of  the  nitrate  for 
the  frog  is  one-tenth  that  of  the  silver  ichthyolate. 

Ichthargan  is  being  very  largely  used  in  gonococcal  and  other  infective  diseases 
of  the  mucous  membranes  ;  also  in  various  infected  ulcerations  and  skin  diseases. 
It  has  been  especially  commended  in  various  forms  of  rhinitis,  tonsillitis,  laryngitis, 
and  other  affections,  chronic  and  acute,  of  the  upper  respiratory  mucous  membrane, 
either  applied  in  spray  of  the  glycerin  solution  varying  from  four  to  ten  per  cent. , 
or  less  freely  in  solutions  up  to  twenty  per  cent.  No  irritation  is  produced  except 
after  the  strongest  applications. 

The  strength  of  the  ichthargan  solution  varies  in  gonorrhoea  from  i  :  500  to 
i  :  3000  for  injections  ;  from  i  :  2000  to  i  :  5000  for  irrigation  ;  one  to  three  per  cent, 
in  instillations.  In  the  gonorrhoea  of  women  most  excellent  results  are  said  to 
follow  packing  the  vagina  with  tampons  saturated  with  a  solution  :  one  to  five  parts 
of  ichthargan,  five  of  water,  and  one  hundred  of  glycerin  ;  a  five  to  ten  per  cent, 
ointment  may  also  be  employed.  In  chancroids  the  powder  of  ichthargan,  full 
strength  or  diluted,  may  be  used.  In  trachoma,  gonorrhceal,  and  other  infective 
conjunctivitis,  the  one  to  three  per  cent,  solution  may  be  applied  with  a  brush  ; 
i  :  1000  used  as  a  wash.  In  eczema,  ulcerations,  phlegmons,  vaginitis,  and 
lymphangitis,  the  ointment,  varying  from  one  to  fifteen  per  cent.,  is  advised,  well 
rubbed  into  the  adjacent  thoroughly  cleansed  healthy  skin,  and  also  applied  directly 
to  the  affected  surface  if  it  be  exposed. 

Ichthargan  has  also  been  administered  internally  with  asserted  and  excellent 
results  for  the  relief  of  gastritis,  and  especially  of  gastric  ulcers.  Dose,  one- 
twentieth  to  one-eighth  of  a  grain  in  half  an  ounce  of  water  on  an  empty  stomach. 

Intravenously  ichthargan  has  been  used  experimentally  in  various  septic  dis- 
eases, such  as  septic  endocarditis,  septic&mia,  etc.  It  is  stated  that  injections  of 
o.oi  to  0.02  gramme  per  kilo  (one-sixth  to  one-third  grain  per  two  and  a  half 
pounds)  may  be  given  without  risk.  At  present  there  is  no  sufficient  evidence  as 
to  the  value  of  the  treatment. 

PROTARGOL. — The  chemical  combination  of  silver  and  protein  occurs  as  a  fine, 
yellowish  powder,  readily  soluble  in  cold  water.  Its  solution  is  precipitated  by 
albumen,  by  dilute  solutions  of  sodium  chloride,  or  by  dilute  acids  and  alkalies.  It 
is  said  to  contain  eight  per  cent,  of  metallic  silver,  and  was  originally  proposed  by 
Professor  Niesser  as  having  the  antiseptic  properties  of  the  silver  salts,  and  being 
able  to  penetrate  tissues  on  account  of  its  not  coagulating  albumen.  According  to 


ASTRINGENTS. 


441 


the  experiments  of  Petitjean,  Athanasion,  and  Comparesco,  the  injection  of  protargol 
into  the  jugular  vein  of  the  dog  produces  in  a  very  few  minutes  a  fatal  pulmonary 
oedema,  probably  due  to  deposition  of  silver  and  consequent  mechanical  obstruction. 
Protargol  has  been  much  used  in  gonorrhcca,  infective  conjunctivitis  of  various 
forms,  as  well  as  in  infected  wounds.  In  gonorrhoea  in  the  female,  one  to  two  per 
cent,  solutions  of  protargol  are  used  as  vaginal  douches,  and  the  half  per  cent, 
solution  injected  into  the  urethra.  When  the  neck  of  the  cavity  of  the  uterus  is 
affected  bougies  containing  five  per  cent,  of  protargol,  with  starch  and  gum,  are  intro- 
duced into  the  uterus.  Then  a  tampon  saturated  with  a  ten  per  cent,  protargol 
glycerin  is  placed  in  front  of  the  neck  ;  this  should  be  done  daily  for  a  week.  In 
acute  gonorrhoea  of  the  male,  injections  of  half  of  one  per  cent,  solution  may  be 
given  three  times  a  day,  the  strength  rapidly  increased  to  one  per  cent. ;  the  injec- 
tions to  be  held  in  the  urethra  from  five  to  thirty  minutes.  In  infected  wounds  a 
lengthened  application  of  the  five  per  cent,  solution  may  be  made,  or  the  powder 
itself  used  by  dusting,  or  a  ten  per  cent,  ointment  applied. 


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Nord,  1898,  ii. 

24.  MALASSEZ  .   .   .   .  A.  de  P.,  1874,  50. 

25.  HEUBEL Virchow      and      Hirsch's 

Jahrbiicher,  1871,  i.  316. 

26.  CHATIN C.  R.  S.  B.,  1862,  iv.  84. 

27.  ELLENBERGER  and  HOFMEISTER  .  Arch.      f. 

Wissen.  u.  Prakt.  Thier- 
heilk.,  x.  216. 

28.  PITT Trans.  Path.  Soc.,  London, 

1891,  xlii. 

29.  D£GERINE  .  .   .  .  C.  R.  S.  B.,  1880. 

30.  LANC£REAUX    .   .  Gaz.  M6d.  Paris,  1862 ;  1871. 

31.  WESTPHAL    .   .   .  Arch.  f.  Psychiatr.,  iv.  776. 

32.  FRIEDLXNDER  .   .  V.  A.  P.  A.,  Ixxv.  24. 

33.  BIRDSALL    .   .   .   .  N.  Y.  M.  R.,  March,  1882. 

34.  GOURBAULT   .   .   .  Prog.  M.,  1880. 

35.  DEBOVE  and  REAUT  .  Prog.  M.,  1876,  151. 

36.  VULPIAN Maladies    du    Syst.    Ner- 

veux,  1879. 

37.  MONAKOW  ....  Arch.  f.  Psychiat.,  x.  495. 

38.  OELLER Festschrifl       d.       Aerzll. 

Verein  Miinchen,  1883. 

39.  POPOW V.  A.  P.  A.,  xciii.  351. 

40.  GOURBAULT  .  .  .  A.  de  P.,  1873. 

41.  STIEGLITZ  ....  Arch.    f.    Psychialr.,   1892, 

xxiv. 

42.  SCHAFFER  ....  Ungar.  Arch.  f.  Med.,  1893, 

xi. 


442 


GENERAL   REMEDIES. 


REFERENCE 

4;.  SCHULTZE  ....  Arch.    f.   Psychiatr..    1885, 
xvi.  809.. 
44.                                    Prog.  M.,  xii.  827. 
45.  O'CARROLL    .  .   .  B.  M.  J.,  1893,  i. 
46.  FISHER    A.  J.  M.  S.,  189*.  civ. 
47.  MELSENS    .   .   .   .  Ann.  Phys.  et  Chim.,  xxv. 
48.  POUCHET    .  .   .   .  A.  de  P.,  xii.  74. 
49.  ANNUSCHAT  .  .  .  A.  E.  P.  P.,  x. 
50.  POUCHET    .  .   .   .  A.  de  P.,  1879. 
51.  ODDO  and  SILBERT  .  Rev.    de    M£d.,    Paris, 
1892,  xii. 

IS.  —  Continued. 
5.  FILEHNE     .   .   .   .  D.  M.  W.,  1893,  xxi. 
6.                                   N.  V.  M.  R.,  xxi.  567. 
7.  CLAPTON     .  .   .  .  M.  T.  G.,  June,  1868. 
8.  LONDON  CLINICAL   SOCIETY  .  Transactions 
1870,  13. 
9.  VON  BOKAY    ...  P.  M.  C.  P.,  1897,  33. 
10.  DUCOM      A.  de  P..  1877.  iv.  i8t. 

ii.  GALIPPE 

C.  R.  A.  S.  Ixxxiv  718. 

12.  KURTH     .   .   .   , 

13.    LlEGEOIS 

.  N.  Y.  M.  R.,  1900,  Iviii. 

14.  LEWIN      .   .   . 

D.  M.  W.,  1900,  xxvi. 

15.  PRICE   ..... 

.  N.  Y.  M.  R.,  1903. 

53.                                      L.  L.,  1876,  ii.  53. 
54.                                    Meyer's  Electricity,  N.  Y., 
1869,  284. 
55.  HARNACK                A.  E.  P.  P.,  1878. 

l6.   GlLDERSLEEVE 

17.  STEWART    .  . 
iv  KRAEMER  .  . 
19.  FOWLER      .  . 

.  A.  J.  M.  S.,  1905,  cxxix.  757. 
.   .  A.  J.  M.  S.,  cxxix.  761. 
.   .  A.  J.  Pharm.,  1906,  140. 
.   .  Journ.  Roy.  Army  Corps., 
v.  391. 
,   .  N.  Y.  M.  R.,  1905,  Ixvii.  90. 

56.  VON  WYSS              V.  A.  P.  A.,  xcii. 

5-    CURCI                        G  H   M  C    1883  552  •  Gaz 

d.  Ospitali,  March,  1883. 
58.  FRANK  D.  A.  K.  M.,  xvi.  422. 

i.  BOGOLOWSKY 
2.  FROMMANN    . 
3.  RIEMER 

SILVER. 
V.  A.  P   A     1869  xlvi  413 

59.  BARDENHEWKR    .  B.  K.  W.,  1877,  126. 
60.  WOOD  Therapeutics,  i.  158. 

.    .  V.  A.  P.  A.,  xvii.  135. 

61.                                     Report  on  Hygiene,  U.  S. 
Navy,  1879. 
62.  SABRAZESand  BOURRET  .  Cb.  I.  M.,  1902. 
63.  MORITZ    D.    M.    W.,    1901,    xxvii.; 

4.  NEUMANN  .   . 
5.  HARNACK    .   . 
6.  ROUGET  ... 

.    .  Medizin.    Jahrbiich.,   1877, 
369- 
.   .  Arzneimittellehre,        1883, 
410. 
.  A.  de  P.,  1873,  356. 

also  P.  M.  W.,  1901,  xviii. 
64.  RANSOM  B.  M.  J.,  1900,  i. 

65.  SAILER  J.  A.  M.  A.,  1905,  xliv.  1515. 
BISMUTH. 
i.  HARNACK    ....  Arzneimittellehre,        1883 
383- 
2.  BKRGERET  and   MAYKNCON  .  J.  A.   P.,   1873, 
242. 

8.  CHARCOT  and  f 

9.    RdzSAHEGZI   .     . 

10.  SEILER     .... 

IALL  .  Gaz.  Med.,  1864. 
.  A.  E.  P.  P.,  ix.  295. 

.  J.  A.  M.  S.,  i.  266. 

ii. 
12.  TAYLOR  .... 

13.  SCATTERGOOD  . 
14.  HUSEMANN    .   . 

15.  KRYSINSKI  .   . 

Beck's  Medical  Jurisprud., 
Phila.,  1863,  i.  675. 
.  Med.     Jurisprudence,     2d 
ed.,  1.319. 
.  B.  M.  J.,  May,  1871. 
.  Toxicologie,    Berlin,   1862, 
868. 
.   .  L.  M.  R.,  Aug.  16,  1886. 

Ass.,  1883,  23. 
4.  KOCHER                  Volkmann's      Klin      Vor- 

trage,  No.  224. 
5.  BALZER    C.  R.  S.  B.,  1889. 
6.  DALCHE  and  VILLEJEAN  .  B.  G.  T.,  1888,  Ivii. 
7.  FEDER-MEYER     .  In.  Dis.,  Wiirzburg,  1879. 

16.  VERSMANNS  .   . 
17.  YANDELL    .  . 
18. 
19.  LEA  

V.  A.  P.  A.    1859   xvii 

.   .  Amer.  Pract.,  June,  1872. 
P.  M.  T.,  vi.  204. 

.  Amer.  Journ.  Science,  1889, 

10.  HEINZ  and  LIEBREICH  .  G.  M.  P.,  1891. 
11.  HAEGLER    .   .   .   .  C.  B.  S.  A.,  1895. 
12.  AEMMER                  C  B.  S  A    1897  xxvi: 

20.  CREDK  

xxxvii.  479. 
.A.    K.    C..    1807.    Iv  •  also 

1903,  Ixix. 
21.  CHANEVANT  and   ROSTERNAK  .  C.   R.  S.  B., 
1903,  Iv. 

22.   NlESSER  .    .         .    -  T.  W..  1807. 

ZINC, 
i.  SCHLOCKOW  .   .   .  D.  M.  W.,  1879,  208. 
2.  SACHER    Thesis,  Dorpat,  1893. 

COPPER, 
i.  COUPIN    C.  R.  A.  S.,  1898,  cxxvii., 
400. 
2.  FALCK  D.  KL,  1859,  xi. 

23.    BORNEMANN   . 
24.    MC'LLER   .... 

25.  BRUNNER    .   .   . 

26.    ZWEIFEL       .     .     . 

27.  AUFRECHT  .   . 

28.  WOOD,  JR.  .  . 
29.  AUFRECHT  .   . 

30.  FALK    . 

.   .  Ther.  Geg.,  1901. 
.  D.  M.  W.,  1902. 
.  Fort.  M.,  1900,  xviii. 
.  Cb.  G.,  1900. 
.   .  Merck's    Annual    Report, 
1902. 
.   .  N.  Y.  M.  J.,  April,  1903. 
.   .  Deutsch.    Med.  Wochen., 
1900,  xxvi. 
.  T.  M..  1806.  x. 

3.  GALIPPE  Etude      toxicol.     sur     la 
Cuivre,  Paris,  1875. 
4.  SCHWARZ    .          .  A.  E.  P.  P..  iSos.  xxv. 

FAMILY   II.— TONICS. 


MINERAL   TONICS. 

FERRUM— IRON.     U.S. 

SINCE  iron  constitutes  a  necessary  integrant  portion  of  the  red  blood- 
corpuscles,  it  is  a  food  rather  than  a  medicine.  A  large  proportion  of 
the  various  articles  of  ordinary  diet  contain  a  trace  of  it,  and  it  must 
undoubtedly  find  entrance  with  the  food  into  the  blood.  Although  a 
great  amount  of  work  has  been  done  by  chemists  upon  the  absorption 
and  elimination  of  iron,  the  results  have  been  so  imperfect,  contradictory, 
and  difficult  of  explanation  that  they  are  at  present  of  very  little  use  to 
the  clinician.  Iron  is  probably  at  all  times  in  the  urine  in  minute  quan- 
tities. Among  the  older  chemists,  Quevenne  taught  that  the  exhibition 
of  the  salts  of  iron  had  little  influence  upon  the  amount  of  iron  in 
the  urine,  whilst  Becquerel  found  that  the  increased  elimination  of  iron 
commenced  directly  after  the  first  taking  of  a  ferruginous  preparation, 
and,  though  varying  notably  from  day  to  day,  continued  on  the  whole 
until  the  end.  Among  the  later  chemists,  Bunge,  of  Basel,  believes  that 
no  salts  of  iron  are  absorbed  into  the  blood,  and  that  the  value  of  the 
iron  in  chlorosis  is  due  to  its  local  action  on  the  gastric  juices.  His 
theory  is  that  in  chlorosis  there  is  a  great  poverty  of  gastric  juice,  with 
an  excessive  formation  of  alkaline  sulphides  ;  that  these  alkaline  sulphides 
decompose  the  absorbable  albuminous  iron  compounds  of  the  food,  and 
render  them,  like  ordinary  salts,  incapable  of  absorption  ;  and  that  the 
ordinary  iron  preparations  occupy  the  alkaline  sulphides,  and  allow  the 
albuminous  iron  compounds  to  be  absorbed. 

Bunge  bases  his  theory  upon  the  experimental  results  obtained  by  himself 
and  by  Hamburger,1  which  he  believes  prove,  first,  that  in  the  healthy  subject 
the  continued  administration  of  iron  does  not  raise  the  red  blood-corpuscles  or 
haemoglobin  ;  second,  that  when  iron  is  given  it  does  not  increase  the  amount  ex- 
creted in  the  urine.  The  researches  quoted  later  in  this  article  (page  416)  throw, 
however,  the  gravest  doubt  upon  the  theory  of  Bunge.  Moreover,  it  is  directly 
opposed  by  the  research  of  Carl  Th.  Moerner,2  who  finds  as  the  result  of  the  study 
of  urinary  indican,  etc.,  during  the  administration  of  iron,  no  reason  for  believing 
that  the  salts  of  iron  act  as  intestinal  antiseptics. 

The  researches  of  certain  Dorpat  investigators  and  of  Peter  Robert 
Berry,  epitomized  below,  would  also  appear  to  prove  that  the  Pharmaco- 

443 


444  GENERAL    REMEDIES. 

poeial  preparations  of  iron,  when  taken  into  the  organization,  are  not  ab- 
sorbed,— a  conclusion,  however,  which,  for  reasons  given  a  little  later, 
cannot  be  accepted. 

Nicolai  Damaskin,  Johann  Kumberg,  Chr.  Busch,  and  Eugen  Stender,  work- 
ing with  and  under  the  immediate  supervision  of  Robert,  of  Dorpat,  found,  first, 
that  the  presence  of  iron  can  be  demonstrated  in  normal  filtered  or  unfiltered  urine, 
both  quantitatively  and  qualitatively  ;  that  the  elimination  of  iron  does  not  cease,  as 
has  been  affirmed,  during  fasting  in  man  ;  and  that  the  administration  of  an  official 
preparation  of  iron  does  not  cause  iron  to  disappear  from  the  urine  :  second,  that 
the  iron  exists  in  the  urine  in  two  portions,  one  in  the  morphological  elements,  nor- 
mal and  pathological,  of  the  urine,  the  other  dissolved  in  the  urine  itself ;  it  being 
doubtful  whether  the  iron  is  or  is  not  simply  in  the  coloring-matter  of  the  urine,  but 
it  being  certain  that  this  iron  in  solution  is  in  some  very  permanent  combination,  as 
it  resists  even  heating  of  the  urine  with  muriatic  and  nitric  acids  :  third,  that  the 
normal  relation  of  the  iron  in  the  morphological  elements  to  that  in  solution  ap- 
pears to  be  from  one  to  seven  to  one  to  eight :  fourth,  that  the  daily  elimination  of 
iron  in  the  urine  is  scarcely  one  milligramme,  but  is  subject  to  much  variation,  ac- 
cording to  nourishment,  etc.  ;  in  sickness  attended  by  destruction  of  the  blood, 
or  with  increase  of  the  morphological  elements  of  the  urine,  the  elimination  of  the 
iron  increases,  but  the  presence  of  biliary  coloring-matter  in  the  urine  has  no  in- 
fluence upon  it :  fifth,  that  when  iron  and  sodium  citrate  is  injected  subcutaneously 
into  man,  in  the  dose  of  one  milligramme  per  seven  kilogrammes  of  weight,  forty 
per  cent,  of  the  iron  escapes  in  the  urine  unaltered,  such  injections  being,  however, 
attended  by  distinct  danger  of  renal  irritation,  so  that  hypodermic  injections  of 
iron  should  be  given  in  very  minute  doses  only  :  sixth,  that  the  administration  of 
the  ferrous  citrate  or  of  the  saccharated  iron  carbonate  by  the  mouth,  in  doses  of 
one  hundred  milligrammes  a  day,  or  the  rubbing  into  the  skin  of  the  same  prepa- 
rations, does  not  perceptibly  alter  the  elimination  of  iron  ;  so  that  positive  proof  is 
still  wanting  that  this  and  similar  preparations  of  the  Pharmacopoeia  are  taken  up 
by  the  human  organism,  although  Kunkel  reached  opposite  results  upon  animals. 
In  Busch's  experiments  it  was  found  that  either  pure  or  impure  haemoglobin,  given 
internally,  moderately  increased  the  elimination  of  iron  from  the  urine.  Peter 
Robert  Berry  *  in  a  micro-chemical  study  failed  to  detect  in  the  intestinal  walls  of 
the  animal  the  iron  whieh  had  been  exhibited  shortly  before. 

Notwithstanding  all  the  laboratory  evidence  just  summarized,  every 
clinician  knows  that  almost  any  one  of  the  ordinary  preparations  of  iron 
is  capable  of  increasing  the  amount  of  iron  in  the  blood  in  chlorosis,  and 
until  some  plausible  reason  other  than  that  which  is  natural — namely,  that 
the  iron  acts  after  absorption — is  given,  it  remains  highly  improbable 
that  iron  is  unabsorbed.  The  conclusion  that  the  human  body  is  capable 
of  absorbing  iron  from  the  Pharmacopoeial  preparations  has,  moreover, 
recently  received  so  much  of  experimental  corroboration  that  it  would 
appear  to  be  an  established  truth. 

In  the  first  place,  Socin  *  has  shown  that  it  is  scarcely  possible  to  determine  the 
question  of  iron  absorption  by  the  simple  comparison  of  the  iron  ingested  and 
eliminated.  In  the  second  place,  the  chemists  upon  whose  work  so  much  has  been 
presaged  studied  the  renal  elimination  of  iron  only ;  whereas  the  metal  escapes 
even  more  freely  through  the  intestinal  tract  than  through  the  kidneys.  Thus,  Gott- 
lieb, feeding  dogs  on  food  practically  free  from  iron,  was  able  to  obtain  from  the 


TONICS.  445 

faeces  nearly  ninety-seven  per  cent,  of  iron  which  had  been  subcutaneously  injected. 
He  also  demonstrated  that  twenty  to  sixty-five  per  cent,  of  the  injected  iron  could 
at  a  certain  time  be  found  in  the  liver.  Carl  Jacob! 5  found  that  after  the  intra- 
venous injection  of  iron,  renal  elimination  ceased  in  the  dog  in  from  two  to  three 
hours,  after  which  fifty  per  cent,  of  the  injected  iron  could  be  recovered  from  the 
liver.  Zaleski 6  affirms  that  iron  is  especially  eliminated  by  the  liver. 

In  the  third  place,  there  is  direct  proof  of  absorption.  Kunkel 7  for  eight  weeks 
fed  two  dogs  upon  milk,  giving  to  one  of  them  iron  in  addition,  and  bleeding  each 
dog  equally  from  time  to  time.  After  the  killing  of  the  dogs  the  blood  and  the 
various  organs  of  the  body  were  carefully  analyzed,  and  it  was  found  that  iron  was 
in  distinct  excess  in  all  the  organs  of  the  dog  to  which  the  metal  had  been  given,  and 
that  in  the  blood  there  was  one  and  a  half  times  as  much  of  the  iron,  and  in  the  liver 
eight  times  as  much,  as  in  the  similar  tissues  or  organs  of  the  dog  used  for  control. 
Justus  Gaule  8  detected  chemically  iron  in  the  lymph  coming  from  the  thoracic  duct 
of  a  rabbit  into  whose  stomach  a  dilute  solution  of  the  ferric  chloride  had  been  in- 
jected. Quincke  9  not  only  proved  that  iron  is  excreted  from  the  mucous  mem- 
brane of  the  large  intestine,  but  also  that  absorbed  iron  can  be  detected  in  the 
walls  of  the  duodenum,  a  fact  which  has  been  confirmed  by  Hall,10  by  A.  Hoff- 
mann,11 and  by  Hare.12  Hall  further  discovered  that  if  the  feeding  of  a  carnivo- 
rous animal  with  iron  had  been  long  continued,  the  metal  could  be  detected  in 
the  pulp-cells  of  the  spleen  and  in  the  hepatic  acini  around  the  central  vein.  The 
conclusion  of  Hall,  that  iron  occurs  in  the  human  system  in  two  forms,  one  a 
fixed  organic  combination, — haemoglobin, — the  other  an  inorganic  or  a  very  loose 
organic  combination,  is  very  plausible.  According  to  Hall,  it  is  the  second  combi- 
nation whose  amount  in  the  system  continually  varies  with  that  of  the  iron  taken 
into  the  alimentary  canal. 

Spurred  on  by  the  theory  that  the  inorganic  preparations  of  iron  are 
not  absorbed,  pharmaceutical  chemists  have  put  forth  many  organic  prep- 
arations. Of  these,  dried  blood  or  an  impure  hemoglobin  was  naturally  the 
first  to  be  exploited.  Bunge  suggested  a  ferruginous  nucleo-albumin 
obtained  from  egg-yolk,  to  which  he  gave  the  name  of  hcematogen  ;  whilst 
Schmiedeberg  and  Marfori,13  under  the  name  of  ferratin,  commended  a 
proteid  compound  containing  from  four  to  eight  per  cent,  of  iron,  which 
is  affirmed  to  be  the  form  in  which  iron  exists  in  the  liver,  and  out  of 
which  in  the  body  the  haemoglobin  is  directly  made.  There  is,  however, 
neither  clinical  nor  experimental  evidence  indicating  that  ferratin  is  supe- 
rior to  the  older  compounds.  Hochhaus  and  Quincke  u  found  that  ferra- 
tin and  the  older  compounds  could  be  traced  through  the  duodenum  into 
the  mesenteric  glands  with  equal  facility  ;  and  in  an  elaborate  study  on 
the  absorption  and  elimination  of  the  iron,  Cloetta 15  was  unable  to  per- 
ceive any  difference  between  organic  and  inorganic  preparations  of  iron 
in  relation  to  their  building  up  of  the  blood. 

When,  in  anaemia,  there  is  need  of  more  supply  of  material  for  the 
manufacture  of  blood-corpuscles,  the  immediate  usefulness  of  iron  is  very 
explicable  ;  but  in  most  cases  of  serious  anaemia,  even  when  that  anaemia 
is  of  the  chlorotic  type  and  is  relieved  by  the  use  of  iron,  there  has  been 
no  lack  of  ferruginous  food  ;  so  that  it  is  probable  (not  proven)  that 
medicinal  iron  has  a  direct  stimulant  influence  upon  those  organs  which 
produce  the  red  blood-corpuscles. 


446  GENERAL  REMEDIES. 

Miiller "  has  found  that  in  dogs  rendered  anaemic  by  repeated  bleeding  and  a 
diet  as  free  as  possible  from  iron  that  the  administration  of  an  inorganic  salt  of  iron 
increased  the  number  of  nucleated  corpuscles  in  the  blood.  It  would  seem,  there- 
fore, that  iron  has  a  direct  stimulant  influence  upon  the  formation  of  red  blood-cells 
in  the  bone  marrow. 

The  question  whether  or  not  iron  acts  as  a  stimulant  to  the  blood- 
making  organs  is  closely  connected  with  the  question  as  to  the  effect  of 
iron  upon  healthy  individuals.  It  was  formerly  believed  that  the  proper 
administration  of  the  metal  to  healthy  man  would  produce  an  excess  of 
the  red  blood-corpuscles,  but  more  recent  investigations,  whilst  somewhat 
discordant  and  not  conclusive,  have  unsettled  this  belief. 

The  experiments  of  Nasse  lf  upon  dogs  are  in  favor  of  the  older  view,  while, 
those  of  E.  C.  Cutler  and  E.  H.  Bradford  are  in  opposition  to  it.*  The  first  ob- 
server, giving  iron  with  fat,  noted  not  only  an  increase  of  bodily  weight,  but  also 
that  the  specific  gravity  of  the  blood  rose  from  1052  to  1060.8,  and  the  amount  of 
the  metal  in  the  blood  from  0.477  to  0.755  Per  thousand  parts,  both  the  result  of 
increase  in  the  corpuscular  element.  Cutler  and  Bradford  experimented  upon  man, 
using  the  tubes  of  M.  Malassez,  the  result  being  slight  diminution  of  the  red  blood- 
disks.  As,  however,  the  experiments  were  only  two  in  number,  and  the  subjects 
not  under  complete  control  as  to  conditions  of  life,  these  observations  can  hardly 
be  considered  conclusive. 

It  appears  to  be  a  well-established  fact  that  one  of  the  functions  of  the  red 
blood-corpuscles  is  to  convert  oxygen  into  ozone,  which  is  the  efficient  form  of  the 
element  in  the  system  (see  A.  Sasse17).  The  iron  oxide  outside  of  the  body  cer- 
tainly possesses  an  ozonizing  power  similar  to  that  of  the  red  disk.  Thus,  a  spot 
of  iron  mould — i.e.,  iron  oxide — on  linen  will  in  time  destroy  the  fabric.  The  reason 
of  this  is  the  corroding  action  of  the  ozone  which  is  slowly  generated  by  the  iron 
oxide.  From  a  similar  cause  a  fleck  of  rust  on  a  bright  surface  of  steel  will  steadily 
enlarge  and  deepen.  It  would  seem  a  priori  probable  that  in  the  blood  iron  acts 
as  it  does  out  of  the  body.  If  this  be  so,  by  increasing  oxidation  an  increase  of  the 
iron  in  the  blood  should  cause  elevation  of  temperature  and  increased  elimination 
of  urea.  The  studies  of  W.  Pokrowsky18  have  shown  that,  in  cases  of  anaemia, 
after  the  exhibition  of  iron  the  temperature  does  rise,  even  when  in  the  beginning  it 
was  not  below  normal,  and  that  simultaneously  there  is  an  increase  in  the  daily 
elimination  of  urea  ;  and  the  experiments  of  Botkin,  as  quoted  by  Sasse  (we  have 
not  seen  the  original),  establish  the  same  fact  in  regard  to  healthy  men.  The  in- 
creased oxidation  cannot  be  due  simply  to  an  increase  in  the  number  of  the  red 
corpuscles,  for  while  the  latter  accrue  slowly,  Pokrowsky  found  that  the  tempera- 
ture sometimes  rose  within  five  hours  after  the  exhibition  of  the  first  dose. 

From  the  evidence  just  educed  it  would  seem  that  iron  increases  the 
ozonizing  power  of  the  blood. 

THERAPEUTICS. — Leaving  out  of  consideration  those  cases  which  may 
be  spoken  of  as  instances  of  "accidental  anaemia," — i.e.,  anaemia  due  to 
hemorrhage,  poison,  starvation,  or  other  temporary  cause,  which  has 

*  V.  H.  Meyers  and  F.  Williams  (Arch.  f.  Exper.  Path.  u.  Pharm.,  xiii.  76)  have 
studied  the  effects  of  enormous  doses  of  the  iron  and  sodium  tartrate  upon  the  lower 
animals.  Both  frogs  and  mammals  are  killed  by  it,  the  symptoms  in  warm-blooded  ani- 
mals being  vomiting,  purging,  great  fall  of  the  blood-pressure,  muscular  weakness,  and 
finally  coma  and  death.  The  experiments  show  that  the  heart  is  not  much  affected,  but 
the  vaso-motor  system  and  the  spinal  motor  centres  are  paralyzed. 


TONICS.  t  447 

passed  off  or  is  removable,  and  in  which  iron  may  be  given  as  an  aid  to 
the  rebuilding  of  the  blood, — we  find  that  practically  the  anaemias  are 
divided  into  two  sets  :  those  in  which  there  is  a  pronounced  lessening 
in  the  percentage  of  haemoglobin  in  the  blood  but  not  a  corresponding 
lessening  in  the  number  of  red  blood-corpuscles,  and  those  in  which  the 
red  blood -corpuscles  are  greatly  diminished  in  number.  The  first  class 
of  cases  is  typified  in  chlorosis,  the  second  in  the  essential  anaemias. 

Of  the  value  of  iron  in  chlorosis  there  can  be  no  doubt.  Thus,  Simon 19 
reports  a  case  of  chlorosis  in  which,  under  the  steady  use  of  iron  for 
sixty-four  days,  the  globulin  increased  from  30.86  parts  to  90.80  parts  per 
thousand,  and  the  haemoglobin  from  1.431  parts  to  4.598  parts  per  thou- 
sand ;  and  Cutler  and  Bradford  'J0  have  obtained  confirmatory  results  with 
Malassez's  tubes.  In  most  cases  of  essential  anamia  with  great  lessening 
in  the  number  of  red  blood-corpuscles,  typified  by  leukamia  and  per- 
nicious  an&mia,  iron  is  of  no  service  whatever.  Unfortunately,  the  line 
between  the  two  sets  of  cases  of  anaemia  is  in  nature  not  so  sharp  as  it 
can  be  made  in  treatises,  and  we  have  seen  cases  presenting  a  chlorotic 
form  of  anaemia,  in  which  the  anaemia  failed  to  be  affected  at  all  by  iron 
or  any  other  treatment,  remaining  almost  as  persistent  and  unconquer- 
able as  the  blood-lesion  of  leucocythaemia. 

Almost  all  the  preparations  of  iron  are  more  or  less  astringent,  and 
when  in  the  blood  very  probably  exert  a  direct  influence  upon  the  tissues, 
contracting  them  not  merely  by  increasing  their  tone,  but  also  by  acting 
on  their  vital  contractility. 

The  preparations  of  iron  may  be  divided  into  those  which  are  soluble 
and  those  which  are  insoluble  in  water.  At  first  sight  it  would  appear 
that  the  former  class  of  preparations  would  be  those  most  readily  ab- 
sorbed. The  experiments  of  Quevenne  have,  however,  demonstrated 
that  solubility  is,  so  far  as  iron  is  concerned,  no  evidence  of  absorbability. 
Quevenne  asserts  that  the  reduced  iron  yields  the  largest  percentage 
to  the  gastric  juice,  and,  as  it  is  nearly  free  from  astringency,  it  is  one  of 
the  best  of  the  chalybeates  for  use  in  pill  form  :  but  little,  if  any,  inferior 
is  the  saccharated  carbonate.  If  a  soluble  preparation  be  desired,  the 
ammonic  or  potassic  tartrates  are  very  unirritating.  When  freely  given, 
almost  all  preparations  of  iron  form  in  the  intestines  sulphides,  which 
blacken  the  faeces. 

There  are  persons  in  whom  iron  produces  headache  :  this  can  in 
some  cases  be  obviated  by  the  use  of  laxatives.  The  observations  of 
M.  Petit,  N.  A.  Bubnow,21  etc.,  that  the  iron  preparations  in  large  doses 
inhibit  the  digestive  processes,  throw  some  light  upon  these  cases.  Our 
experience  is  that  gouty  or  rheumatic  patients  bear  iron  badly,  and 
that  sometimes  its  exhibition  seems  to  aggravate  the  arthritic  symptoms. 
The  chief  centra-indications  for  the  use  of  iron  is  the  existence  of  plethora 
or  of  catarrhal  disease  of  the  gastro-intestinal  tract. 

The  peculiar  actions  of  certain  salts  of  iron  will  be  considered  under 
their  respective  preparations. 


448  GENERAL    REMEDIES. 

FERRUM  REDUCTUM.  U.  S. — REDUCED  IRON. — FERRI  PULVIS,  Iron 
by  Hydrogen,  Quevenne1  s  Iron. 

This  substance  is  made  by  exposing  ferric  oxyhydrate  at  a  white  heat  to  the 
action  of  hydrogen,  which  takes  away  the  oxygen  and  leaves  metallic  iron.  It 
occurs  as  a  light,  iron-gray,  tasteless  powder,  which  should  be  completely  dissolved 
by  dilute  sulphuric  acid  without  yielding  the  odor  of  sulphuretted  hydrogen,  and 
when  touched  with  a  lighted  taper  should  ignite  and  burn  to  the  brown  iron  oxide. 
If  it  be  black,  or  if  it  fail  to  answer  the  tests  given  above,  it  is  impure  ;  and  indeed, 
as  offered  in  the  shops,  not  rarely  it  is  entirely  spurious. 

Reduced  iron  is  an  efficient  chalybeate,  very  free  from  astringency. 
Dose,  two  to  five  grains  (0.13-0.3  Gm. ),  in  pill,  capsule,  or  chocolate 
lozenge. 

FERRI  HYDROXIDUM.  U.  S. — FERRIC  HYDRATE. — The  Hydrated 
Oxide  of  Iron,  made  by  precipitating  ferric  sulphate  with  ammonia,  is  a 
reddish-brown  powder,  which  is  used  solely  as  an  antidote  to  arsenic. 

For  antidotal  purposes  ferric  hydrate  should  be  freshly  prepared,  and  should  be 
so  moist  as  to  constitute  a  magma.  Its  virtues  are  deteriorated  by  age,  even  when 
it  is  kept  under  water,  and  are  entirely  destroyed  by  drying.  If  the  solution  of  the 
ferric  sulphate  be  not  at  hand  in  an  emergency,  the  chloride  will  yield  just  as  useful 
a  product,  and  sodium  carbonate  or,  better  still,  magnesium  carbonate,  may  be 
substituted,  if  circumstances  necessitate  it,  for  the  ammonia.  The  precipitate  falls 
at  once,  and  may  be  washed  by  putting  it  in  a  piece  of  muslin,  squeezing  out  the 
original  fluid,  and  then  pouring  on  some  fresh  water. 

As  the  ferric  hydrate  is  perfectly  innocuous,  it  should  be  very  freely 
administered  when  used  as  an  antidote,  especially  since  it  acts  only  when 
in  excess.  A  tablespoonful  may  be  stirred  up  in  water  and  taken  at  once, 
the  dose  being  repeated  several  times  if  necessary.  The  FERRI  HYDROXI- 
DUM CUM  MAGNESII  OXIDO,  U.  S. ,  differs  from  the  ferric  hydrate  in  con- 
taining magnesia,  which  is  substituted  in  excess  for  the  ammonia  as  a 
precipitant.  As  magnesia  is  not  at  all  irritant,  and  is  itself  antidotal  to 
arsenic,  the  latter  preparation  offers  decided  advantages  over  the  older 
antidote.  It  should  be  given  freely. 

FERRI  CARBONAS  SACCHARATUS — SACCHARATED  FERROUS  CAR- 
BONATE. U.  S. 

This  greenish-gray  powder  is  made  by  precipitating  a  solution  of  the  ferrous 
sulphate  by  sodium  bicarbonate  and  adding  sugar  in  sufficient  quantities.  During 
drying,  sugar  is  kept  constantly  present  in  large  amount,  so  as  to  prevent  the 
absorption  of  oxygen,  and  the  consequent  conversion  of  the  ferrous  carbonate  into 
the  ferric  oxide. 

This  carbonate  is  a  very  good  chalybeate,  nearly  free  from  astringency. 
Dose,  three  to  five  grains  (0.2-0.3  Gm. ),  in  pill.  Griffith' s  Mixture 
(MiSTURA. FERRI  COMPOSITA,  U.  S.)  contains  the  ferrous  carbonate  and 


TONICS.  449 

myrrh,  and  has  been  much  used  in  an&mia  with  amenorrhcea  in  doses 
of  from  one  to  two  tablespoonfuls  (15-30  C.c. ). 

FERRI  SULPHAS — FERROUS  SULPHATE.  U.  S. — Ferrous  sulphate 
occurs  in  transparent,  efflorescent,  rhombic  prisms  of  a  pale  bluish-green 
color  and  a  metallic  styptic  taste.  It  is  also  official  in  a  granular  form 
(FERRI  SULPHAS  GRANULATUS).  It  is  a  very  decided  astringent,  and 
in  a  concentrated  form  and  sufficient  amount  acts  as  an  irritant  poison, 
producing  vomiting,  purging,  and  gastro-intestinal  inflammation.*  Ex- 
ternally its  solution  (five  to  twenty-five  grains  to  the  fluidounce)  has  been 
used  as  an  astringent  lotion,  especially  in  erysipelas.  As  a  simple  cha- 
lybeate the  ferrous  sulphate  should  never  be  used.  In  chronic  diarrhoea 
it  is  sometimes  employed  as  a  tonic  astringent.  Dose,  one  to  two  grains 
(0.06-0.12  Gm. )  ;  in  the  form  of  the  dried  sulphate  (FERRI  SULPHAS 
EXSICCATUS,  U.  S. ),  one-half  to  one  grain  (0.03-0.06  Gm. ). 

LIQUOR  FERRI  SUBSULPHATIS — SOLUTION  OF  FERRIC  SUBSUL- 
PHATE.  U.S. — MONSEL'S  SOLUTION. — The  solution  of  the  subsulphate 
(of  the  sesquioxide)  of  iron  (often  incorrectly  called  solution  of  the  per- 
sulphate of  iron)  is  a  very  active  astringent  and  blood-coagulant  :  being 
also  only  slightly  irritant,  it  is  perhaps  the  most  efficient  of  the  styptics, 
but  must  in  hemorrhage,  to  be  efficient,  be  applied  directly  to  the  part. 
In  h&matemesis  five  minims  (0.3  C.c.)  of  it  may  be  given  in  from  one 
to  two  ounces  of  water,  repeated  if  necessary.  The  atomization  of  its 
watery  solution  (from  five  to  twenty  drops  to  the  ounce)  often  acts  well 
in  hemoptysis.  The  pulverization  of  the  liquid  should  be  complete,  and 
the  inhalation,  which  should  last  for  five  to  twenty  minutes,  may  be 
repeated  at  intervals  of  an  hour  or  longer.  In  diphtheria  Monsel's  solu- 
tion is  very  valuable  applied  freely,  of  full  strength  or  diluted  pro  re  nata, 
to  the  throat  every  three  to  twelve  hours.  In  overdose  Monsel's  solu- 
tion is  an  irritant  poison  ;  the  antidote  is  soap  or  an  alkaline  carbonate. 

The  Solution  of  Ferric  Sulphate  (  LIQUOR  FERRI  TERSULPHATIS, 
U.  S. ),  owing  to  its  irritant  action,  is  used  only  to  make  the  ferric  prepa- 
rations. 

TINCTURA  FERRI  CHLORIDI.  U.  S.—  Tincture  of  Ferric  Chloride. 
— This  preparation  contains  the  ferric  chloride,  hydrochloric  acid, 
and  alcohol,  and,  from  the  reactions  of  the  last  two  ingredients,  chloric 
ether.  It  is  a  reddish-yellow  liquid,  actively  chalybeate,  very  astrin- 
gent, and  possessed  of  peculiar  properties,  some  of  which  may  be  due 
to  the  ether  in  it.  Decidedly  diuretic  and  escaping  through  the  kid- 
neys, it  directly  affects  the  genito-urinary  mucous  membrane.  It  is 
much  used  in  chronic  Brighf  s  disease  and  combined  with  tincture  of 

*  In  a  case  reported  in  the  N.  Y.  Med.  Journ.,  xxxviii.  401,  the  early  symptoms,  as 
stated  by  the  patient,  were  chiefly  nervous  :  little  confidence  can,  however,  be  reposed  in 
the  patient's  report  of  symptoms  or  of  the  amount  ingested. 

29 


450  GENERAL    REMEDIES. 

cantharides  in  gleet.  In  erysipelas  it  is  constantly  employed  with  remark- 
able results,  controlling  the  disease  in  a  manner  not  yet  understood. 
Analogy  has  suggested  its  employment  in  other  adynamic  affections, 
such  as  diphtheria  and  pyaemia,  but  its  value  in  these  diseases  is  much 
more  doubtful.  It  is  so  destructive  to  the  teeth  that  except  in  the  tooth- 
less its  use  as  a  gargle  is  unjustifiable  ;  and  even  in  its  ordinary  thera- 
peutic use,  by  the  employment  of  a  tube,  etc. ,  the  teeth  should  be  pro- 
tected as  far  as  possible.  Dose,  ten  to  thirty  drops  (0.6-2  C.c. )  as  a 
chalybeate  three  times  a  day,  in  erysipelas  every  two  or  three  hours. 
The  orange-yellow,  crystalline,  deliquescent  Ferric  Chloride  (FERRI 
CHLORIDUM,  U.  S. )  is  rarely  used.  Liquor  Ferri  Chloridi,  U.  S. ,  Solu- 
tion of  Ferric  Chloride,  should  contain  twenty-nine  per  cent,  of  the  anhy- 
drous salt.  It  is  an  acid,  irritant,  reddish-brown  liquid,  of  which  the  dose 
is  two  minims  (0.15  C.c.). 

SYRUPUS  FERRI  IODIDI.  U.  S. — The  Syrup  of  Ferrous  Iodide  is  a 
transparent,  greenish  liquid,  of  a  sweet,  ferruginous  taste.  It  deposits 
no  sediment  on  keeping,  and  should  not  affect  the  color  of  starch.  If  it 
strikes  a  blue  color  with  the  latter  substance,  it  contains  free  iodine.  The 
syrup  of  ferrous  iodide  is  a  favorite  remedy  in  those  cases  of  anaemia  in 
which  there  is  a  distinct  scrofulous  taint.  It  is  believed  to  possess  the 
peculiar  alterative  powers  of  iodine,  conjoined  with  the  tonic  properties 
of  iron.  It  is  much  used  in  scrofulosis  occurring  in  anaemic  children  ; 
but  it  certainly  possesses  no  advantages  over  a  ferruginous  tonic  and 
iodine  when  given  separately  but  simultaneously.  Dose,  for  a  child  two 
years  old,  five  to  ten  drops  (0.3-0.6  C.c.)  ;  for  an  adult,  thirty  to  forty 
minims  (2-2.5  C.c.).  As  it  affects  the  teeth  very  seriously,  it  should 
always  be  freely  diluted  when  taken,  and  the  mouth  should  be  well 
washed  after  its  administration. 

FERRI  IODIDUM  SACCHARATUM.  U.  S.  1890 — Saccharated  Ferrous 
Iodide  is  a  yellowish-white  or  grayish  powder  which  represents  the  chem- 
ical and  medical  properties  of  the  corresponding  syrup,  being  prepared 
by  a  parallel  process.  It  may  be  substituted  for  the  syrup  in  doses  of 
from  two  to  five  grains  (0.13-0.3  Gm. ),  given  in  pill  form. 

FERRUM  DIALYSATUM. — Dialyzed  Iron  is  a  clear,  neutral,  nearly 
tasteless,  dark  red  liquid,  prepared  by  dialyzing  a  solution  of  the  chlo- 
ride of  iron.  Its  exact  chemical  composition  is  uncertain,  but  it  is  so- 
unstable  that  a  precipitate  is  at  once  produced  by  minute  quantities  of 
alkalies,  almost  all  soluble  salts,  and  many  organic  substances.  Owing  to- 
ils tastelessness  and  its  freedom  from  astringency  it  was  for  a  short  time 
much  used  as  a  chalybeate  in  doses  of  from  twenty  to  forty  drops  (1.2- 
2.5  C.c. ),  but  the  ferric  oxide  which  results  from  its  immediate  precipita- 
tion in  the  stomach  is  a  very  feeble  substance,  and  the  preparation  has 
almost  passed  out  of  vogue.  It  may,  however,  be  used  as  an  antidote 


TONICS.  45i 

to  arsenic.  Doses  of  a  tablespoonful  (15  C.c. )  may  be  given  every  five 
or  ten  minutes  pro  re  nata* 

There  are  five  official  Iron  Citrates,  each  soluble  in  water.  Two  of 
these  (FERRI  CITRAS  and  FERRI  ET  AMMONII  CITRAS)  occur  in  gar- 
nety  scales,  and  are  simply  mild  chalybeates.  Dose,  five  grains  (0.3 
Gm. ).  The  Iron  and  Quinine  Citrate  (FERRI  ET  QUININE  CITRAS), 
in  transparent  scales,  varying  from  reddish  brown  to  yellowish  brown  in 
color,  and  Soluble  Iron  and  Quinine  Citrate  (FERRI  ET  QUININE  CITRAS 
SOLUBILIS,  U.  S. ),  each  containing  twelve  per  cent,  of  alkaloid,  may  be 
given  in  doses  of  five  grains  (0.3  Gm. )  or  more.  The  Iron  and  Strych- 
nine Citrate  (  FERRI  ET  STRYCHNINE  CITRAS)  contains  one  per  cent,  of 
strychnine,  f  Dose,  two  grains  (o.  125  Gm. ).  FerriHypophosphis,  U.  S. , 
is  almost  insoluble.  Dose,  eight  grammes. 

There  are  two  official  Iron  Tartrates  (FERRI  ET  AMMONII  TARTRAS 
and  FERRI  ET  POTASSII  TARTRAS),  each  occurring  in  garnety  scales,  and 
each  soluble  in  water.  Dose,  five  grains  (0.3  Gm. ).  The  Ferrous  Lactate 
(formerly  official)  occurs  in  greenish-white  crystalline  crusts  or  grains, 
soluble  in  forty  parts  of  water.  It  is  a  good  chalybeate.  Dose,  five 
grains  (0.3  Gm. ).  Soluble  Ferric  Phosphate  (FERRI  PHOSPHAS 
SOLUBILIS)  and  Soluble  Ferric  Pyrophosphate  (FERRI  PYROPHOSPHAS 
SOLUBILIS)  are  excellent  preparations,  occurring  in  apple-green  scales, 
completely  soluble  in  water,  and  nearly  free  from  astringency  and  ferrugi- 
nous taste.  Dose,  five  grains  (0.3  Gm. ).  Ferric  Ammonium  Sulphate 
(FERRI  ET  AMMONII  SULPHAS,  U.  S. )  occurs  in  octahedral  crystals  of 
a  pale  violet  color  :  it  is  freely  soluble  in  water,  is  very  astringent,  and 
is  often  useful  in  atonic  leucorrhcea,  in  doses  of  five  grains,  three  times  a 
day. 

MANGANESE. — The  Manganese  Dioxide  (MANGANI  DIOXIDUM 
PRECIPITATUM  U.  S. ),  and  the  Manganese  Sulphate  (MANGANI  SULPHAS, 
U.  S. )  have  been  supposed  to  possess  therapeutic  properties  similar  to  those 
of  iron.  The  metal  manganese  certainly  exists  in  the  blood,  but  its  salts 
have  failed  to  gain  the  confidence  of  the  profession,  although  highly 
recommended  by  Harmon,  of  Belgium,  and  by  P6trequin  *  as  an  adju- 
vant to  the  chalybeates.  In  Garrod's2  experiments  upon  anaemia  the 
preparations  of  manganese  failed  to  be  of  service.  According  to  C.  C. 
Gmelin,  the  sulphate  acts  as  a  powerful  cholagogue  on  the  lower  animals, 
and  Thomson  states  that  it  is  a  purgative  to  man  in  doses  of  one  or  two 
drachms.  Leand  3  affirms  that  the  manganese  oxide  is  therapeutically 
equivalent  to  the  preparations  of  bismuth  excepting  in  that  it  does  not 
constipate,  and  that  it  may  be  used  with  advantage  in  gastralgia,  py- 
rosis, and  similar  stomachic  derangements.  Dose,  five  to  fifteen  grains 
(0.3-1  Gm.). 

*  See  Phila.  Med.  Times,  viii.  104,  151,  335. 

t  The  alkaloidal  compounds  with  iron  are  very  ineligible  preparations,  because  they 
do  not  allow  the  practitioner  to  vary  the  proportionate  doses  of  the  two  ingredients. 


452  GENERAL  REMEDIES. 

MINERAL  ACIDS. 

Sulphuric,  hydrochloric,  nitric,  and  nitro-hydrochloric  acids,  when  in 
concentrated  form,  rapidly  destroy  all  organic  tissues,  and  are,  therefore, 
corrosives,  hydrochloric  acid  being  the  feeblest. 

Owing  to  its  abstraction  of  the  element  of  water  from  the  carbon  of 
organic  tissues,  sulphuric  acid  blackens  organic  matter  at  the  same  time 
that  it  destroys  its  texture  ;  nitric  acid  stains  organic  tissue  a  deep  yellow 
color  ;  nitro-hydrochloric  acid  produces  a  somewhat  similar  but  much 
less  pronounced  discoloration.  In  the  detection  of  poisoning  by  one  of 
these  agents  the  color  of  the  stain  upon  the  person  or  clothing  is  often  of 
great  assistance.  Holes  made  in  the  linen  by  one  of  these  acids  are  to 
be  distinguished  from  those  made  by  fire  or  mechanical  violence  by  the 
pulpy  character  and  acid  reaction  of  the  edges. 

The  general  symptoms  of  poisoning  by  mineral  acids  are  similar,  and 
depend  for  their  severity  especially  upon  the  amount  and  the  concentra- 
tion of  the  dose  taken,  although  sulphuric  and  nitric  acids  are  more  power- 
ful than  is  hydrochloric  acid.*  Death  from  collapse  has  resulted  in  two 
and  a  half  hours,  but  months  may  be  required  in  the  working  out  of  the 
fatal  result.  The  symptoms  are  immediate  pain  in  the  mouth,  gullet, 
and  epigastrium,  violent  vomiting  (after  sulphuric  acid  the  matters  may 
be  tarry),  and  rapid  collapse  marked  by  cold  wet  surface,  feeble  pulse, 
and  suppressed  voice.  The  mind  is  usually  clear  until  very  late  in  the 
poisoning. 

After  a  small  dose  the  chief  symptoms  may  be  connected  with  the 
upper  digestive  passages.  Thus,  Maukopff  has  recorded  suppurative 
parotitis  largely  due  to  the  closure  of  the  duct  of  Steno.  Ulceration 
of  the  larynx  or  oesophagus  has  frequently  been  noted.  Desquamative 
nephritis  may  be  developed  several  days  after  subsidence  of  the  first 
symptoms.  In  a  case  of  sulphuric  acid  poisoning  recorded  by  Maukopff, 
the  urine  which  had  ceased  to  be  albuminous  on  the  third  day  became  so 
again  on  the  twentieth,  with  a  simultaneous  development  of  casts  contain- 
ing blood-corpuscles  ;  after  death  tubular  nephritis  was  found.  Another 
symptom  noted  by  Maukopff  was  intercostal  neuralgia. 

After  death,  destruction  of  the  oesophagus,  stomach,  or  air-passages 
is  usually  found,  the  color  of  the  slough — black  after  sulphuric,  yellow 
after  nitric  acid — being  characteristic.  Probably  in  all  cases  in  which 
death  does  not  take  place  too  early,  wide-spread  degeneration  of  proto- 
plasm takes  place.  A.  D.  Kazowsky,1  has  found  that  this  involves  the 
cells  of  the  heart-ganglia,  which  undergo  parenchymatous  swelling,  fol- 
lowed by  necrosis  of  the  cells  and  vacuolization  not  only  of  the  nuclei 
but  also  of  the  general  protoplasm. 

When  the  dose  has  not  been  sufficient  to  kill,  protracted  illness  from 
local  organic  alterations  usually  results. 

*  Cases  of  sulphuric  acid  poisoning  (Med.  Times  and  Gaz.,  1863,  i.). 


TONICS.  453 

The  treatment  of  a  case  of  acid-poisoning  consists  in  the  immediate 
administration  of  soap,  chalk,  whitewash,  magnesia,  or  other  available 
antidote.  Notwithstanding  Christison's  condemnation  of  the  alkaline 
carbonates  as  too  irritating,  they  should  be  used  unhesitatingly  in  dilute 
form  if  immediately  at  hand. 

ACIDUM  SULPHURICUM.     U.  S. — SULPHURIC  ACID. — Oil  of  Vitriol 

| 

is,  when  pure,  a  colorless,  heavy  liquid  which  on  exposure  to  the  air 
rapidly  absorbs  moisture.  The  official  acid  has  a  sp.  gr.  1.826. 

Concentrated  sulphuric  acid  is  not  rarely  used  as  an  escharotic,  for 
which  purpose  it  is  mixed  with  finely  powdered  charcoal  so  as  to  form  a 
paste.  Appropriately  diluted,  it  has  been  employed  as  a  stimulant  and 
astringent  lotion  in  venereal  and  other  indolent  ulcers.  Internally,  sul- 
phuric acid  is  very  useful  as  an  astringent  in  colliquative  sweats  (night- 
sweats}  and  in  profuse  serous  diarrhoeas.  We  have  used  it  with  great 
advantage  in  the  sudden  serous  vomiting  and  purging  of  infants  known 
as  cholera  infantum. 

It  has  been  employed  with  advantage  in  cholera,  and  a  remarkable 
series  of  observations  by  R.  G.  Curtin  *  at  least  furnish  good  reason  for 
further  testing  its  powers  as  a  prophylactic  against  this  disease. 

The  facts  recorded  by  Curtin  are  as  follows.  A  very  severe  epidemic  of  the 
disease  ceased  in  the  Insane  Department  of  the  Philadelphia  Almshouse  within 
twelve  hours  after  the  lunatics  were  all  put  upon  the  free  use  of  sulphuric  acid  lem- 
onade, the  only  new  case  after  this  being  in  a  man  who  refused  to  use  the  prophy- 
lactic. Two  days  after  the  use  of  the  sulphuric  acid  was  stopped  two  new  cases 
occurred,  and  the  epidemic  was  again  arrested  by  the  use  of  the  acid.  In  the  sur- 
gical wards  of  the  Hospital  Department  the  acid  was  used  from  the  beginning  of 
the  epidemic ;  and  these  wards,  although  in  no  way  isolated,  were  the  only  parts 
of  the  institution  unvisited  by  the  disease.  The  sulphuric  acid  probably  acted  by 
producing  an  excessive  acidity  of  the  alimentary  canal,  it  being  well  assured  that 
the  cholera  organism  will  develop  only  in  an  alkaline  condition  of  the  alimentary 
tract.  Thus,  the  dog,  whose  digestive  tract  is  highly  acid,  resists  the  action  of  the 
bacillus  unless  an  alkaline  carbonate  be  freely  given,  when  choleraic  symptoms 
appear  after  the  administration  of  the  cholera  organism. 

Sulphuric  acid  was  formerly  used  in  hemorrhages,  but  is  now  rarely 
employed.  It  is,  we  think,  much  less  efficacious  than  are  some  other  reme- 
dies. In  acute  lead-poisoning  the  dilute  acid  is  an  efficient  antidote,  and 
in  white  lead  works  the  free  use  of  sulphuric  acid  lemonade  by  the  em- 
ployees is  said  to  be  advantageous  as  a  prophylactic  against  the  chronic 
poisoning. 

ADMINISTRATION. — Sulphuric  acid  should  be  given  properly  diluted, 
and  with  the  requisite  precautions  to  prevent  its  injuring  the  teeth.  It  is 

*  It  is  very  probable  that  other  acids  are  equally  antidotal  to  the  cholera  germ,  since 
Richard  P.  Strong  found  that  the  addition  of  one  per  cent,  of  citric  acid  to  water  infected 
with  the  cholera  germ  made  it  safe  to  drink.  It  was  noted  further  that  a  large  Philippine 
lemon,  containing  forty  cubic  centimetres  of  juice,  was  equivalent  to  2.74  grammes  of 
citric  acid. — Report  Government  Laboratories,  Philippine  Islands,  Sept.  i,  1903. 


454  GENERAL  REMEDIES. 

best  administered  in  the  form  either  of  the  dilute  (AciDUM  SULPHURI- 
CUM  DILUTUM — ten  per  cent,  by  weight,  U.  S.  ;  sp.  gr.  1.070  ;  dose, 
fifteen  to  thirty  drops  (1-2  C.c. )  or  of  the  aromatic  sulphuric  acid 
(AciDUM  SULPHURICUM  AROMATICUM — about  twenty  per  cent,  by 
weight,  U.  S. ).  The  last  preparation  contains  alcohol  and  aromatics.  Its 
dose  is  from  ten  to  twenty  drops  (0.6-1.3  C.c.),  well  diluted. 

ACIDUM  HYDROCHLORICUM.  U.  S. — Hydrochloric  Acid  is  a  color- 
less aqueous  solution  of  hydrochloric  acid  gas,  having  the  specific  gravity 
of  1.158  and  containing  31.9  per  cent,  by  weight  of  the  gas.  The  yel- 
lowish tint  of  commercial  hydrochloric  acid  is  due  to  the  presence  of 
ferric  chloride,  organic  matter,  or  other  substance. 

Hydrochloric  acid,  being  the  normal  digestive  acid  of  the  stomach, 
is  often  advantageous  in  cases  in  which  chronic  indigestion  is  connected 
with  the  failure  to  secrete  acid  in  the  stomach,  and  the  combination  of 
it  with  strychnine,  bitter  tonics,  and  aromatics  is  often  serviceable.  In 
the  so-called  "  Swedish  plan"  of  treatment  of  typhoid  fever,  hydrochloric 
or  other  mineral  acid  is  given  in  very  large  quantities.  Although  the 
method  was  at  one  time  much  in  vogue,  it  has  no  justification  in  results, 
and  is  to  be  avoided.  The  local  use  of  hydrochloric  acid  in  diphtheria, 
made  famous  by  Bretonneau,  has  deservedly  gone  into  oblivion.  As  a 
poison,  hydrochloric  acid  is  the  most  feeble  of  its  class,  recovery  having 
occurred  after  the  ingestion  of  an  ounce.* 

ADMINISTRATION. — The  acid  is  best  given  in  the  form  of  the  official 
ACIDUM  HYDROCHLORICUM  DILUTUM  (ten  per  cent.;  sp.  gr.  1.049). 
Dose,  ten  to  thirty  drops  (0.6-2  C.c.),  properly  diluted. 

ACIDUM  NITRICUM.  U.  S. — Nitric  Acid  is  a  liquid  of  the  specific 
gravity  of  about  1.403,  which  as  first  made  is  colorless,  but  by  exposure 
to  the  light  acquires  a  yellow  tint.  It  oxidizes  all  the  common  metals 
except  gold,  and  is  exceedingly  corrosive  to  living  tissue,  which  it  stains 
an  indelible  yellow.  When  diluted  it  converts  most  animal  and  vegeta- 
ble substances  into  oxalic,  malic,  or  carbonic  acid. 

When  taken  internally  in  small  amount,  nitric  acid  acts  as  a  stimulant 
upon  the  glandular  system  of  the  alimentary  canal,  and  in  serous  diar- 
rhoea appears  to  exert  an  astringent  influence. 

Nitric  acid  is  frequently  used  as  a  powerful  escharotic  in  cases  of 
chancre,  venereal  or  other  warts,  hospital  and  other  acute  gangrenes.  In 
many  instances  in  which  formerly  it  was  relied  upon  it  has  been  replaced 
by  antiseptic  measures. 

In  its  employment  care  should  be  taken  to  protect  the  sound  tissue  by  oil  or, 
still  better,  by  a  layer  of  soap.  It  may  be  applied  by  means  of  a  splinter  of  wood, 
or,  if  it  is  to  be  used  more  freely,  by  a  little  mop.  When  it  has  penetrated  as  deeply 
as  is  desirable,  washing  the  part  with  warm  soapsuds  will  prevent  further  action. 

*  See  Boston  Medical  and  Surgical  Journal,  xv. 


TONICS.  455 

Internally,  nitric  acid  has  been  used  in  low  fevers,  but  with  very  doubt- 
ful advantage.  In  dyspepsia,  in  chronic  hepatic  congestion,  in  the  oxalic 
acid  diathesis,  and  in  the  dyscrasia  of  constitutional  syphilis  nitric  acid 
has  been  employed  with  advantage,  but  is  much  inferior  to  nitro-hydro- 
chloric  acid. 

In  1826  Hope  asserted  that  ACIDUM  NITROSUM  has  a  specific  action  in 
serous  diarrhoea,  including  the  sudden  acute  diarrhoeas  of  hot  climates, 
and  in  the  chronic  dysenteries  originating  under  similar  circumstances. 
The  formula  he  employed  is  as  follows  :  R  Acidi  nitrosi,  fsji  ;  Misturae 
camphorae,  f^viii  ;  Misce,  et  adde  Tinct.  opii,  gtt.  xl.  S. — A  fourth  part 
to  be  taken  every  three  or  four  hours. 

Under  the  name  of  Hope's  Camphor  Mixture  a  preparation  similar  to  this  has 
been  much  used,  but  nas  gradually  lost  the  confidence  of  the  profession,  chiefly,  we 
believe,  because  on  theoretical  grounds  the  original  formula  has  been  departed 
from.  The  Nitrous  Acid  oi  the  shops  (  ACIDUM  NITROSUM,  Edinburgh  Pharmaco- 
poeia) is  an  orange-red  liquid,  which  may  be  looked  upon  as  a  solution  of  nitric 
oxide  in  nitric  acid.  When  it  is  diluted  with  water  it  is  after  a  short  time  converted 
into  simple  nitric  acid.  For  this  reason  it  has  been  customary  to  substitute  nitric 
acid  for  the  Acidum  Nitrosum  of  Hope's  original  formula.  It  should  be  noted, 
however,  that  the  latter  provided  only  sufficient  of  the  remedy  to  last  a  few  hours, 
and,  as  the  reaction  which  has  been  spoken  of  requires  some  time  for  its  perform- 
ance, we  do  not  think  that  theory  in  truth  warrants  the  change.  Practically  we 
have  failed  with  the  new  formula,  when  immediate  relief  was  afterwards  obtained 
by  the  use  of  the  medicine  prepared  according  to  the  old  plan.  Made  in  this  way 
and  used  while  fresh,  Hope's  Camphor  Mixture  is  a  very  efficient  though  disagree- 
able remedy  in  serous  diarrhoeas  connected  with  disordered  secretion  of  the  liver 
and  other  glands  of  the  alimentary  canal. 

ADMINISTRATION. — Dose,  from  five  to  twenty  drops  (0.3-1.2  C.c. ); 
of  the  ACIDUM  NITRICUM  DILUTUM,  U.  S.  (ten  per  cent.  ;  sp.  gr.  1.054), 
from  fifteen  to  sixty  drops  (1-4  C.c.). 

ACIDUM  NITRO-HYDROCHLORICUM.  U.  S. — Nitro- Hydrochloric  Acid 
is  made  by  mixing  nine  parts  of  nitric  acid  with  forty-one  parts  of  hydro- 
chloric acid.  If  the  acid  be  sufficiently  strong,  an  orange-colored  liquid 
will  be  formed  with  the  evolution  of  intensely  irritating  vapors. 

After  standing  for  a  length  of  time,  the  red  color  of  freshly  mixed  nitro-hydro- 
chloric  acid  changes  to  a  golden  yellow.  It  is  in  this  state  that  the  U.  S.  Pharma- 
copoeia directs  the  acid  to  be  used.  By  longer  standing  the  golden  yellow  becomes 
lemon  yellow,  and  the  odor  of  chlorine  is  almost  entirely  lost.  These  changes  are 
hastened  by  light,  but  will  occur  in  the  dark  and  in  well-stopped  bottles.  Although 
the  golden-yellow  acid  is  directed  by  the  Pharmacopoeia,  yet  careful  clinical  studies 
have  convinced  us  that  the  acid  acts  much  more  efficiently  when  freshly  prepared 
and  of  a  deep  red  color.  In  some  cases  it  has  seemed  to  us  useful  only  when  in 
the  latter  form.  The  lemon-yellow  acid  is  comparatively  inactive. 

The  remedial  value  of  nitro-hydrochloric  acid  depends  chiefly  upon 
the  power  which  it  possesses  to  a  much  greater  degree  than  any  other 
of  the  mineral  acids  of  influencing  the  action  of  the  liver  and  other 


456  GENERAL   REMEDIES. 

glandular  organs  of  the  alimentary  canal.  Originally  proposed  by  Scott, 
of  Bombay,  in  the  chronic  hepatitis  of  hot  climates,  it  has  been  used  with 
great  success  by  Annesley,  Martin,  and  other  famous  India  surgeons. 
The  remedy  would  seem  not  to  be  indicated  in  hepatitis  with  high  fever 
and  a  tendency  to  rapid  suppuration  so  much  as  in  the  slower  form  of  the 
affection,  which  normally  ends  in  chronic  enlargement  and  induration  of 
the  viscus.  Both  in  the  habitual  congestion  of  the  liver  and  in  the  milder 
affection  known  as  biliousness,  whose  pathology  is  probably  a  torpid  con- 
dition of  the  small  glands  of  the  alimentary  mucous  membrane  as  well  as 
of  the  liver,  nitro-hydrochloric  acid  has  yielded  in  our  hands  most  excellent 
results.  That  the  remedy  does  act  upon  the  liver  is  proved  by  the  fact 
that  in  these  cases  it  sometimes  produces  violent  bilious  diarrhoea.  When 
jaundice  depends  upon  obstruction  or  upon  any  of  the  severer  organic 
diseases  of  the  liver,  the  acid  is  of  little  if  any  use  ;  when,  however,  the 
jaundice  depends  upon  torpor  of  the  liver,  or  even  when  it  is  catarrhal  in 
origin,  the  remedy  may  be  of  great  service.  Even  in  the  early  stages  of 
cirrhosis,  while  the  liver  is  still  enlarged,  nitro-hydrochloric  acid  should 
be  tried,  as  in  some  cases  apparently  of  this  character  great  benefit  has 
been  derived  from  its  use. 

In  those  forms  of  chronic  diarrhcea  in  which  the  disease  is  really  an 
intestinal  dyspepsia,  nitro-hydrochloric  acid  may  be  of  great  service.  As 
the  effect  of  the  acid  is  not  a  sudden  one,  it  is  evident  that  it  acts  in 
these  cases  not  as  an  astringent,  but  by  restoring  the  normal  digestive 
power. 

There  is  a  morbid  condition,  oxaluria,  probably  dependent  upon  de- 
fective primary  assimilation,  in  which  the  chief  symptoms  are  general 
malaise,  a  feeling  of  weakness,  a  lack  of  elasticity,  and  a  very  great  de- 
pression of  spirits,  with  the  crystals  of  calcium  oxalate  generally  present 
in  the  urine,  and  in  which  nitro-hydrochloric  acid  produces  in  a  few  days 
a  surprising  revolution. 

As  a  "  blood-purifier' '  the  acid  has  been  employed  in  constitutional 
syphilis  and  in  various  ulcerative  skin  affections.  In  these  diseases  it  no 
doubt  does  good  by  improving  digestion  and  increasing  glandular  action, 
but  there  is  no  reason  to  believe  that  it  is  a  direct  alterative. 

ADMINISTRATION. — For  reasons  which  have  already  been  given,  when 
nitro-hydrochloric  acid  is  administered  internally  it  should  be  freshly  pre- 
pared ;  and,  as  the  changes  which  have  been  spoken  of  take  place  more 
rapidly  when  the  acid  is  mixed  with  water,  the  official  dilute  nitro-hydro- 
chloric acid,  twenty-two  per  cent. ,  is  an  ineligible  preparation.  As  light 
hastens  its  deterioration,  the  strong  acid  should  always  be  kept  in  a  dark 
bottle  with  a  glass  stopper.  Directly  after  mixing  the  acids  the  evolution 
of  gas  may  be  so  great  as  to  necessitate  its  being  allowed  to  escape.  After 
six  or  eight  hours,  however,  the  bottle  should  be  closely  stopped.  The 
dose  of  the  strong  acid  is  from  five  to  eight  drops  (0.3-0.5  C.c. ),  properly 
diluted,  and  taken  through  a  tube  after  meals. 

In  chronic  hepatic  diseases  the  external  application  of  the  acid  appears 


TONICS.  457 

to  give  even  better  results  than  its  internal  use.      In  India,  according  to 
Sir  Ranald  Martin,  the  bath  is  used  as  follows. 

Take  Hydrochloric  acid  f^iii,  Nitric  acid  f  .$ii,  Water  f  3v.  Mix.  Two  gallons 
of  water  and  six  fluidounces  of  the  above  mixture  suffice  for  a  bath,  which  will  keep 
fit  for  use  during  three  days,  provided  half  a  fluidounce  of  acid  and  a  pint  of  water 
are  added  morning  and  evening.  The  bath  must  of  course  be  given  in  wooden  or 
earthenware  vessels,  and  if  it  becomes  necessary  to  warm  it  only  a  portion  should 
be  heated  and  the  rest  then  added.  In  urgent  cases  the  whole  body  may  be  im- 
mersed in  the  bath  ;  but  generally  a  foot-bath  is  preferable,  the  inside  of  the  thighs 
and  arms  and  the  hepatic  region  being  at  the  same  time  sponged.  The  bath  should 
be  repeated  twice  daily,  lasting  each  time  for  ten  or  fifteen  minutes. 

We  have  had  no  experience  in  this  method  of  using  nitro-hydro- 
chloric  acid,  but  have  derived  great  benefit  from  the  application  of  the 
acid  over  the  hepatic  region. 

A  large  piece  (eight  by  ten  inches)  of  spongio-piline,  or  of  canton  flannel 
(several  layers),  should  be  wrung  out  in  a  lotion  of  a  strength  varying,  according  to 
the  irritability  of  the  patient's  skin,  from  one  to  three  fluidrachms  to  the  pint,  and 
applied  over  the  right  hypochondrium,  and  covered  with  a  piece  of  oiled  silk  sup- 
ported by  a  bandage.  The  application  sometimes  causes  a  prickling  sensation,  and 
after  a  time  may  produce  a  profuse  local  sweating.  The  dressing  may  be  left  on 
from  half  an  hour  to  an  hour,  and  be  repeated  three  or  four  times  a  day  :  some 
patients  can  wear  it  almost  continuously. 

LACTIC  ACID  (AciDUM  LACTICUM,  U.  S.,  seventy-five  per  cent,  of 
absolute  lactic  acid). — W.  Preyer,s  conceiving  that  sleep  is  due  to  the 
presence  in  the  blood  of  the  results  of  tissue-change,  among  which  is 
lactic  acid,  experimented  with  it  and  its  soda  salt,  and  announced  that 
they  acted  as  powerful  soporifics  upon  both  man  and  the  lower  animals. 
According  to  his  statements,  with  the  sleep  came  deep,  slow  respiration, 
and  lessening  of  reflex  activity  and  of  the  bodily  temperature.  It  has, 
however,  been  shown  *  that  the  hypnotic  powers  of  lactic  acid  and  its  salts 
are  very  feeble  and  uncertain.  The  large  doses  used  also  are  very  prone 
to  produce  irritation  of  the  alimentary  canal,  and  Senator  noticed  the  pro- 
duction of  rheumatic  pains.  From  three  to  nine  drachms  (12-36  Gm.) 
of  the  sodium  lactate  may  be  given  at  a  dose. 


REFERENCES. 

TRnKr  5-  JACOBI A.  E.  P.  P.,  xxviii.  3. 

6.  ZALESKI A.  E.  P.  P.,  xxiii. 

1.  HAMBURGER     .  .  Z.  P.  C.,  1879,  "•  7-  KUNKEL A.  G.  P.,  Ixi. 

2.  MOERNER  .   .   .  .  S.  Jb.,  ccxxxix.  227.  8.  GAULE D.  M.  W.,  1896,  xxii. 

3.  BERRY S.  Jb.,  ccxxxvi.  9.  QUINCKE    .   .   .   .  A.  E.  P.  P.,  1896,  xxxvii. 

4.  SOCIN Z.  P.  C.,  1890-91.  10.  HALL A.  A.  P.,  1896. 

*  E.  Mendel  (Deutsch.  Med.  Wochenschr.,  1876.  No.  17),  Erler  (Centralbl.  f.  Med. 
Wissens.,  1876,  658),  Fischer  (Land.  Med.  Record,  1877,  193),  Lothar  (  Virchow's  Archiv, 
Ixvi.  120),  and  Senator  (Berlin.  Klin.  Wochenschr.,  1877,  537). 


458 


GENERAL    REMEDIES. 


REFERENCES—  Continued. 


11.  HOFFMANN   .  .  .  V.  A.  P.  A.,  1895,  cli. 

12.  HARE Arch.    f.    Verdauungs 

Krank.,  1898. 

13.  SCHMIEDKBERG  and  MARFORI  .  A.    E.    P.    P., 

xxix.,  xxxiii. 

14.  HOCHHAU s  and  QUINCKE  .  A.   E.  P.  P.,  1896, 

xxxvii.  159. 

15.  CLOETTA    ....  A.  E.  P.  P.,  1897,  xxxviii. 

161. 

16.  NASSE L.  M.  R.,  1877,  498. 

17.  SASSE Vierteljahr.    f.   prak. 

Heilk.,  1866,  ii. 

18.  POKROWSKY  .  .   .  V.  A.  P.  A.,  xxii. 

19.  SIMON Animal    Chemistry!    Lon- 

don, 1845. 

20.  CUTLER  and  BRADFORD  .  A.  J.  M.  S.,  1878,  78. 


2T.    BUBNOW    . 
22.    MiJLLER  . 


.  Z.  P.  C.,  vii. 

.  V.  A.  P.  A.,  1901,  164,  436. 


MANGANESE. 

1.  PETREQCIN    .   .   .  Nouvelles    Recherches  du 

Manganese,  Paris,  1852 ; 
B.  G.  T.,  March,  1852. 

2.  GARROD M.  T.  G.,  1863. 

3.  LEAND     Gl.  M.  J.,  Jan.  1865. 

MINERAL   ACIDS. 

1.  KAZOWSKY    .   .   .  Centralb.  f.  Allg.  Path.  u. 

Path.  Anat.,  1894,  v. 

2.  CURTIN P.  M.  T.,  iii.  649. 

3.  PREYER C.  M.  W.,  1875,  578. 


FAMILY   III.— ALTERATIVES. 


THERE  are  employed  by  practitioners  of  medicine,  to  affect  certain 
-diseases  most  intimately  connected  with  the  processes  of  nutrition,  vari- 
ous substances  which  do  not,  at  least  in  the  doses  commonly  used,  pro- 
duce any  very  obvious  symptoms.  It  is  to  medicines  of  this  character 
that  the  name  of  Alteratives  has  been  applied,  because  when  adminis- 
tered they  seem  simply  to  alter  morbid  processes. 

Speculation  has  been  rife  as  to  the  mode  in  which  alteratives  influence  the 
body  ;  and  as  the  accepted  pathology  has  been  humoralistic  or  otherwise,  so  has  it 
been  strenuously  argued  that  they  act  upon  the  vital  fluid,  or  upon  the  solids  of  the 
body.  The  term  "  purifying  of  the  blood"  has  been  especially  applied  to  their 
action,  and  is  sufficiently  suggestive  of  their  function  as  viewed  from  the  pathologi- 
cal stand-point  of  the  old  humoralist.  What  we  know  of  the  action  of  these  medi- 
cines at  present  amounts  to  this,  that  they  modify  the  nutritive  processes  of  the 
body.  To  deny,  as  has  been  done,  the  existence  or  value  of  medicines  of  this 
class  because  we  cannot  tell  why  mercury  relieves  syphilis  or  why  potassium  iodide 
cures  rheumatism  is  as  absurd  as  to  deny  the  existence  of  the  syphilitic  and  the 
rheumatic  dyscrasia  because  we  do  not  know  their  ultimate  nature. 

PHOSPHORUS.     U.S. 

Phosphorus  is  a  translucent,  when  pure  nearly  colorless,  but  usually 
slightly  yellowish,  highly  inflammable  elementary  body,  which  is  taste- 
less, but  possessed  of  a  peculiar  alliaceous  odor.  It  is  insoluble  in  water, 
sparingly  soluble  in  ether,  absolute  alcohol,  and  the  oils,  freely  so  in 
chloroform.  It  takes  fire  at  100°  F. ,  and  melts  at  111.2°  F.  In  the 
shops  it  is  in  cylindrical  sticks,  covered  with  a  whitish  layer,  and  having 
when  cut  a  waxy  consistence  and  lustre.  It  occurs  in  several  allotropic 
forms, — red  phosphorus,  black  phosphorus,  and  the  crystallized  metallic 
phosphorus  of  Hittorf,  whose  physiological  properties  have  not  been 
investigated. 

PHYSIOLOGICAL  ACTION. — Absorption  and  Elimination. — It  has  of 
late  years  been  demonstrated  that  phosphorus  passes  into  the  blood  as 
phosphorus,  and  not  in  the  form  of  phosphoric  acid  or  other  compound. 

In  cases  of  poisoning  in  men  the  breath  is  said  to  be  sometimes  distinctly  phos- 
phorescent, and  in  animals  Bamberger  has  found  phosphorus  in  the  blood,  and 
Husemann  and  Marme  in  the  liver  two  or  three  hours  after  its  ingestion.  W.  Dyb- 
kowsky 28  has  detected  it  in  the  blood  and  liver  ten  hours  after  its  ingestion,  and 
other  observers  have  demonstrated  its  presence  in  almost  all  of  the  tissues.  It 
seems  probable  that  to  some  extent  it  finds  entrance  into  the  circulation  by  being 

459 


460  GENERAL  REMEDIES. 

dissolved  in  the  various  fatty  matters  contained  in  the  alimentary  canal.  At  the 
temperature  of  the  body,  however,  it  yields  abundant  vapors,  and  Bamberger  has 
demonstrated  that  these  readily  and  rapidly  pass  through  animal  membranes.  He 
has  found  that  defibrinated  blood,  when  separated  from  the  fumes  of  phosphorus 
only  by  an  animal  membrane,  rapidly  becomes  saturated  with  the  poison.  Dyb- 
kowsky  has  confirmed  this,  and  it  cannot  be  doubted  that  in  a  similar  manner  living 
blood  absorbs  the  poison  from  the  alimentary  canal.  W.  Dybkowsky's  research 
renders  probable  the  theory  of  Schuchardt w  that  the  phosphorus  is  converted  to 
some  extent  in  the  alimentary  canal,  but  much  more  largely  in  the  veins,  into  phos- 
phuretted  hydrogen,  and  that  some  of  this  compound  and  some  of  the  phosphorus 
itself  is  oxidized  in  the  venous  blood,  so  that  phosphoric  acid,  besides  phosphorus 
and  phosphuretted  hydrogen,  is  emptied  into  the  arterial  blood  ;  further,  that  the 
last  two  compounds  are  oxidized  at  the  expense  of  the  arterial  blood  and  the  tis- 
sues it  feeds,  and  that  the  poisoning  is  due  to  this  deprivation  of  oxygen.  For  the 
details  of  the  experiments  upon  which  these  conclusions  rest  we  must  refer  the 
reader  to  the  original  memoir.  *  According  to  Plaice,38  phosphorus  is  not  found  in 
free  condition  in  these  cases  in  the  urine. 

The  physiological  action  of  phosphorus  in  therapeutic  doses  is  prob- 
ably entirely  different  from  that  which  it  exerts  when  in  larger  amounts. 
It  is  a  constituent  of  most  of  the  more  important  tissues,  and  is  especially 
abundant  in  the  nerve-centres,  upon  whose  nutrition  it  is  believed  by 
many  to  act  as  a  stimulant.  So  far  as  the  nervous  system  is  concerned, 
this  assertion  rests  upon  clinical  observation  ;  but  Wegner l  (confirmed  by 
S.  Miura  and  W.  Stoeltzner 2)  has  experimentally  demonstrated  such  an 
action  upon  the  bony  tissues.  When  adult  animals  are  fed  upon  minute 
doses  of  phosphorus  the  spongy  tissue  in  the  long  and  short  bones  becomes 
thickened  and  the  compact  tissue  more  dense.  After  a  time  new  tissue  is 
deposited  upon  the  inside  of  the  shafts  of  the  long  bones,  in  some  instances 
until  the  marrow  cavity  is  obliterated.  The  action  upon  the  bones  of 
growing  animals  is  even  more  marked. 

Phosphorus  was  at  one  time  believed  to  be  a  diffusible  stimulant,  and 
it  possibly  may  exert  such  an  influence.  In  the  acute  nervous  exhaustion 
of  typhoid  pneumonia  we  have  once  or  twice  seen  it  apparently  act  favor- 
ably in  this  way. 

For  reasons  to  be  already  adduced  (see  page  459),  it  is  certain 
that  in  poisonous  doses  phosphorus  enters  the  blood  in  its  elemental 
form.  Wegner  advances  the  following  reasons  for  believing  that  thera- 
peutic doses  act  as  phosphorus  upon  the  bony  tissues.  First,  no  similar 
action  can  be  obtained  from  phosphoric  acid  unless  from  eight  hundred 
to  one  thousand  times  the  proportional  dose  be  given.  Second,  the 
newly  formed  tissue  is  at  first  gelatinous.  Third,  there  is  no  excess  of 
phosphates  in  the  bone.  Fourth,  when  the  food  is  deprived  of  lime  the 
same  new  tissue  arises,  but  remains  in  a  soft,  gelatinous  state. 

THERAPEUTICS. — The  chief  use  of  phosphorus  in  medicine  is  as  a 
nutrient  tonic  to  the  nervous  system.  In  all  cases  of  chronic  nervous 

*  M.  Lecorch£  (Archives  de  Physiologic  Normale  et  Pathologique,  1868,  i.,  1869,  ii.) 
believes  that  phosphorus  acts  in  the  blood  as  phosphoric  acid,  but  does  not  establish  his 
opinion.  For  a  discussion  of  this,  see  Dybkowsky's  paper. 


ALTERATIVES.  461 

exhaustion,  whether  involving  the  cerebral  or  the  spinal  centres,  it  is  of 
great  value  ;  even  when  the  symptoms  strongly  suggest  organic  disease, 
as  in  threatening  cerebral  softening  or  myelitic  paraplegia  from  excessive 
venery,  it  is  often  of  service.  It  has  been  strongly  extolled  in  neuralgia 
due  to  nervous  exhaustion. 

It  is  probable  that  it  may  be  of  value  in  some  cases  of  impaired 
vitality,  although  the  nervous  system  be  not  obviously  implicated.  H. 
Eames 3  states  that  he  has  obtained  great  benefit  from  its  use  in  obstinate 
skin  affections,  such  as  lupus,  acne,  and  psoriasis.  S.  R.  Percy*  has 
used  it  successfully  for  repeated  furuncular  eruptions.  It  has  also  been 
asserted  to  be  useful  in  cataract* 

On  account  of  its  marked  influence  on  the  development  of  bone, 
Wegner  suggested  its  use  in  osteomalacia  and  in  rickets,  and  thereby 
started  a  large  amount  of  clinical  experimentation  and  a  considerable 
clinical  literature,  in  which  there  is  some  contradiction  :  the  general  re- 
sult, however,  has  been  to  establish  the  value  of  the  drug  in  rachitic 
cases,  especially  in  those  in  which  there  is  a  tendency  to  osteoporosis.  As 
large  doses  as  can  be  borne  without  derangement  of  the  digestion  should 
be  given. 

TOXICOLOGY. — The  ingestion  of  a  fatal  dose  of  phosphorus  is  not 
followed  by  any  sensible  effects  for  some  time.  After,  however,  from 
three  to  twelve  hours  a  sense  of  weakness  and  of  general  wretchedness 
manifests  itself,  and  in  a  large  proportion  of  the  cases  (according  to 
Lewin,  eighty-eight  per  cent.)  is  accompanied,  or  soon  followed,  by 
vomiting.  With  the  emesis  there  is  nausea,  and  in  most  cases  the 
patient  soon  complains  of  abdominal  pain,  the  severity  of  which,  how- 
ever, never  equals  that  of  corrosive  poisoning.  The  matters  vomited 
consist  of  food,  mucus,  and  bile.  During  the  first  eight  or  ten  hours 
they  often  smell  strongly  of  phosphorus,  and  are  luminous  in  the  dark. 
The  vomiting  may  persist  during  the  whole  attack,  but  generally  ceases 
on  the  second  or  third  day,  to  reappear  with  the  subsequent  jaundice, 
when  coffee-colored  vomit  from  exuded  blood  is  ejected.  The  pain, 
which  in  most  cases  abates  with  the  vomiting,  often  spreads  from  the 
epigastrium  over  the  whole  abdomen,  and  in  rare  instances  is  parox- 
ysmal. If  it  reappear  in  the  latter  stages,  it  is  apt  to  affect  especially  the 
right  hypochondrium,  and  is  associated  with  decided  tenderness  in  the 
region  named  and  in  the  epigastrium. 

In  the  very  acute  cases  of  phosphorus-poisoning  a  primary  condition 
of  pronounced  cardiac  weakness,  passing  into  paralysis,  may  be  present ;  f 
in  the  subacute  cases  the  heart-muscle  undergoes  so  much  degeneration 
that  a  slowly  developed  but  progressive  cardiac  weakness  is  produced 
and  may  be  the  cause  of  death. 


*  Tavignot  (Revue  de  Therapeutique  Medico-Chirurgicale,  August  and  September, 
1871)  and  Gioppi  (Giornale  d' Oftalmologia,  abstract  in  N.  Y.  Medical  Record,  1873). 
t  See  especially  J.  Pal  (Jahrb.  d.  Wiener  k.  k.  Krankenaushalten,  1896,  ix.  43). 


462  GENERAL  REMEDIES. 

The  tongue  is  whitish  or  abnormally  red,  sometimes  furred.  There 
are  generally  fever,  loss  of  appetite,  and  thirst.  Maukopff  has  noted  a 
morning  and  evening  temperature  of  from  37°  C.  to  39°  C.  and  from 
37.4°  C.  to  39.8°  C.  respectively.  Later  in  the  poisoning  there  is  very 
often  a  remarkable  fall  in  the  temperature,  which  is  generally,  but  not 
always,  a  precursor  of  death.  The  lowest  point  we  have  seen  noted  was 
31.2°  C.  (88.2°  F. )  some  hours  before  death.*  In  some  cases  fever  is 
altogether  absent,  or  comes  on  just  before  death,  f 

The  stools  are  at  times  normal  in  character  and  frequency,  but  there 
is  general  diarrhoea  or  constipation,  with  flatulence.  Late  in  the  attack 
the  passages  are  in 'most  cases  very  light  clay-colored,  or  even  whitish, 
and  exceptionally  they  are  bloody.  In  some  cases  they  are  phospho- 
rescent. 

Jaundice  comes  on  in  from  thirty-six  hours  (cases  reported  by  Mau- 
kopff5 and  by  Tiingel6)  to  five  days  (Lebert  and  Wyss7)  after  the  inges- 
tion  of  the  poison.  In  most  cases  it  appears  first  in  the  conjunctiva,  but 
sometimes  the  urine  gives  previous  warning  of  its  approach.  In  some 
cases  there  is  with  it  a  decided  and  palpable  increase  in  the  size  of  the 
liver,  which  may  pass,  if  the  patient  live  long  enough,  into  an  equally 
apparent  lessening  of  the  bulk  of  that  viscus.  The  severe  nervous  symp- 
toms are  rarely,  if  ever,  developed  until  after  the  jaundice,  although 
early  in  the  attack  there  are  not  infrequently  anxiety,  headache,  giddiness, 
and  dreamy  unquiet  sleep,  or  even  sleeplessness.  The  more  pronounced 
nervous  symptoms  consist  of  delirium,  which  may  be  wild  and  is  very 
frequently  erotic,  with  somnolence  ending  in  coma  and  death,  occasion- 
ally preceded  by  convulsions.  According  to  Taylor,  the  latter  are  a  cer- 
tain sign  of  approaching  dissolution.  Very  generally  partial  spasms  and 
fibrillary  contractions  of  the  voluntary  muscles  occur,  although  there  is 
always,  in  not  too  rapid  cases,  progressive  paresis  of  the  voluntary  mus- 
cles. Death  is  usually  put  off  beyond  twenty-four  hours,  yet  it  has 
occurred  in  a  child  in  four  hours  and  in  an  adult  in  seven8  hours  ;  also  in 
nine 9  hours.  The  patient  may  suddenly  succumb  to  collapse  and  cardiac 
paralysis,  but  more  commonly  dies  comatose  from  a  gradual  failure  of 
respiration  and  circulation. 

If  recovery  occur  it  is  by  a  gradual  amelioration  of  the  symptoms, 
and  the  health  of  the  patient  is  apt  to  be  impaired  for  some  time, 
the  most  marked  disturbances  usually  being  the  digestive  and  nervous 
symptoms.  Apparently  desperate  cases  will  sometimes  convalesce  unex- 
pectedly, and  Tiingel  states  that  a  favorable  issue  may  take  place  even 
after  violent  delirium. 

The  urine  is  almost  always  much  affected  by  the  poison.  Very  com- 
monly it  is  scanty  or  albuminous,  and  sometimes  it  contains  sugar.  J  As 

*  Battmann  (Archiv  der  Heilkunde,  1871,  257). 
t  Concato  (Sydenham  Soc.  Year- Book,  1869-70,  454)- 

%  In  only  six  of  one  hundred  and  forty-one  consecutive  cases  of  phosphorus 
poisoning  in  the  Medical  Clinic  of  Prague  was  sugar  found  in  the  urine  (Zeitschr.  f. 


ALTERATIVES.  463 

was  first  pointed  out  by  Munk  and  Leyden,10  after  jaundice  has  set  in, 
bile-acids,  as  well  as  biliary  coloring-matter,  are  always  to  be  found  in  the 
urine.  Not  infrequently  a  cloudy  sediment  consisting  in  part  of  epithe- 
lial cells,  often  tinged  with  bile,  is  deposited.  Oswald  Kohts  n  and  other 
observers  have  found  leucin  and  tyrosin  in  the  urine  of  dogs  poisoned 
with  phosphorus,  and  undoubtedly  these  substances  may  occur.  Wohl- 
gemuth 39  has  found  besides  these  bodies  arginin  in  the  urine  of  a  rabbit 
poisoned  with  phosphorus.  The  albuminuria  generally  follows,  but 
may  precede  the  icterus.  A  very  remarkable  and  apparently  con- 
stant constituent  of  the  urine  is  sarcolactic  acid.  Fat  has  been  found 
in  the  urine  inside  of  renal  epithelial  cells,  and  also  as  free  globules 
(Schultz12). 

Aberrant  Poisoning. — In  some  instances  phosphorus-poisoning  presents 
symptoms  quite  different  from  the  typical  array.  Death  may  take  place  in  a  few 
hours,  and  in  such  cases  jaundice  is  not  generally  present.13  Zeidler  reports  a 
death  in  forty-two  hours,  from  suppression  of  urine,  with  collapse  and  erotic  de- 
lirium. In  a  case  of  Bellinger's u  the  chief  symptoms  were  vomiting,  pain  and 
tenderness  over  the  abdomen,  great  weakness  of  pulse,  gradually  developed  pa- 
ralysis of  the  legs,  and  death,  without  jaundice,  in  four  and  a  half  days.  The 
autopsy  revealed  hemorrhagic  effusion  between  the  membranes  and  the  spinal 
cord,  and  also  into  the  sheaths  of  the  proximal  portions  of  the  spinal  nerves. 

In  women,  fatal  doses  of  phosphorus  very  commonly  produce  a  bloody  pseudo- 
menstrual  discharge,  or,  when  pregnancy  exists,  abortion.  M.  Miura 15  has  found 
in  the  foetus  of  poisoned  rabbits  structural  changes  similar  to  those  of  the  mother. 

Sub-acute  phosphorus-poisoning  is  said  sometimes  to  be  manifested  by  sym- 
metrical gangrene  of  the  extremities.  (See  W.  K.  W.,  1901,  No.  52.) 

Post- Mortem  Appearances. — The  post-mortem  lesions  found  after  death 
from  phosphorus-poisoning  are  quite  characteristic,  consisting  of  wide- 
spread fatty  degenerations  involving  practically  all  of  the  organs,  but 
especially  marked  in  the  gastro-intestinal  mucous  membrane,  the  liver, 
and  the  kidney. 

As  was  first  pointed  out  by  Virchow,16  there  is  universally  a  gastro-adenitis, 
which  causes  the  gastric  mucous  membrane  to  become  thickened,  opaque,  whitish, 
grayish,  or  yellowish-white.  This  gastro-adenitis  is  not  due  to  a  local  action  of  the 
phosphorus,  because  it  occurs  when  the  poison  is  introduced  through  other  chan- 
nels than  the  mouth.  The  duodenum  and  intestines  suffer  similar  changes. 

The  liver  is  generally  very  much  enlarged,  friable,  and  light-colored  ;  some- 
times it  is  mottled,  .and  sometimes  portions  of  it  are  deeply  stained  with  bile.*  The 
cells  are  gorged  with  fat-globules,  f  and  in  some  cases  there  are  small-celled  inter- 

Heilkde.  N.  F.,  ii.  8  u.  9,  p.  339,  1901).  As  originally  stated  by  von  Jaksch,  the  sugar  is 
probably  of  secondary  origin,  due  to  the  alterations  of  the  liver. 

*  According  to  researches  made  by  Emile  Rousseau  in  the  Pathological  Laboratory 
of  the  University  of  Pennsylvania,  the  first  anatomical  changes  in  the  liver  occur  in  the 
centre  of  the  lobules  around  the  hepatic  vein. 

t  A.  Lebedeff  (Arch.  f.  Physiol.,  1883,  xxxi.  n)  believes  that  the  fat  in  the  liver  is 
not  produced  by  degeneration  of  the  hepatic  tissue,  but  has  simply  been  transported  there 
from  the  subdermal  regions.  He  bases  this  opinion  upon  his  own  observations, — first, 
that  the  phosphorus  fat  has  the  same  chemical  constitution  as  has  subdermal  fat ;  second,  in 
a  dog  which  had  been  fed  with  linseed  oil  and  then  poisoned  with  phosphorus,  the  liver 
was  loaded  with  linseed  oil.  This  evidence  is  of  very  little  value,  because  on  the  one 


464  GENERAL  REMEDIES. 

stitial  thickenings  due  to  hyperplasia  of  the  trabecular  tissue.  The  gall-bladder 
may  be  full  or  empty.  In  protracted  cases  the  liver  undergoes  atrophy,  with 
destruction  of  its  secreting  cells.  According  to  the  researches  of  Arthur  Heffter,17 
the  percentage  of  lecithin  in  the  liver,  which  is  fixed  in  health,  is  greatly  lessened 
in  phosphorus-poisoning.  The  kidneys,  especially  in  their  cortical  portion,  suffer 
a  degeneration  similar  to  that  of  the  liver,  the  epithelium  becoming  enlarged, 
granular,  fatty,  and  finally  undergoing  destruction.  The  voluntary  and  cardiac 
muscles,  the  spleen,  the  lungs,  and  probably  all  the  tissue,  partake  of  the  universal 
fatty  degeneration  *  which  Wegner  has  shown  to  involve  even  the  minute  arterioles. 

The  nervous  system  does  not  escape.  As  long  ago  as  1880  Danillo  declared 
that  he  had  found  a  myelitis  in  phosphorus-poisoning,  and  Gurrieri18  has  dis- 
covered in  the  poisoned  dog  degenerations  of  various  portions  of  the  spinal  cord  ; 
whilst  it  has  been  shown  by  Uziemblo  t  that  profound  alterations  take  place  in  the 
retina,  which  becomes  o^dematous,  with  marked  alterations  in  the  vessels,  hemor- 
rhagic  extravasations,  and  necrotic  degeneration  of  the  nervous  cells. 

The  blood  is  often  profoundly  affected,  |  becoming  very  dark,  more  or  less 
completely  losing  its  power  of  coagulation,  §  and  apparently  suffering  also  in  its 
corpuscular  elements  ;  ecchymoses  are  almost  universal,  and  haematin  crystals 
are  occasionally  found  in  the  viscera.  The  ecchymoses  occur  in  all  parts  of  the 
body,  but  are  apt  to  be  especially  pronounced  in  the  mediastinum  and  the  serous 
membranes.  Schiff 19  has  found  that  in  dogs,  after  death  from  phosphorus,  the  blood 
does  not  pass  into  the  veins,  but  remains  in  the  arteries.  O.  Silbermann  *°  states 
that  thrombi  are  formed  in  the  blood-vessels  ;  and  it  has  been  shown  by  G.  Puppe 
that  these  are  very  common  in  slow  cases  of  the  poisoning,  and  are  of  fatty  nature. 

It  should  be  remembered  that  although  some  or  all  of  the  lesions 
which  have  just  been  described  are  usually  found  in  the  bodies  of  persons 
dead  of  phosphorus-poisoning,  it  is  possible  for  the  poison  to  take  life 
very  rapidly  and  leave  no  trace  of  its  influence,  there  being  not  even 

hand  the  linseed  oil  probably  accumulated  in  the  dog's  liver  before  the  poisoning  and 
simply  remained  over,  and  on  the  other  hand  there  is  no  proof  that  fat  produced  by  de- 
generative changes  necessarily  differs  in  composition  from  other  fat.  The  fact  that  the 
liver  and  other  organs  are  destroyed  in  phosphorus- poisoning  may  be  considered  proof  that 
the  fat  is  formed  out  of  the  affected  tissue ;  although  this  seems  contrary  to  the  allegation 
of  Bergeat  ( Gesellsch.  f.  Morph.  u.  Physiol.  Miinchen.,  1888),  that  in  very  emaciated 
animals  the  phosphorus-poisoning  may  run  its  course  without  the  formation  of  fat. 

*  For  full  discussion  of  the  pathology  of  phosphorus-poisoning,  see  H.  Lebert  and  O. 
VVyss  (Archives  Gen.,  September,  1868),  Otto  Bellinger,  also  O.  Kohts  (Deutsches  Archiv 
f.  Klin.  Med.,  1869,  v.).  Ziegler  (Beitrage  Path.  Anat.,  ii.),  G.  Kronig  (  Virchow's  Archiv, 
1887,  ex.),  Aufrecht  (Deutsch.  Arch.  Klin.  Med.,  1897,  Iviii.),  HansSchmaus  (Miinchener 
Med.  Wochensch.,  1897,  xliv.,  also  1898,  xlv.),  Hans  Schmaus  and  Arthur  Boehm  (Arch, 
f.  Path.  Anat.,  1898,  clii.).  See  also  Schmidt's  Jahrbiic her,  cclvii.,  94. 

t  See  Uziemblo  ( Die  Pathologischen  Alterationen  der  Retina  bei  Phosphovergiftung, 
Monographic,  St.  Petersburg,  1892,  Russisch),  also  Julius  Steinhaus  (Beitrage  zur  Path- 
ologischen Anatomic  und  zur  Allgemeinen  Pathologie,  xxii.). 

J  Mayr  states  that  when  very  large  doses  of  the  poison  have  been  taken  the  blood 
and  even  the  urine  (?)  may  be  phosphorescent  (Canstatfs  Jahresbericht,  1862,  v.  123). 
Otto  Taussig,  as  the  result  of  a  series  of  blood  studies  in  phosphorus-poisoning,  reaches  the 
somewhat  remarkable  conclusion  that  in  man,  usually  at  about  the  acme  of  the  symptoms, 
there  is  either  a  suddenly  developed  or  a  slowly  produced  increase  of  the  red  blood-cor- 
puscles, without  an  increase  of  the  haemoglobin  of  the  blood  and  with  a  distinct  lessening 
of  the  leucocytes,  whereas  in  the  rabbit  there  is  no  alteration  in  the  amount  of  haemoglobin 
or  number  of  red  disks,  but  a  plain  increase  of  the  white  corpuscles  ;  and  in  chickens  there 
occurs  an  enormous  destruction  of  the  red  disks,  with  a  marked  leucocytosis  (Archiv f. 
Exper.  Path.  u.  Pharm.,  1892,  30). 

§  See  Corin  and  Ansiaux  (  Viertelj.f.  gerichtl.  Med.,  1894,  vii.). 


ALTERATIVES.  465 

sarcolactic  acid  in  the  urine  (see  case  reported  by  Paltauf 21).  According 
to  the  researches  of  W.  W.  Podwyssotsky,22  in  rapid  cases  the  first 
change  in  the  body  consists  in  the  formation  of  little  whitish-yellow  ne- 
crotic  foci  in  the  liver.  The  anatomical  changes  in  the  liver  in  phos- 
phorus-poisoning are  sufficient  to  confirm  the  statements  of  Schultzen 
and  Riess,  that  in  the  poisoning  there  is  arrest  of  glycogen  and  sugar 
formation. 

The  elimination  of  bile  acids  in  the  urine  shows  that  the  jaundice  of  phos- 
phorus is  caused  not  by  an  arrest  of  secretion,  but  by  an  occlusion  of  the  biliary 
passages  and  consequent  resorption  of  the  bile.*  O.  Kohts  has  apparently  demon- 
strated that  the  occlusion  is  most  frequently  due  to  the  duodenitis  involving  the 
common  duct,  so  as  to  obliterate  its  lumen  by  the  swelling  of  the  mucous  membrane. 
In  some  cases,  however,  it  is  probable,  as  believed  by  Wyss,  Alter,  and  Ebstein, 
that  a  catarrhal  inflammation  of  the  minute  gall-ducts  is  the  cause  of  the  jaundice, 
and  also  that  the  result  is  in  part  effected  through  pressure  upon  those  ducts  by  the 
swelling  of  the  glandular  and  trabecular  tissue. f  It  is  proper  to  state  that  Demar- 
baix 23  and  Willmart 24  insist  that  the  icterus  is  not  really  hepatogenous,  but  haemic  in 
origin,  chiefly  because  they  have  found  haematoidin  in  the  urine.  This  fact,  how- 
ever, proves  only  that  the  blood  is  altered  by  the  poison  :  it  does  not  disprove  the 
liver  origin  of  the  jaundice. 

Acute  phosphorus-poisoning  so  closely  resembles  yellow  atrophy  of 
the  liver  that  their  clinical  distinction  is  sometimes  difficult,  nay,  impossi- 
ble. Distinct  phosphorescence  in  the  breath,  vomit,  or  stools  would,  of 
course,  be  direct  evidence  of  poisoning.  This  phosphorescence,  however, 
very  often  cannot  be  detected  :  according  to  Vetter,25  it  can  be  rendered 
more  evident  in  the  vomit,  stools,  etc. ,  by  acidifying  with  sulphuric  acid 
and  warming  in  a  shallow  dish.  When  death  ensues  during  the  first 
week  of  phosphorus-poisoning,  the  enlarged  liver  affords  a  distinctive 
proof  of  poisoning  ;  but  when  the  case  is  more  protracted,  the  atrophied 
liver  of  phosphorus  cannot  be  distinguished  from  that  of  the  natural  dis- 
ease. Phosphorus-poisoning  usually  develops  more  abruptly  than  does 
acute  yellow  atrophy,  and  the  primary  disturbance  of  the  stomach  is 
more  severe,  whilst  the  lull  of  the  symptoms  is  more  complete.  The 
clinical  differences,  however,  between  various  cases  of  either  affection  are 
greater  than  those  which  have  been  relied  upon  as  separating  the  two 
affections.  Kohler  has  asserted  that  oxymandelic  acid  in  atrophy  of 
the  liver  replaces  the  sarcolactic  acid  of  phosphorus-poisoning,  and 

*  E.  Stadelmann  (Archivf.  Exper,  Path.  u.  Pharm.,  1888,  xxiv.)  states,  as  the  result 
of  his  experiments  made  upon  dogs,  that  so  far  as  the  secretion  of  bile  is  concerned  three 
stages  can  be  made  out.  In  the  first  stage  there  are  irritation  of  the  liver  and  increase  of 
the  formation  and  excretion  of  biliary  coloring-matter ;  in  the  second  stage  the  gall  be- 
comes mucous  and  cloudy,  and  the  production  and  separation  of  biliary  coloring-matter  are 
lessened  (it  is  in  this  stage  that  the  icterus  begins) ;  in  the  third  stage  the  gall  becomes 
again  clear,  dark,  and  more  rich  in  biliary  coloring-matter,  so  that  the  normal  excretion 
of  biliary  coloring-matter  is  notably  surpassed. 

t  For  an  elaborate  discussion  of  the  cause  of  jaundice,  see  Kohts's  paper  (Deutsches 
Archiv  f.  Klin.  Med.,  \.  168) ;  also  that  of  Bellinger  (Centralbl.  f.  die  Med.  Wiss.,  1869, 
and  Deutsches  Archivf.  Klin.  Med.,  1869.  v.). 

30 


466  GENERAL  REMEDIES. 

stress  has  been  laid  upon  the  asserted  facts  that  in  the  natural  disease 
leucine  and  tyrosine  are  present  in  abundance  in  the  urine,  while  in  the 
poisoning  they  are  absent.  In  yellow  atrophy,  however,  tyrosine  is  not 
infrequently  absent  from  the  urine  and  leucine  present  in  very  small 
amount,  while  both  principles  may  be  present  in  phosphorus-poisoning.* 
In  regard  to  the  acids  in  the  urine,  very  careful  chemical  analysis  would 
in  any  case  be  necessary  to  determine  their  presence,  and  sufficient  evi- 
dence is  certainly  not  yet  forthcoming  to  show  that  either  of  them  is 
really  characteristic.  Chemical  examination  is  therefore  absolutely  neces- 
sary in  all  medico-legal  cases,  f  According  to  M.  Poulet,26  phosphorus  is 
eliminated  as  hypophosphoric  acid,  and  the  poisoning  can  be  recognized 
by  heating  the  urine  with  nitric  acid  to  calcination.  If  hypophosphoric 
acid  be  present,  as  dryness  is  reached  the  mixture  suddenly  bursts  into  a 
flame  like  a  packet  of  matches. 

The  cause  of  death  in  phosphorus-poisoning  is  probably  the  wide- 
spread structural  alterations,  as  the  experiments  of  A.  Hauser27  indicate 
that  the  poison  does  not  act  by  inhibiting  life  processes. 

The  indications  for  treatment  in  phosphorus-poisoning  are  very  evi- 
dent. It  is  plain  that  no  medication  can  influence  the  terrible  organic 
lesions  induced,  and  that  the  primary  object  must  be  to  prevent  the  ab- 
sorption of  the  poison.  Emetics  and  purgatives  are,  therefore,  of  prime 
importance.  The  necessity  of  the  persistent  use  of  evacuants  is  shown 
by  the  finding  of  phosphorus  by  Starck 28  in  the  stools  three  and  a  half 
days,  and  in  the  vomit  two  days,  after  the  ingestion  of  the  fatal  dose. 
As  phosphorus  is  soluble  in  oils,  no  fatty  matters  should  be  allowed  either 
in  the  food  or  in  the  medicines.  As  an  emetic,  copper  sulphate  shoztld 
always  be  chosen. 

The  minute  particles  of  phosphorus  adhere  so  closely  to  the  ali- 
mentary canal  that  they  cannot  be  dislodged  by  mechanical  means,  and 
an  antidote  is  urgently  demanded.  For  the  purpose  of  oxidizing  the 
poison,  Duflos  suggested  calcined  magnesia  and  chlorine-water,  and 
Scherer  the  chlorinated  lime  ;  but  in  practice  these  substances  have  been 
found  of  no  value,  on  account  of  the  slowness  of  their  action. 

The  oil  of  turpentine,  originally  proposed  by  Andant*9  as  an  anti- 
dote to  phosphorus,  J  has  been  largely  used  by  experimenters,  with 
apparently  contradictory  results,  which,  as  is  now  known,  were  due  to 
the  employment  of  different  varieties  of  the  oil. 

*  Cases  (Wiener  Med.  Presse,  1872;  Schmidt's  Jahrb.,  clxix.  127,  cxcv.  123).  Ossi- 
kovsky  believes  that  the  principles  appear  habitually  about  the  sixth  day  of  the  poison- 
ing, when  the  liver  is  still  enlarged. 

t  For  discussions  of  the  diagnosis  between  yellow  atrophy  and  phosphorus-poisoning, 
see  Kohler  (Syd.  Soc.  Year-Book,  1870,  455),  Schultzen  and  Ries  (Annalen  des  Berlin. 
Krankenhauses,  1869,  xv.),  and  especially  I.  Ossikovsky  (Wien.  Medizin.  Presse,  1872, 
xiii.,  abstracted  in  Schmidt's  Jahrb.,  cliv.  15).  For  cases  in  which  the  question  was 
legally  raised,  investigated,  and  discussed,  see  Schmidt's  Jahrb.,  cxli.  167 ;  Syd.  Soc.  Year* 
Book,  1832,  430;  Annales  d' Hygiene,  Jan.  1869. 

J  For  cases,  see  Gazette  ffebdomadaire,  1874;  Schmidt's  Jahrbiicher,  clxix,  126; 
Med.  Times  and  Gaz.,  1876,  ii.  461. 


ALTERATIVES.  467 

There  are  in  European  commerce  three  varieties  of  turpentine, — the  rectified, 
the  German,  and  the  French.  Jonas30  found  that  while  the  pure  oil  has  no  effect 
upon  phosphorus,  the  acid  French  oil  forms  with  it  a  crystalline,  spermaceti-like 
mass.  This  is  soluble  in  ether,  alcohol,  and  alkaline  solutions,  and  has  received 
the  name  of  turpentine-phosphoric  acid.  It  is  said  to  be  eliminated  by  the  kidneys 
unchanged,  and  to  exert  no  deleterious  influence.  The  elaborate  experiments  of 
Vetter  on  dogs  and  rabbits  gave  results  in  accord  with  these  facts,  for  he  found  the 
rectified  and  German  oils  to  be  of  no  value  in  phosphorus-poisoning,  while  the  crude 
acid  French  oil  was  distinctly  antidotal.  Kochler,  however,  asserts  that  when  the 
German  oil  has  not  been  rectified  for  some  time,  it  acts  upon  phosphorus.  He 
believes  that  the  oil  acts  partly  by  oxidizing  the  poison  and  partly  by  converting  it 
into  the  harmless  turpentine-phosphoric  acid.  One  part  of  the  oil  must  be  given 
for  o.oi  part  of  the  phosphorus.31  Case  of  recovery.32  See  also  Bene.33 

Ordinary  American  oil  of  turpentine  and  Canada  balsam  are  of  no 
value  in  phosphorus-poisoning. 

As  was  pointed  out  by  Eulenburg  and  Guttmann,34  and  subsequently 
by  Bamberger,85  phosphorus  in  a  solution  of  a  soluble  salt  of  copper 
becomes  immediately  black,  owing  to  the  formation  of  a  phosphide  of 
the  metal.  Bamberger  also  asserts  that,  while  this  change  is  very  rapid, 
that  induced  by  turpentine  is  a  slow  one,  and,  from  an  elaborate  series  of 
experiments  upon  animals,  concludes  that  copper  is  much  the  more  valu- 
able and  certain  antidote.  Antal  appears  to  have  been  the  first  to  use 
potassium  permanganate  as  an  antidote  to  phosphorus,  and  in  a  series 
of  experiments  upon  dogs  E.  Q.  Thornton36  found  it  much  superior  to 
cupric  sulphate.  Hydrogen  dioxide  appeared  in  Thornton's  experi- 
ments to  be  valueless.  In  human  poisoning  cupric  sulphate  should  be 
given  in  dilute  solution,  three  grains  every  five  minutes  until  vomiting  is 
induced.  After  this  the  potassium  permanganate  should  be  freely  admin- 
istered, or,  as  was  successfully  done  by  Hajinos,  the  stomach  may  be 
washed  out  with  its  solution  ;  later,  the  magnesium  sulphate  or  citrate 
may  be  given  as  a  quickly  acting  purge,  and  symptoms  met  as  they 
arise.* 


*  We  have  allowed  the  text  to  stand  as  in  the  old  edition  because  of  the  present 
uncertainty  as  to  the  comparative  values  of  the  use  of  copper  sulphate  and  potassium 
permanganate.  In  the  United  States  phosphorus-poisoning  is  very  rare :  we  have  not 
met  with  more  than  one  or  two  reported  cases.  In  Continental  Europe,  however,  prob- 
ably on  account  of  the  difficulty  of  obtaining  poisons  through  the  restrictions  of  the  law, 
phosphorus  is  perhaps  the  most  used  of  any  poison  for  the  purpose  of  suicide.  Thus, 
out  of  forty  cases  of  attempted  self-murder,  brought  to  the  Prager  clinic  between  1889  and 
1895,  in  thirty-nine  the  phosphorus  contained  in  the  heads  of  matches  had  been  employed 
(Fr.  Lanz,  Berl.  Klin.  Wochensc.hr.,  1895,  xxxiii.).  Formerly  the  treatment  at  the  clinic 
consisted  in  washing  out  the  stomach  with  warm  water  until  the  smell  of  phosphorus  dis- 
appeared ;  then  continuing  the  washing  with  water  containing  copper  sulphate  and  cal- 
cined magnesia,  and  following  up  by  giving  internally  copper  sulphate  and  oil  of  turpen- 
tine ;  also  large  doses  of  sodium  bicarbonate.  Since  1893,  when  the  Antal  method  was 
introduced,  the  plan  has  been  to  wash  out  the  stomach  with  large  quantities  of  one-eighth 
per  cent,  solution  of  the  permanganate  ;  then  administer  one  litre  of  the  one-half  per  cent, 
solution,  at  the  same  time  giving  a  purgative  ;  on  the  following  day  giving  large  doses  of 
sodium  bicarbonate  with  the  oil  of  turpentine.  The  mortality  per  cent,  of  the  cases  before 
the  change  of  treatment  was  36.6 ;  since  the  change  of  treatment,  41 .6 — a  result  which  is 
not  favorable  to  the  newer  method. 


468  GENERAL  REMEDIES. 

Chronic  Poisoning. — Match-makers  and  other  artisans  who  are  ex- 
posed by  their  occupations  to  the  fumes  of  phosphorus  suffer  from  chronic 
poisoning,  which  is  especially  distinguished  by  the  occurrence  of  ne- 
crosis of  the  upper  or  lower  jaw.  It  occurs  chiefly  in  those  artisans 
who  have  bad  teeth,  and  the  experiments  of  Wegner  have  demonstrated 
that  the  necrosis  of  the  jaw  is  due  to  the  local  action  of  the  vapor  of 
phosphorus.* 

Wegner  found  that  when  rabbits  were  kept  in  an  atmosphere  full  of  the  fumes 
of  the  poison  no  necrosis  ever  occurred,  unless,  by  means  of  an  unsound  tooth  or 
an  artificial  wound,  the  atmosphere  had  access  to  the  bone.  If  such  access  were, 
on  the  other  hand,  allowed  to  any  bone  of  the  body,  periostitis  and  subsequent 
necrosis  resulted.  Further,  when  rabbits  received  continuously  small  doses  of  the 
phosphorus  by  the  mouth,  no  necrosis  occurred  even  after  wounds  which  laid  bare 
the  bones. 

ADMINISTRATION. — A  useful  preparation  of  phosphorus  is  the  elixir 
(ELIXIR  PHOSPHORI,  U.  S. ,  1890),  one  drachm  containing  about  one- 
sixty-fifth  of  a  grain  (o.ooi  Gm. )  of  phosphorus.  Dose,  twenty  to  forty 
minims  (1.2-2.5  C.c. ).  Phosphorated  oil  (OLEUM  PHOSPHORATUM, 
U.  S.  1890)  contained  one-hundred-and-fifteenth  of  a  grain  of  phos- 
phorus to  the  minim.  Dose,  one  to  three  minims  (0.003-0. 1 8  C.c. ). 
Each  pill  of  phosphorus  (PiLUL^E  PHOSPHORI,  U.  S. )  contains  about  one 
hundreth  of  a  grain  (o.  0006  Gm. ) 

The  dose  of  phosphorus  may  be  set  down  as  from  the  one-hundredth 
to  the  one-fiftieth  of  a  grain,  increased  unless  gastric  disturbance  is  pro- 
duced. J.  A.  Thompson  affirms  that  he  has  given  one-fourth  of  a  grain 
every  four  hours  without  injury.  Anstie  says  that  he  has  seen  slight  poi- 
soning produced  by  three-fourths  of  a  grain  taken  in  seven  days  in  divided 
doses.  It  is  always  wiser  to  have  a  freshly  made  preparation,  as  phos- 
phorus in  solution  or  in  pill  is  very  prone  to  undergo  oxidation. 

ZINCI  PHOSPHIDUM. — Zinc  Phosphide  has  been  largely  used,  with 
asserted  good  results,  as  a  substitute  for  phosphorus.  According  to  the 
researches  of  Vigier,37  it  would  seem  that  the  phosphide  yields  its  phos- 
phorus within  the  economy,  probably  to  form  a  phosphuretted  hydrogen. 
He  found  that  it  killed  rabbits  more  quickly  than  did  a  corresponding 
dose  of  phosphorus,  and  that  both  symptoms  and  lesions  were  identical  in 
the  two  cases.  The  phosphide  should  be  given  in  pill  or  granule.  Dose, 
one-twentieth  to  one-twelfth  of  a  grain  (0.003-0.005  Gm.).  Seguin 
recommended  doses  of  one-sixth  to  one-fourth  of  a  grain  (0.016-0.01 
Gm.). 

ARSENI   TRIOXIDUM.     U.  S.     ARSENIC  TRIOXIDE. 

White  Arsenic,  Arsenic,  or  Arsenous  Acid,  as  first  prepared  by  sub- 
limation from  the  ores,  is  in  transparent  masses,  but  on  keeping  becomes 

*  In  the  manufacture  of  matches,  Phosphorus  sesquisulphide,  PiSs,  has  been  largely 
substituted  for  yellow  phosphorus,  and  is  believed  to  be  only  slightly  toxic.  For  a  study 
of  it,  see  C.  G.  Santesson  (V.  V.  N.  K.  I.  M.,  July,  1902). 


ALTERATIVES.  469 

milk  white  externally.  It  is  soluble  in  water,  has  a  vitreous  fracture,  is 
odorless,  of  a  faint  sweetish  taste,  and  volatilizes  without  fusion  "  at  a 
temperature  of  424.4°  F. "  When  it  is  put  upon  red-hot  iron  it  emits  a 
garlicky  odor,  owing  to  its  being  first  reduced  to  a  metallic  state  and 
then  volatilized. 

PHYSIOLOGICAL  ACTION. — Local  Action. —  When  in  concentrated 
form  arsenic  is  a  powerful  though  slowly  acting  escharotic,  and  even  when 
well  diluted  is  a  violent  irritant.  Although  a  violent  poison  to  all  forms 
of  life,  it  acts  proportionately  so  much  more  powerfully  upon  the  higher 
than  upon  the  lower  organisms  that  it  cannot  be  classed  among  the  prac- 
tical germicides.  Johannsohn  and  Schaefer  and  also  Boehm '  state  that 
it  exerts  no  influence  upon  non-organized  ferments,  either  vegetable  or 
animal,  such  as  amygdalin,  pepsin,  and  pancreatin. 

Absorption  and  Elimination. — Although  when  arsenic  is  taken  into 
the  stomach  in  lumps  it  may  be  absorbed  so  slowly  as  to  escape  in  part 
through  the  alimentary  canal,  when  it  is  taken  in  powder,  and  especially 
when  it  is  in  the  form  of  the  soluble  salt,  it  is  absorbed  with  rapidity. 

It  is  so  readily  taken  up  that  its  free  external  use  and  its  employment  as  an 
escharotic  are  accompanied  by  distinct  danger.  Six  cases  are  on  record  in  which 
severe  or  fatal  poisoning  has  been  produced  by  the  introduction  of  it  into  the 
vagina.* 

It  is  eliminated  chiefly  by  the  kidneys,  but  it  is  thrown  off  freely  when 
in  toxic  amount  by  all  the  excretory  glands  and  mucous  membranes, 
especially  by  those  of  the  gastro-intestinal  tract. 

M.  G.  Bouchet  and  Lewald  in  independent  researches  found  arsenic  in  notable 
quantities  in  the  milk  of  nursing  women,  f  Unterberger  has  detected  it  in  the  ali- 
mentary canal  of  animals  poisoned  by  injection  into  the  vein.  M.  Chatin  has  found 
it  in  the  serosity  of  a  blister,  Bergeron  and  Lemaitre  '2  in  the  sweat,  and  Taylor 3  in 
the  contents  of  the  stomach  of  a  child  poisoned  by  its  application  to  its  scalp. 

The  single  dose  escapes  rapidly  from  the  body,  elimination  being  usually  com- 
plete in  from  a  few  hours  to  three  or  four  days.  When  in  large  amount  it  may 
remain  long  in  the  body. 

Flandin  and  Danger*  failed,  three  days  after  the  last  dose,  to  detect  arsenic  in 
the  bodies  of  animals  to  which  fifteen  grains  had  been  given  daily  ;  and  in  a  child 
killed  in  two  days  by  an  arsenical  pigment,  none  of  the  metal  could  be  found  in 
the  body.5  In  the  great  majority  of  instances,  however,  there  is  no  trouble  in  find- 
ing arsenic  in  the  bodies  of  those  poisoned  by  it,  and  Steinhauser  6  reports  a  case  in 
which  it  was  detected  in  the  remnants  of  a  corpse  that  had  been  buried  for  twenty- 
two  years.  Further,  it  would  appear  that  the  failure  to  find  arsenic  has  often  de- 
pended upon  the  lack  of  delicacy  in  the  chemical  operations.  Using  the  chemical 
method  devised  by  Charles  R.  Sanger,  E.  S.  Wood7  has  been  able  to  detect  arsenic 
in  the  urine  ninety-three  days  after  the  taking  of  a  single  toxic  dose,  and  from  sixty 
to  eighty  days  after  mild  courses  of  Fowler's  solution. 

*  See  A.  Haberda  (  Wien.  Klin.  Wochenschr.,  1897,  x.  9,  201). 
t  See  American  Practitioner,  1887. 


470  GENERAL    REMEDIES. 

General  Action. — As  arsenic  is  never  used  in  medicine  for  an  acute 
effect,  the  chief  interest  to  the  therapeutist  centres  around  its  physiological 
action  when  given  in  small  doses  ;  yet  it  seems  necessary  here  to  take 
cognizance  of  the  physiological  action  of  large  amounts  of  the  poison.* 

Nervous  and  Muscular  System. — Arsenic  acts  powerfully  upon  the 
nerve-centres,  and  to  a  distinctly  less  extent  upon  the  nerve-trunks. 

In  the  frog  arsenic  acts  as  a  paralyzant  of  the  nerve-centres.  W.  Sklarck,2*  of 
Berlin,  states  that  the  small  dose  causes  in  the  frog  cessation  of  voluntary  movement, 
with  complete  loss  of  sensibility  to  chemical  and  mechanical  irritants  at  a  time  when 
the  animal  will  struggle  actively  to  recover  its  position  if  laid  upon  its  back.  Tying 
of  the  iliac  artery  had  no  effect  in  preserving  motion  or  sensibility  in  the  protected 
leg.  It  would  appear,  therefore,  that  the  cessation  of  voluntary  motion  was  due  to 
a  complete  paralysis  of  the  centres  of  common  sensation,  probably  up  to  the  per- 
ceptive centre  in  the  brain  ;  the  frog,  placed  upon  his  back,  being  induced  to 
struggle  into  the  normal  position  by  sensations  received  either  through  the  special 
senses  or  possibly  through  the  muscular  sense.  The  researches  of  Ringer  and  Mur- 
rell K  upon  frogs  yielded  very  different  results  from  those  just  described,  they 
found  that  the  symptoms  of  poisoning  came  on  only  after  the  lapse  of  some  hours, 
and  that  paralysis  of  voluntary  motion  preceded  that  of  sensation  and  reflex  action. 
Ringer  and  Murrell  suggest  that  these  differences  of  result  depend  upon  the  time 
of  year  at  which  the  frog  was  experimented  on. 

Circulation. — The  toxic  dose  of  arsenic  greatly  lessens  the  rate  and 
force  of  the  pulse-beat  and  markedly  lowers  the  blood-pressure.  Sklarck 
found  that  in  the  isolated  frog's  heart  arsenic  produces  slowness  and  fee- 
bleness of  pulsation,  ending  in  a  diastolic  arrest,  after  which  immediate 
galvanic  or  mechanical  irritation  caused  imperfect  systolic  movements.  It 
would  appear,  therefore,  that  the  toxic  dose  of  arsenic  is  a  direct  cardiac 
depressant ;  but  as  both  Cunza  and  Unterberger 26  have  found  that  in  ar- 
senical poisoning  the  heart  persists  in  its  movements  after  the  cessation 
of  respiration,  it  is  evident  that  arsenic  is  more  powerful  as  a  respiratory 
than  as  a  circulatory  poison.  Further,  as  demonstrated  by  Unterberger, 
the  lowering  of  the  arterial  pressure  in  arsenical  poisoning  is  very  largely 
due  to  a  vaso-motor  paralysis. 

Thus,  Unterberger  found  that  in  an  animal  under  the  influence  of  the  poison 
neither  galvanization  of  a  sensory  nerve  nor  of  the  vaso-motor  centre  in  the  upper 
cord  had  any  influence  upon  the  force  of  the  blood-current.  Galvanization  of  the 
splanchnics  had  no  effect  upon  the  arterial  pressure, — apparently  showing  that  the 
vaso-motor  palsy  was  peripheral ;  but  Unterberger  found,  to  his  astonishment,  that 
stimulation  of  the  cervical  sympathetics  had  the  usual  effect  upon  the  vessels  of  the 
rabbit's  ear.  Supposing  these  observations  to  be  correct,  there  are  only  two  seem- 

*  The  theory  of  Binz  and  Schulz,  that  arsenous  acid  acts  by  taking  from  protoplasm 
oxygen,  so  as  to  be  converted  into  arsenic  acid,  and  afterwards  yields  this  oxygen  to 
oxidize  the  protoplasm,  and  then  repeats  the  process,  seems  to  be  so  illy  supported  that 
in  regard  to  it  the  reader  is  simply  referred  to  Arch.f.  Exper.  Path.  u.  Pharm.,  xi.,  xiv., 
xxxvi.,  xli.  ;  also  Brit.  Med.  Journ.,  1882,  ii.  1135.  Dogiel's  theory,  that  arsenic  unites 
chemically  with  the  albuminous  principle,  is  more  probable.  (See  Trans.  International 
Congress,  1884,  i.,  134.) 


ALTERATIVES.  471 

ingly  possible  methods  of  reconciling  them  :  either  the  drug  acts  upon  the  peripheral 
vaso-motor  nerves  in  the  abdomen  and  not  upon  the  same  nerves  in  the  neck,  or  else 
there  is  during  arsenical  poisoning  such  depression  of  the  power  of  the  cardiac 
muscle  that  narrowing  of  the  blood-path  does  not  have  the  usual  effect.  Unterber- 
ger  found  that  compression  of  the  abdominal  aorta  was  followed  by  a  great  rise  of 
pressure,  and  therefore  he  believes  that  the  heart  in  arsenical  poisoning  has  not  lost 
its  power.  Some  complicated  transfusion  experiments  which  he  made  indicated 
differently  ;  so  that  while  his  proposition  that  arsenic  paralyzes  the  peripheral  vaso- 
motor  nerves  of  the  abdomen  and  not  those  of  the  head  may  be  considered  proba- 
ble, it  certainly  is  not  proved.  It  would  be  a  very  easy  matter  to  decide  the  ques- 
tion by  dividing  the  splanchnic  nerves  in  a  poisoned  animal :  if  the  reduction  of  the 
arterial  pressure  be  really  due  to  an  abdominal  vaso-motor  paresis,  section  of  the 
splanchnic  should  have  no  effect  on  it. 

Tissue- Change. — Schmidt  and  Stiirzwage  believe  that  arsenic  mark- 
edly influences  tissue- change,  because  they  found  in  rabbits  a  decided 
diminution  in  the  excretion  of  carbonic  acid  and  of  urea  during  the  use 
of  minute  doses  of  the  poison.  Fokker,27  however,  was  unable  to  per- 
ceive in  three  experiments  that  daily  doses  of  from  .15  to  .075  grain  of 
arsenic  to  a  dog  had  any  effect  upon  the  elimination  of  urea,  and  Kos- 
sell  and  Gaethgens,*8  in  two  experiments,  have  noted  a  very  decided 
increase  of  the  elimination  of  urea  produced  by  toxic  doses  of  arsenic  in 
the  dog.  The  experiments  of  Chittenden  and  Cummins  w  are  in  accord 
with  the  early  results  of  Stiirzwage,  as  they  found  that  in  the  case  of 
rabbits  arsenous  acid  has  a  tendency  to  diminish  the  elimination  of  car- 
bonic acid.  The  evidence  which  we  have  at  present  is  not  sufficient  to 
warrant  a  positive  opinion,  but  it  indicates  that  small  doses  of  arsenic  check 
tissue-change  and  decrease  nitrogenous  elimination,  while  large  toxic  doses 
have  the  opposite  effect. 

Blood. — As  arsenic  is  frequently  used  in  various  forms  of  anasmia  much 
interest  is  attached  to  its  effect  upon  the  formation  of  blood-corpuscles. 
Stockman  and  Charteris  3~  have  found  that  repeated  small  doses  of 
arsenic  cause  an  increase  in  the  formation  of  the  leucoblastic  cells  of  the 
bone  marrow,  with  consequent  stimulation  of  the  formation  of  white  blood- 
corpuscles,  but  without  marked  change  in  the  number  of  red  cells. 
Larger  doses  produced  a  hyaline  degeneration  of  the  bone  marrow  with 
a  decrease  in  the  number  of  both  white  and  red  cells. 

Skin. — The  changes  in  chronic  arsenical-poisoning,  especially  as  shown 
in  the  epidemic  which  occurred  in  Manchester,  in  1900,  as  the  result  of 
contaminated  beer,  bear  out  the  conclusions  of  clinical  experience,  that 
arsenic  has  a  marked  effect  upon  the  nutrition  of  the  skin.  According 
to  Brook,*8  the  most  characteristic  changes  in  the  skin  in  this  epidemic 
were  the  deposit  of  pigment  and  stimulation  in  the  growth  of  the  epithe- 
lium, similar  changes  occurring  also  in  the  modified  dermal  tissues,  such 
as  the  finger-nails. 

Action  of  Small  Doses. — Minute  quantities  of  arsenic  may  be  given 
for  a  long  time  without  perceptible  effect.  When  the  dose  is  increased, 
active  manifestations  of  gastro-intestinal  irritation  may  appear,  such  as 


472  GENERAL  REMEDIES. 

loss  of  appetite,  nausea,  abdominal  pain  or  uneasiness,  diarrhoea,  and 
perhaps  sympathetic  headache.  By  the  use  of  frequent  small  doses 
these  symptoms  may  generally  be  avoided,  and  what  may  be  termed 
the  constitutional  action  of  arsenic  be  obtained.  The  earliest  sign  of  this 
is  generally  a  puffiness  about  the  eyes,  at  first  visible  only  in  the  early 
morning,  but  soon  increasing  into  decided  oedema,  which  after  a  time 
may  lose  its  local  character  and  general  anasarca  develop.  This  ana- 
sarca,  as  was,  we  believe,  first  pointed  out  by  S.  Weir  Mitchell,30  may  or 
may  not  be  preceded  or  accompanied  by  the  presence  of  albumin  and  of 
tube-casts  in  the  urine.  Beyond  the  production  of  the  symptoms  spoken 
of,  arsenic  should  never  be  pushed  in  medicine. 

THERAPEUTICS. — When  arsenic  is  administered  in  small  repeated  doses, 
it  may  act  as  a  stomachic,  by  slightly  irritating  the  stomach  and  thereby 
provoking  an  appetite  ;  and  in  certain  cachexias  it  increases  the  muscular 
strength  and  the  general  vigor.  The  history  of  arsenic-eating  indicates 
that  the  drug  has  some  positive  tonic  influence  over  nutrition;  and  although 
the  increase  of  strength  and  of  blood  caused  by  its  use  in  cachexias  may 
be  due  to  some  indirect  action  of  the  drug, — for  example,  to  a  removal  or 
overcoming  of  the  morbific  agent  of  the  disease,  and  a  consequent  allow- 
ing of  the  recuperative  powers  of  the  system  so  assert  themselves, — there 
is  much  reason  for  believing  that  the  drug  does  act  as  a  direct  stimulant  to 
nutrition.  All  that  we  know  of  the  effect  of  arsenic  upon  the  system 
throws  only  enough  light  on  its  therapeutic  action  to  enable  us  to  class  it 
as  an  alterative, — a  modifier  and  often  an  improver  of  nutrition. 

After  very  much  discussion*  it  seems  to  be  established  that  many  of  the  Sty- 
rian  peasants  use  arsenic  habitually  in  large  quantities  ;  the  young  girls  to  beautify 
their  complexions  and  enhance  their  charms  ;  the  men  with  the  belief  that  it  will 
increase  their  "wind,"  endurance,  and  sexual  powers.  The  best  authorities  state 
that  the  arsenic-eating  is  practised  chiefly  in  the  northern  and  northwestern  parts  of 
Styria  :  that  the  white  arsenic  is  preferred,  the  yellow  commercial  article  being 
sometimes  taken  ;  the  native  red  arsenic,  or  orpiment,  very  rarely  ;  and  that  the 
commencing  dose  is  about  0.22  grain,  which  is  very  slowly  increased  to  0.62 
grain  avoirdupois. f 

Among  the  diseases  which  clinical  experience  demonstrates  are  espe- 
cially benefited  by  the  use  of  arsenic  is  chronic  malaria.  No  one  would 
at  present  think  of  employing  the  drug  in  acute  remittent  fever,  or  even 
in  acute  intermittent,  unless  under  very  peculiar  circumstances.  It  is 
in  those  cases  which  have  resisted  quinine,  in  which  the  paroxysms  have 
become  irr.egular,  returning  at  long  intervals,  and  in  which  the  anaemia 
and  the  general  nutritive  disturbance  are  even  more  prominent  than  the 

*SeeVogt  (Lehrbuch  der  Pharmacodynamik,  Aufl.  iii.  i.),  Charles  Heisch  (Pharm. 
Journ.  Trans.,  1859  and  1860,  i.  556;  British  and  Foreign  Med.-Chir.  Review,  xxix.  144), 
and  C.  Maclagan  (Edinb.  Med.  Journ.,  1864,  203;  Edinb.  Med.  and  Surg.  Journ.,  1871, 
xvi.  569). 

t  Maclagan  says  that  in  one  case  of  suspected  poisoning  in  Styria  the  prisoner  was 
acquitted  on  the  ground  that  the  deceased  was  an  arsenic-eater.  (See  also  Wiener  Klin. 
Wochensch.,  1812,  v.). 


ALTERATIVES.  473 

febrile  disorder,  that  arsenic  is  especially  valuable.  In  these  cases  it 
should  be  administered  with  sufficient  boldness,  very  generally  in  con- 
junction with  iron.  George  B.  Wood  recommended  that  the  first  doses 
should  be  as  large  as  the  system  will  endure,  so  as  to  make  a  decided 
impression  at  once.  When  the  ague  paroxysms  are  frequent  it  is  per- 
haps well  to  employ  this  plan  ;  but  when  it  is  the  cachexia  rather  than 
the  active  disorder  that  is  to  be  combated,  it  is  preferable  to  commence 
with  small  doses  and  to  increase  them  until  some  constitutional  symptom 
is  produced.  In  ordinary  intermittent,  after  the  paroxysms  have  been 
broken  up  by  quinine,  it  is  very  well  to  place  the  patient  upon  a  prepara- 
tion of  arsenic  and  iron,  as  a  prophylactic  against  their  return.  When, 
in  ordinary  intermittent  fever,  for  any  cause  quinine  cannot  be  admin- 
istered, arsenic  may  be  employed.  In  these  cases,  as  already  intimated, 
the  first  doses  should  be  large,  so  as  to  make  an  immediate  impression; 
from  five  to  ten  minims  of  Fowler's  solution,  properly  diluted,  maybe 
given  every  two  or  three  hours  until  some  decided  symptom  is  produced. 
When  the  stomach  refuses  the  remedy,  it  has  been  recommended  by  Boudin 
to  give  it  by  the  rectum,  which  he  affirms  will  often  bear  even  a  grain  of 
the  acid.  Not  more  than  a  third  of  this  amount  should,  however,  be 
used  as  a  commencing  dose.  In  malarial  intermittent  neuralgia,  arsenic 
may  be  employed  as  a  very  useful  adjuvant  to  the  antiperiodic  alkaloids. 
K.  M.  Downie 31  calls  attention  to  the  value  of  arsenic  as  a  prophylactic 
against  malaria.  His  trials  were  not  numerous  enough  to  be  conclusive, 
but  so  far  as  they  go  they  indicate  that  arsenic  is  even  superior  to 
quinine. 

It  is  alleged  that  arsenic  injected  directly  into  the  growth  is  an  effec- 
tive remedy  in  lymphatic  tumors,  especially  in  the  affection  known  as 
malignant  lymphoma* 

In  various  skin  diseases  arsenic  is  a  valuable  remedy.  According  to 
Duhring  it  affects  the  epidermis  generally  by  its  influence  upon  nutrition. 
It  is  more  commonly  useful  in  those  skin  diseases  involving  the  superficial 
strata  of  the  integument.  As  it  is  a  stimulant  it  should  ordinarily  not  be 
employed  in  the  acute  inflammatory  stages  of  skin  disease,  when  there  is 
burning,  itching,  and  rapid  cell  change.  Its  greatest  use  in  skin  diseases 
is  in  the  chronic  conditions,  as  in  psoriasis  and  in  eczema,  especially  of 
the  chronic  squamous  and  papular  varieties,  and  where  the  disease  is 
superficially  seated. 

Pemphigus  is  generally  favorably  influenced  and  often  relieved  or 
cured  by  its  use.  It  should  be  prescribed  cautiously  but  fearlessly,  large 
doses  usually  being  required.  It  is  the  most  reliable  remedy  for  this 
disease.  In  lichen  it  is  usually  employed  with  great  advantage,  especially 
in  lichen  planus,  in  the  rare  lichen  ruber  of  Hebra,  and  in  allied  diseases. 
Occasionally  it  may  be  given  with  benefit  in  chronic  urticaria. 

*  See  Wien.  Med.  Wochenschrifl,  1871 ;  Archiv  f.  Klin.  Chir.,  xviii. ;  Strieker's 
Jahrb.,  1877. 


474  GENERAL  REMEDIES. 

It  may  prove  of  value  in  certain  cases  of  acne  and  comedo,  especially 
in  chronic  small  papular  acne,  in  neurotic  cases.  In  certain  glandular 
hypersecretory  diseases,  as  seborrhcea  and  hyperidrosis  of  neurotic  origin, 
it  is  also  useful.  Before  prescribing  it  the  digestive  tract  should  be  care- 
fully looked  into,  and  if  disordered  in  the  slightest  degree  should  first  be 
rectified.  This  observation  holds  good  for  its  use  in  all  diseases  of  the 
skin.  In  morphoza,  alopecia  areata,  and  other  atrophic  diseases  it  is  also 
sometimes  of  value.  If  improvement  follows  its  use  it  is  usually  best  to 
allow  the  patient  to  continue  with  the  treatment  for  some  time  after  all 
symptoms  of  the  disease  have  disappeared. 

Arsenic  is  a  very  valuable  remedy  in  the  treatment  of  chronic  bron- 
chitis, and  is  often  of  the  greatest  service  not  only  in  chronic  pneumonia, 
or  so-called  fibroid  phthisis,  but  even  in  true  tubercular  phthisis  when  the 
course  is  very  slow  and  chronic.  In  asthma  it  may  be  given  internally 
and  also  used  locally.  (See  EXPECTORANTS.  ) 

In  certain  nervous  diseases  arsenic  acts  very  favorably,  in  some  un- 
known way.  In  chorea  it  has  acquired  a  deserved  reputation.  In  this 
affection  iron  and  other  tonics  are  generally  indicated  and  may  be  given 
consentaneously  with  the  arsenic.  It  is  best,  however,  to  administer  the 
latter  separately,  as  the  dose  must  be  steadily  increased  until  oedema  or 
other  manifestations  betray  a  decided  action.  Arsenic  has  from  time  to 
time  been  strongly  recommended  in  whooping-cough,  non-malarial  neu- 
ralgia, and  simple  gastralgia,  or  gastric  neuralgia, 

Arsenic  is  of  value  in  those  forms  of  chronic  rheumatism  in  which 
potassium  iodide  is  commonly  employed.  It  is  often  advantageous  to 
alternate,  administering  one  of  these  alteratives  for  three  or  four  weeks, 
and  then  the  other  for  the  same  length  of  time.  In  rheumatic  gout,  or 
rheumatoid  arthritis,  it  has  been  highly  extolled. 

TOXICOLOGY. — When  a  single  dose  of  arsenic  of  just  sufficient  size  to 
be  felt  is  ingested,  colicky  pains,  diarrhcea,  and  perhaps  nausea  result. 
After  a  very  large  toxic  dose,  in  from  one-quarter  to  three-quarters  of  an 
hour  an  intense  burning  pain  is  felt  in  the  oesophagus  and  stomach, 
soon  spreading  to  the  whole  belly,  and  often  accompanied  by  a  sense  of 
constriction  at  the  throat  and  an  acrid,  metallic  taste.  In  a  very  short 
time  violent  vomiting  and  purging  come  on.  The  matters  rejected  are  at 
first  mucous,  and  variously  colored  by  the  contents  of  the  primae  viae  ;  but 
they  soon  become  bilious,  often  yellowish  or  greenish,  and  finally  serous, 
with  mucoid  flakes  and  a  greater  or  less  amount  of  blood.  As  the  case 
progresses  the  symptoms  mentioned  increase  in  intensity,  and  to  them 
are  soon  added  others  of  different  nature.  The  thirst  is  excessive  ;  the 
urine  is  suppressed  ;  the  extremities  are  icy  cold  ;  the  pulse  is  small, 
feeble,  and  frequent ;  the  rapid  and  labored  respiration  is  very  much 
embarrassed  and  painful  from  the  abdominal  tenderness  ;  the  surface  is 
dark  and  cyanosed  ;  violent  cramps  add  their  torture  ;  exhaustion  deepens 
into  collapse  ;  convulsions  or  coma  ensue,  and  death  occurs  in  from  five 
to  twenty  hours. 


ALTERATIVES.  475 

In  another  set  of  cases,  when  the  dose  has  been  smaller,  or  the  sub- 
ject less  susceptible,  the  termination  is  not  reached  so  soon.  After  symp- 
toms, similar  to  but  less  violent  than  those  just  described,  have  lasted  from 
a  few  hours  to  one  or  two  days,  a  remission  occurs  ;  the  purging  and 
vomiting  grow  less  frequent,  or  perhaps  intermit ;  even  the  abdominal 
tenderness  may  in  great  measure  disappear  ;  but  the  persistent  thirst, 
cold  extremities,  and  albuminous  urine  show  that  the  danger  is  not 
past,  and  after  a  time  the  case  puts  on  a  more  alarming  aspect.  Fever 
develops,  the  tongue  becomes  dry  and  red,  the  belly  very  tumid,  the 
abdominal  pain  more  severe,  dyspnoea  and  cyanosis  occur,  the  face  is 
swollen,  nervous  symptoms,  tremblings,  cramps,  and  convulsions  appear, 
and  finally  an  icy  coldness  pervades  the  frame,  and  death  occurs  in  from 
two  to  six  days.  The  mind  is  generally  clear  to  the  last.  An  eruption 
very  frequently  appears,  sometimes  as  early  as  the  second  day,  sometimes 
not  until  the  fifth.  Its  character  is  various  :  thus,  it  may  be  petechial, 
urticaria-like,  papular,  vesicular,  or  pustular.* 

Such  are  the  ordinary  phenomena  of  acute  arsenical-poisoning  ;  but 
anomalous  cases  are  not  very  rare.  Immediate  profound  collapse,  with- 
out abdominal  pain,  is  said  to  have  been  the  chief  manifestation  in  some 
cases.  We  have  seen  heavy  sleep  as  the  most  marked  symptom,  the 
sleep,  however,  being  interrupted  at  intervals  by  wild  outcries  and  writh- 
ings,  evidently  the  outcome  of  abdominal  pain,  although  no  statement 
could  be  obtained  from  the  patient.  Again,  serous  purging  may  be  the 
chief  symptom,  and  arsenical-poisoning  has  been  mistaken  for  cholera, 
not  only  during  life,  but  also  on  the  post-mortem  table,  f 

When  arsenical-poisoning  is  not  fatal  the  convalescence  is  apt  to  be 
slow  and  interrupted  by  various  disorders.  Prominent  among  these  are 
affections  of  the  alimentary  canal,  due  to  the  structural  changes  produced 
by  the  poison.  Nervous  symptoms  are  common,  and  may  affect  the 
motor  or  sensory  sphere  separately  or  together.  In  some  cases  they 
have  developed  very  suddenly.8  We  have  seen  anaesthesia  of  the  feet  as 
the  only  symptom  ;  motor  paralysis  may  exist  alone,  but  it  is  usually  ac- 
companied by  anaesthesia,  hyperaesthesia,  loss  of  temperature-sense,  great 
feeling  of  coldness,  or  other  disorder  of  sensation,  and  not  rarely  exces- 
sive pain,  which  may  be  aching  or  lancinating.  Occasionally  there  are 
severe  cramps.  Normal  sensibility  is  usually  regained  before  normal 
motility.  Of  one  hundred  cases  of  arsenical  paralysis  collected  by 
Imbert-Gourbeyre,9  in  more  than  half  all  the  extremities  were  affected  ; 
about  one-fourth  were  paraplegic  ;  in  the  remainder  there  was  hemiplegia 
or  local  palsy.  Most  frequently  the  paralysis  was  not  pronounced  above 
the  elbow  or  knee.  The  lamed  muscles  are  usually  sensitive  to  pressure  J 

*  See  Imbert-Gourbeyre  (Moniteur  des  Hopit.,  1857),  also  A.  Huber  (Zeitschr.  Klin. 
Med.,  1888). 

t  See  Virchow's  Archiv,  1870,  1. 

t  Consult  C.  Gerhard  (Sitzungsb.  Physik.  Med.  Gesellsch.  Wiirzburg,  April,  1882), 
Renner  (Ueber  ein  Fall  von  chron.  Arsenvergift.,  Wurzburg,  1876),  W.  P.  Mclntosh 


476  GENERAL  REMEDIES. 

and  undergo  rapid  atrophy,  losing  very  early  their  electro-muscular  con- 
tractility, or  presenting  the  "  reactions  of  degeneration."  The  tendency 
towards  more  or  less  complete  recovery  is  remarkable.  We  have  seen 
recovery  when  the  muscular  remnants  on  the  wasted  limbs  had  for  many 
months  been  unable  to  respond  to  any  form  of  electric  current ;  and 
out  of  Imbert-Gourbeyre's  one  hundred  cases  all  got  well  except  three. 

N.  Popoff I0  found,  in  dogs  killed  in  a  few  hours  by  a  dose  of  arsenic,  the  spinal 
cord  inflamed;  after  slower  poisoning  there  were  masses  of  "exudate"  in  the 
neighborhood  of  the  blood-vessels,  and  in  very  protracted  cases  the  walls  of  the 
spinal  arterioles  were  found  to  be  thickened  and  the  large  cells  of  the  gray  matter 
profoundly  altered.  The  protoplasm  first  became  opaque  and  granular  ;  the  nuclei 
L,:L\V  fainter  and  fainter,  and  disappeared  ;  vacuoles  appeared,  and  encroached 
more  and  more  on  the  shrunken  body  of  the  cell,  which  finally  melted  down.  In 
the  elaborate  experiments,  however,  of  C.  Alexander11  upon  rabbits,  the  spinal  cord 
was  found  to  be  healthy,  but  the  nerve-trunks  were  in  a  condition  of  degenerative 
atrophy,  and  the  muscles  themselves  had  undergone  changes  which  were  believed 
to  be  the  result  of  coagulation-necrosis. 

That  arsenic  is  capable,  in  man,  of  producing  a  myelitis  especially 
affecting  the  multipolar  cells  of  the  cord  is  shown  by  the  autopsy  reported 
by  Erlicki  and  Rybalkin,12  in  which  case  there  was  no  tenderness  of  the 
nerve-trunks.  There  appear  to  be,  therefore,  two  forms  of  arsenical 
paralysis, — one  due  to  myelitic  change,  the  other  to  a  wide-spread  multiple 
neuritis, — the  diagnosis  between  the  two  being  made  by  the  presence  or 
absence  of  nerve-tenderness.  It  is  very  probable  that  in  some  cases  both 
lesions  are  present.*  In  some  of  these  cases  trophic  changes  are  pro- 
nounced :  thus,  we  have  seen  a  growth  of  hair  several  inches  long  cover 
the  wasted  limbs.  If  in  any  case  of  arsenical  paralysis  there  were  no 
sensory  disturbance,  the  probabilities  would  be  very  strong  that  the  lesion 
was  a  toxic  poliomyelitis. 

We  know  of  no  general  studies  upon  the  blood  of  human  beings 
poisoned  with  arsenic,  f 

S.  Betteman12  has  shown  that  in  the  rabbit  in  subacute  arsenical-poisoning 
there  is  a  marked  lessening  in  the  number  of  the  red  blood-corpuscles  and  in  the  per- 
centage of  haemoglobin,  without  any  distinct  change  in  the  general  percentage  of 
leucocytes,  although  the  lymphocytes  increase  and  the  eosinophile  cells  decrease. 
Late  in  the  poisoning  nucleated  red  blood-corpuscles  may  be  found  in  the  circu- 
lating blood. 

The  most  obvious  lesions  found  after  death  from  acute  arsenical-poi- 
soning are  those  of  severe  gastro-enteritis,  but  often  there  is  also  a  wide- 
spread granular  or  fatty  degeneration  of  the  tissues. 

(TV.  Y.  Med.  Record,  Feb.  1885,  145),  Seguin  (Journ.  Nerv.  and  Ment.  Diseases,  Oct. 
1882,  vii.  665),  and  C.  K.  Mills  (  Trans.  College  of  Physicians  of  Philadelphia,  3d  series, 
vi.  ;  Archives  de  Physiol.  Norm,  et  Path.,  1884,  iv.). 

*  See  also  Wiener  Klin.  Wochensch.,  1891,  iv. 

t  For  spectroscopic  study  of  the  effect  of  arsenic  upon  the  coloring  matter  of  the 
blood,  see  Centralblatt,  1868,  609.  It  is  interesting  here  to  note  that  arsenic,  antimony, 
phosphorus,  and  ammonia  act  very  similarly,  if  not  identically,  upon  the  blood- 


ALTERATIVES.  477 

The  gastric  mucous  membrane  is  usually  swollen,  maculated  with  patches 
of  a  deep  crimson  or  more  commonly  brownish-red  color,  and  is  often  softened 
and  covered  with  a  diphtheritic  exudation,  but  is  rarely  ulcerated.  Perforation  is 
exceedingly  uncommon.  The  mucous  membrane  of  the  upper  part  of  the  small 
intestine,  and  sometimes  of  the  whole  of  it,  is  in  a  condition  similar  to  that  of  the 
stomach.  In  some  cases  the  lesions  very  closely  resemble  those  of  cholera,  as 
was  first  pointed  out  by  Virchow.14  In  the  microscopic  examination  of  a  cadaver 
whose  bowels  were  filled  with  a  "rice-water"  fluid,  that  observer  found  in  the 
intestinal  contents  epithelial  flakes  and  the  fungus  described  by  Klebs  as  pecu- 
liar to,  and,  indeed,  the  cause  of,  cholera.  The  epithelial  cells  of  the  mucous  mem- 
brane were  choked  with  granules,  many  of  them  in  an  advanced  stage  of  fatty 
degeneration  ;  the  interstitial  tissue  was  full  of  large  round  granulated  cells  ;  the 
solitary  glands  and  Peyer's  patches  were  very  much  swollen.  These  facts  have 
been  confirmed  by  Hoffmann.15  The  gastro-intestinal  lesions  produced  by  arsenic 
are  not  due  solely  or  largely  to  its  immediate  local  effect,  since  they  occur  equally 
when  the  animal  is  killed  by  injection  of  the  poison  into  a  vein.  The  local  influence 
of  the  drug  is,  however,  probably  not  altogether  lost,  since  Unterberger  found  that 
a  larger  dose  was  required  to  kill  an  animal  by  venous  injection  than  by  exhibition 
by  the  mouth.  Curious  and  at  present  unexplainable  anomalies  occur  in  the  distri- 
bution of  the  gastro-intestinal  inflammation,  and  autopsies  have  been  reported  in 
which  the  stomach  has  altogether  escaped. 

M.  Karajau  16  reports  a  case  which  had  been  mistaken  during  life  for  acute 
atrophy  of  the  liver  ;  Fr.  Grohl  and  Fr.  Mosler 17  one  in  which  they  found  fatty  or 
granular  metamorphosis  of  the  glands  and  epithelium  of  the  stomach  or  intestines, 
of  the  cardiac  muscle,  of  the  diaphragm,  of  the  cortical  portions  of  the  kidney,  and, 
to  a  slight  extent,  of  some  of  the  voluntary  muscles  ;  I.  I.  Pinkham 1B  one  in  which 
the  liver,  kidneys,  and  epithelial  lining  of  the  peptic  glands  were  almost  destroyed  ; 
similar  lesions  have  also  been  reported  by  M.  V.  Cornil 19  and  by  F£r£ol.20 

As  was  first  pointed  out  by  Salkowsky21  when  animals  are  poisoned  by  a 
small  dose  of  arsenic,  so  as  to  live  from  three  to  six  days,  the  liver  *  becomes  much 
enlarged  and  very  fatty.  On  microscopical  examination,  the  cells  on  the  exterior 
of  each  acinus  are  natural ;  those  in  the  centre  in  the  most  advanced  stages  of  de- 
generation. The  kidneys  are  similarly  affected, — their  tubes  choked  up  with  fat- 
globules,  their  epithelium  almost  completely  destroyed.  The  muscles  of  the  heart 
and  diaphragm  are  also  compromised. 

In  frogs  poisoned  with  arsenic  the  epidermis  peels  off  from  the  derm,  as  was 
first  noted  by  Ringer  and  Murrell,  and  Emily  A.  Nunn  "  has  found  that  the  influence 
of  the  poison  is  first  manifested  in  the  under  portion  of  the  epidermis,  the  degener- 
ation progressing  from  the  derm  outward. 

In  some  cases  of  arsenical-poisoning  yellow  patches,  believed  to  be 
due  to  the  formation  of  arsenical  sulphides,  have  been  noted  on  the 
mucous  membrane  of  the  stomach  and  intestines.  Similar  yellow  de- 
posits were  found  by  Chunilal  Bose  '2Z  on  the  endocardium.  It  is  prob- 
able that  in  these  cases  the  sulphide  is  formed  after  death  by  the  aid  of 
putrefactive  gases. 


*  Salkowsky  also  noted  that  early  in  both  arsenical  and  antimonial  poisoning  the 
glycogenic  function  of  the  liver  is  abolished.  Podwyssotsky  finds  that  the  first  change 
produced  by  overwhelming  doses  of  arsenic  consists  in  the  formation  of  necrotic  foci  in 
the  liver  (St.  Petersburg  Med.  Wochensch.,  1888).  O.  Silberman  believes  that  during  life 
thrombi  form  in  various  portions  of  the  body  (Archil' f.  Path.  Anat.,  cxvii.).  For  further 
discussion  see  Ziegler  (Beitrage  Path.  Anat.,  ii.),  also  M.  Wolkow  (Archiv  f.  Path. 
Anat.  u.  Phys.,  1892,  cxxvii.). 


478  GENERAL  REMEDIES. 

The  symptoms  of  acute  arsenical-poisoning  resemble  so  closely  those 
of  cholera  nostras  that  without  the  knowledge  of  the  taking  of  the  poison, 
or  chemical  analysis  of  the  excretions,  a  positive  diagnosis  may  be  im- 
possible. The  abdominal  pain  is,  however,  usually  more  severe  than  in 
the  natural  disease. 

Death  usually  results  in  acute  arsenical-poisoning  in  from  eighteen 
hours  to  three  days  ;  but  Taylor  reports  a  case  in  which  it  occurred  with 
tetanic  symptoms  in  twenty  minutes,  and  life  has  been  protracted  until  the 
sixteenth  or  even  the  twentieth  day.  The  effects  of  the  arsenical  solu- 
tions, such  as  Fowler's,  are  more  rapid  and  severe  than  are  those  of  the 
solid  drug.  Tardieu  places  the  minimum  lethal  dose  at  from  ten  to 
fifteen  centigrammes  (1.54-2.31  grains.) 

W.  C.  Jackson  *3  records  a  case  of  recovery,  under  the  early  use  of  emetics, 
after  an  estimated  dose  of  two  ounces  had  been  taken  ;  and  E.  D.  Mackenzie14 
gives  an  account  of  a  man  who  swallowed  an  unknown  quantity  of  arsenic  in  lumps, 
and  received  no  treatment  for  sixteen  hours,  yet  recovered  after  passing  per  anum 
one  hundred  and  five  grains  of  arsenic  in  two  masses.  On  the  other  hand,  death 
has  resulted  from  the  use  of  very  small  amounts.  Taylor  asserts  that  the  smallest 
fatal  dose  hitherto  recorded  is  two  grains.  Lachese J5  affirms  that  six  milligrammes 
(0.09  grain)  will  produce  decided  but  not  serious  symptoms,  and  that  from  one  to 
three  centigrammes  (0.154-0.462  grain)  are  poisonous,  and  from  five  to  ten  centi- 
grammes (0.77-1.54  grain)  fatal.  The  escapes  from  death  after  the  ingestion  of 
large  amounts  of  arsenic  have,  without  doubt,  depended  upon  its  being,  as  in  the 
cases  above  narrated,  in  an  insoluble  form. 

Chronic  arsenical-poisoning  is  often  difficult  of  diagnosis  ;  the  symp- 
toms are  usually  both  local  and  constitutional.  When  the  poison  has 
entered  the  system  through  the  respiratory  tract  the  local  irritation  will 
be  shown  by  dryness  of  the  throat,  coughing,  and  other  evidences 
of  chronic  bronchitis  or  severe  laryngo-bronchial  catarrh.  When  the 
poison  has  entered  the  system  through  the  alimentary  tract,  loss  of  appe- 
tite, with  frequent  vomiting  and  violent  diarrhoea,  are  common.  The 
general  symptoms  consist  of  depression  of  spirits,  irritability,  insomnia, 
giddiness,  failure  of  memory,  sometimes  marked  mental  failure.  Accord- 
ing to  Reynolds,39  in  the  epidemic  which  was  caused  by  arsenical  beer, 
involvement  of  the  nerve-trunks  was  very  common.  There  was  in  these 
cases  marked  disturbances  of  sensation,  paraesthesia,  and  partial  anaes- 
thesia, although  complete  anaesthesia  was  rare.  There  may  be  muscular 
tremors  or  stiffness  ;  vertigo  or  other  disorders  of  equilibrium  are  some- 
times seen,  whilst  violent  neuralgic  pains,  with  numbness  of  the  extremi- 
ties, marked  tenderness  of  the  nerve-trunks,  and  other  results  of  periph- 
eral neuritis,  are  not  rare.  In  most  cases  of  chronic  arsenical-poisoning 
without  a  history  the  congeries  of  symptoms  is,  however,  sufficient  only 
to  arouse  suspicion  and  to  call  for  a  chemical  examination  of  the  urine. 
It  should  always  be  remembered  that  a  peripheral  neuritis  is  usually  due 
to  the  presence  of  some  poison,  and  that  a  group  of  wide-spread  atypical 
symptoms  not  characteristic  of  any  distinct  disease  is  usually  either  toxic 
or  diathetic. 


ALTERATIVES.  479 

Sometimes  in  acute,  more  frequently  in  chronic,  arsenical-poisoning, 
or  as  the  result  of  long-continued  medicinal  use  of  the  drug,  certain  dis- 
orders of  the  skin  appear.*  Of  these,  herpes  zoster  seems  to  be  the 
most  frequent  ;  it  probably  is  the  result  of  an  arsenical  neuritis.  Another 
common  skin  affection  is  erythromelalgia,  the  painful  red  swelling  of  the 
epiderm.  In  protracted  cases  there  is  frequently  thickening  of  the  horny 
tissue  in  the  palms  of  the  hands  and  soles  of  the  feet,  which  occasionally 
extends  up  the  limb.  The  formation  of  transverse  ridges  across  the  nails, 
the  result  of  the  hyperkeratosis  has  also  been  noted.  The  deposit  of 
pigment  in  the  skin  and  mucous  membranes  is  an  almost  constant  symp- 
tom,— while  there  have  been  noted  a  number  of  other  changes  in  the 
skin,  such  as  erythematous  and  desquamatous  eruptions,  urticaria  and 
subcutaneous  oedema,  vesicular  eruptions,  bullse,  papules,  pustules  and 
ulcers,  purpura,  shedding  of  the  hair  and  nails,  and  keratosis. 

In  artisans  who  work  in  copper  local  arsenical  poisoning  is  not  very 
rare.  Ulcers  about  the  roots  of  the  nails  are  generally  the  first  trouble 
in  these  cases,  but  after  a  time  eczematous  or  papular  eruptions  appear, 
and  even  subdermal  erysipelatous  inflammation  is  developed.  Very  com- 
monly to  these  local  symptoms  are  added,  after  a  time,  the  usual  phe- 
nomena of  chronic  arsenical  poisoning. 

In  the  arts,  preparations  of  arsenic  are  largely  used  as  pigments  ;  f 
and,  excepting  the  manufacturers  of  arsenical  compounds,  it  is  almost  ex- 
clusively those  who  are  accidentally  exposed  to  the  deleterious  influence 
of  these  pigments  that  suffer  from  chronic  arsenical  poisoning. 

The  poisonous  colors  are  of  various  hues,  and,  being  very  cheap,  and  remark- 
able for  their  purity  of  tone  and  their  permanence  under  exposure  to  light,  are 
much  used  by  paper-makers.  Scheele's  Green — copper  arsenite — contains  fifty-five 
per  cent.,  by  weight,  of  arsenous  acid  ;  and  Schweinfurt  Green — the  aceto-arsenite 
— fifty-eight  per  cent.  Paper  coated  with  them  has  been  largely  used  not  only  as 
hangings,  but  even  as  wrappings  for  confectionery  and  other  edibles.  The  arseni- 
cal dyes  are  not  all  green,  but  may  be  in  almost  any  hue  ;  they  are  largely  due  to  the 
use  of  arsenic  in  the  manufacture  of  magenta  and  other  aniline  colors.  E.  S. 
Wood,33  of  Harvard,  has  shown  that  in  different  parcels  of  the  same  goods  one 

*  See  Berlin.  Centralblatt,  1868;  Deutsche  Klinik,  1874 ;  Schmidt's  Jahrb.,  clxv. ; 
Deulsch.  Archiv  Klin.  Med.,  1899,  xliv. ;  Boston  Med.  and  Surg.Journ.,  cxviii.,  cxix., 
cxx.,  cxxi.,  cxxii. ;  Berlin  Thesis,  1892;  Ann.  Dermal,  el  Syph.,  iv. ;  Vierleljahr.  f. 
Derne.,  Wien,  1897,  xi. ;  Ann.  de  Dermatol.  el  de  Syph.,  1897,  viii.  4,  345;  Monals.  f. 
Prakt.  Dermatol.,  1897,  xxiv.  3,  137. 

t  For  an  excellent  report  upon  this  subject,  see  Report  of  the  Slate  Board  of  Health 
of  Massachusetts,  Jan.  1872,  where  it  is  stated  that  from  five  hundred  to  seven  hundred 
tons  of  arsenical  pigment  were  manufactured  in  1862  in  England  alone.  Fatal  chronic 
arsenical  poisoning  from  working  in  aniline  dyes  is  reported  in  Strieker's  Jahrb.,  1877, 
501.  F.  C.  Shattuck  (Med.  News,  1893,  Ixii.)  reports  a  number  of  cases  in  which  the 
symptoms  have  been  gastro-intestinal  irritation,  anaemia,  dermatitis,  redness  of  the  con- 
junctiva, puffiness  under  the  eyes,  headache,  irritation  of  the  upper  air-passages,  albumi- 
nuria  with  casts  and  blood,  and  peripheral  neuritis.  The  number  of  cases  of  chronic  ar- 
senical poisoning  detected  in  and  about  Boston,  contrasted  with  the  rest  of  the  world,  is 
something  remarkable,  and  is  scarcely  to  be  accounted  for  by  the  alleged  superior  acute- 
ness  of  the  Boston  physicians.  A  further  difficulty  of  the  subject  is  that  arsenic  has  been 
detected  in  the  urine  of  many  normal  Bostonians. 


480  GENERAL  REMEDIES. 

will  contain  arsenic  and  the  other  not,  because  the  aniline  dyes  are  sometimes  con- 
taminated with  arsenic  and  are  sometimes  free  from  it.  These  poisonous  colors  are 
by  no  means  confined  to  wall-paper.  Sweetmeats  have  been  colored  with  them  : 
pasteboard  boxes,  artificial  flowers,  tarlatan  dresses,  India  muslins,  cretonnes,  walls 
of  dwellings,  shelves  of  groceries,  toys  of  children,  and  various  other  articles  have 
been  made  the  vehicles  of  death,  so  that  hundreds  of  cases  of  poisoning  have 
resulted  from  the  use  of  these  pigments,  which  ought  to  be  banished  by  the  strictest 
laws.  In  most  cases  it  is  probably  the  minute  dust,  which  is  separated  mechanically 
and  diffused  through  the  room,  that  produces  the  fatal  result ;  but  poisoning  has 
occurred  when  the  arsenical  paper  was  covered  over  with  another  paper.  Hambers 
has  made  elaborate  chemical  researches  upon  the  air  of  these  apartments,  and  be- 
lieves that  he  has  demonstrated  that  some  arsenic  escapes  in  the  form  of  arsen- 
iuretted  hydrogen.  Not  rarely  the  poison  has  been  taken  directly  into  the  stomach, 
especially  by  children. 

TREATMENT — As  arsenic  in  large  doses  generally  induces  vomiting, 
it  is  rarely  necessary  in  poisoning  to  evacuate  the  stomach  by  artificial 
means.  If  free  emesis,  however,  have  not  occurred,  a  prompt  emetic, 
such  as  mustard  or  zinc  sulphate,  should  be  at  once  exhibited,  and  very 
generally  the  stomach  should  be  well  washed  out  by  large  draughts  of 
warm  water,  with  salt,  if  necessary  for  the  return  of  the  water.  With 
the  emetic,  or  sooner,  if  possible,  the  antidote  should  be  administered. 
The  most  certain  antidote  is  the  freshly  precipitated  ferric  hydrate,  which 
forms  with  arsenous  acid  a  very  insoluble  compound.  The  antidote  must 
be  freshly  prepared,  and  must  be  given  in  great  excess  ;  according  to  the 
experiments  of  T.  and  H.  Smith,  of  Edinburgh,  at  least  eight  grains  of 
the  iron  being  required  for  the  conversion  of  one  grain  of  the  arsenous 
acid. 

In  practice,  any  of  the  official  ferric  solutions — that  of  the  chloride  being  gen- 
erally preferred,  as  most  readily  procured — should  be  neutralized  by  sodium  car- 
bonate or  preferably  by  magnesia,  and  a  portion  of  the  precipitate  given  at  once, 
stirred  up  in  hot  water.  The  remainder  of  the  antidote,  having  been  hastily  washed 
by  emptying  it  on  to  a  piece  of  muslin  or  in  a  filter,  pouring  water  on  it  and  allowing 
it  to  drain,  should  be  administered  very -freely,  indeed  indefinitely,  as  it  is  en 
tirely  harmless.  H.  Kohler,36  of  Halle,  has  made  an  elaborate  series  of  chemical, 
physiological,  and  clinical  experiments  upon  the  comparative  antidotal  values  of  the 
saccharated  ferric  oxide  and  the  freshly  precipitated  ferric  hydrate.  His  results  indi- 
cate that  the  former  preparation  is  the  better  ;  but,  as  the  efficiency  of  the  hydrate 
has  been  so  frequently  proved  at  the  bedside,  further  testimony  is  desirable  before 
it  is  superseded,  especially  since  the  other  ferric  preparation  is  not  official  with  us, 
and  is  not  so  readily  prepared  on  the  spur  of  the  moment  as  is  its  fellow.  Dialyzed 
iron  has  been  used  with  very  good  results,  but  it  is  much  better  to  precipitate  it, 
just  before  administration,  with  a  small  amount  of  ammonia  or  other  alkali.  Mag- 
nesia, freshly  calcined  or  freshly  precipitated  from  a  solution  of  its  salts,  is  an  anti- 
dote of  some  avail  in  arsenical-poisoning,  but  is  decidedly  less  efficient  than  the 
iron  oxide. 

The  best  form  of  the  iron  antidote  is  probably  the  Ferric  Oxide  with 

*  Magnesia  (FE.RRI  OXIDUM  HYDRATUM  CUM  MAGNESIA,  U.  S. ),  Arsenical 

Antidote  of  the  German   Pharmacopoeia.      It  is  made   by  precipitating 

the  solution  of  ferric  sulphate  by  magnesia.      In  emergencies,  Monsel's 


ALTERATIVES.  481 

solution,  tincture  of  the  ferric  chloride  of  iron,  or  other  of  the  ferric 
preparations,  may  be  substituted  for  the  tersulphate. 

In  arsenical-poisoning  castor  oil  should  be  administered  for  the  pur- 
pose of  expelling  the  poison  from  the  bowels,  and  demulcent  drinks, 
opium,  stimulants,  dry  external  heat,  and  rubbing  should  be  employed  as 
called  for  by  the  symptoms.  When  there  is  a  tendency  to  suppression 
of  urine,  very  large  draughts  of  feebly  alkaline  water  should  be  given  as 
frequently  as  the  stomach  will  bear. 

The  chief  indications  in  chronic  arsenical-poisoning  are  to  remove  the 
patient  from  the  exposure  and  to  treat  symptoms  as  they  arise. 

Post-mortem  Imbibition. — Owing  to  the  extensive  use  of  embalming  with  liquids 
made  either  directly  from  arsenical  preparations  or  from  commercial  chemicals 
which  habitually  contain  arsenic  as  an  impurity,  it  is  becoming  extremely  difficult 
in  criminal  legal  practice,  as  it  occurs  in  the  United  States,  to  prove  death  from 
arsenical-poisoning.  Although  the  subject  is  somewhat  aside  from  the  main  motif 
of  the  present  volume,  its  importance  seems  to  require  a  brief  authoritative  con- 
sideration, the  details  of  which  may  be  found  in  recent  works  on  toxicology.  The 
old  belief  that  the  finding  of  arsenic  in  the  brain  or  organs  distant  from  the  abdo- 
men was  proof  that  the  poison  had  been  administered  during  life,  and  had  been 
scattered  by  absorption  *  and  not  by  imbibition,  is  absolutely  incorrect. 

The  qualitative  distribution  of  arsenic  in  the  body  is  of  very  little  service  in 
most  cases  in  determining  the  question  as  to  whether  the  poison  has  been  given 
before  or  after  death.  Arsenic  which  has  been  injected  into  the  thorax  or  into  the 
abdomen,  after  death,  may  be  found  subsequently  in  the  brain  and  other  distant  parts 
of  the  body.  More  respect  should  be  given  to  the  quantitative  distribution  of 
arsenic.  It  is  naturally  to  be  expected  that  more  arsenic  should  be  found  in  the 
parts  adjacent  to  the  points  of  injection  than  in  distant  portions  of  the  body  ;  and 
that  the  position  of  the  body,  through  the  force  of  gravity,  should  influence  the 
distribution  of  the  poison.  Thus,  if  the  corpse  has  lain  upon  the  back  more  arsenic 
should  be  found  in  the  back  tissues  than  in  those  in  the  upper  portions  of  the  body  ; 
if  on  the  left  side  more  poison  should  be  found  in  the  left  than  in  the  right  kidney. 
Nevertheless,  when  a  body  has  lain  for  many  weeks  after  post-mortem  arsenicaliza- 
tion  the  laws  of  diffusion  assert  themselves  against  the  law  of  gravity. 

To  be  of  any  value  whatever  the  quantitative  chemical  study  of  the  different 
organs  must  have  been  made  with  the  greatest  care  and  attention  to  details,  not 
only  chemical  but  also  physical.  The  whole  organ  must  have  been  used  or  reduced 
to  a  common  pulp,  a  portion  of  which  has  been  analyzed.  Moreover,  the  quantita- 
tive differences  must  be  most  pronounced,  or,  as  it  has  been  well  stated  by  Mann, 
"  must  be  absolute  not  relative  ;  the  left  kidney  must  contain  arsenic  and  the  right 
none  ;  it  is  not  enough  that  the  right  kidney  shall  contain  less  than  the  left ;  such  a 
difference  is  compatible  with  vital  absorption." 

Except  under  rare  circumstances,  as  when  the  body  has  been  buried  only  a  few 
days  after  embalming,  so  that  there  has  not  been  time  for  the  processes  of  imbib- 
ition to  carry  the  poison  throughout  the  organs,  the  expert  is  not  justified  in  assert- 
ing from  quantitative  evidence  that  the  poison  has  been  taken  during  life  :  the  im- 
perilling of  life  by  overconfidence  of  statement  is  not  a  rare  crime  in  American 
courts.  To-day  is  as  true  as  ever  that  at  present  the  dictum  of  Witthaus  and  of  Tor- 
sellini,  that  it  is  impossible  in  most  cases  to  distinguish  with  positiveness  by  chemical 

*  In  this  paragraph  the  word  "  absorption  "  is  used  technically  to  indicate  the  taking 
up  of  the  poison  during  life;  "  imbibition  "  to  indicate  the  passage  of  the  poison  from 
tissue  to  tissue  after  death. 

31 


482  GENERAL  REMEDIES. 

analysis  between  absorption  and  imbibition,  or,  in  other  words,  whether  the  poison 
has  been  put  into  the  body  before  or  after  death.* 

ADMINISTRATION. — The  beginning  dose  of  arsenic  is  one-thirtieth 
of  a  grain  (0.002  Gm. ),  which  should  be  given  in  pill  after  meals,  and 
be  slowly  increased  until  a  perceptible  influence,  or  the  desired  therapeu- 
tic effect,  is  obtained.  In  many  cases  {chorea,  lymphoma,  intermittent 
fevers,  etc. )  it  is  necessary  to  push  the  remedy  until  decided  evidences 
of  poisoning  are  secured  :  in  this  case  a  liquid  preparation  should  be 
selected.  The  following  are  the  official  preparations  of  arsenic  : 

LIQUOR  POTASSII  ARSENITIS.  U.  S. — Fowler1  s  Solution  (one  per 
cent. )  is  nearly  colorless  and  odorless,  with  a  faint  taste  of  the  compound 
spirit  of  lavender,  which  is  in  it.  Dose,  five  to  ten  drops  (0.3-0.6  C.c. ) 
in  a  wineglassful  of  water  after  meals,  to  be  increased  and  used  with  the 
same  precautions  as  arsenic. 

SODII  ARSENAS.  U.  S. — Sodium  Arsenate  occurs  in  transparent, 
slightly  efflorescent,  soluble  crystals,  and  is  solely  used  in  making  the 
LIQUOR  SODII  ARSENATIS,  U.  S.  Solution  of  Sodium  Arsenate  (about 
four  and  a  half  grains  to  one  fluidounce)  is  equivalent  to  Fowler's  Solution. 

LIQUOR  ACIDI  ARSENOSI.  U.  S. — Solution  of  Arsenious  Acid  is  in 
strength  and  therapeutic  use  equivalent  to  Fowler's  solution. 

ARSENI  IODIDUM.  U.  S. — Arsenic  Iodide. — This  is  an  orange-red, 
crystalline  solid,  wholly  soluble  in  water  and  entirely  volatilized  by  heat. 
It  has  been  used  as  an  alterative,  and  also  as  an  external  application  in 
lupus  and  chronic  tubercular  affections. 

CACODYLIC  ACID. — Cacodylic  acid  is  chemically  di-methyl-arsenic  acid.  Several 
of  its  salts  have  been  employed  in  medicine  as  substitutes  for  arsenic.  It  has 
been  claimed  for  these  preparations  that  they  are  much  less  poisonous  than  the 
ordinary  arsenical  preparations,  and  can  be  used  freely  without  danger  of  causing 
unpleasant  symptoms.  It  would  seem  that  their  low  degree  of  toxicity  depends 
upon  the  fact  that  the  arsenic  is  so  firmly  bound  up  in  the  composition  that  it  is  liber- 
ated in  the  body  only  in  very  small  quantities,  since  the  experiments  of  Heffter 1 
indicate  that  only  about  two  or  three  per  cent,  of  sodium  cacodylate  is  destroyed  in 
the  body  and  eliminated  as  arsenic.  It  is  therefore  probable,  as  claimed  by  Heffter, 
that  the  cacodylate  is  not  active  as  such  but  only  through  the  liberation  of  free 
arsenic.  This  view  is  also  held  by  Fraser,2  who  has  used  the  remedy  in  a  number 
of  cases  of  chorea,  eczema,  leukemia,  and  chlorosis  without  special  result.  The 
remedy  has  been  especially  lauded  by  Gautier,3  who  has  employed  it  in  various 
forms  of  tuberculosis  with  asserted  good  results.  Sodium  cacodylate  has  been 
used  as  a  substitute  for  arsenic  in  all  the  conditions  in  which  this  remedy  is  useful, 
in  doses  of  one-quarter  to  one  grain  (0.016-0.06  Gm.).  In  chlorosis  and  other 
forms  of  anaemia  the  cacodylate  of  iron  is  preferred,  and  may  be  given  in  the  same 
dose.  According  to  Gautier  it  is  always  preferable  to  give  the  remedy  subcutane- 
ously.  Under  these  circumstances  a  five  per  cent,  solution  may  be  employed,  of 
which  one  c.c.  (15  minims)  may  be  given  at  a  dose. 

*  American  readers  see  especially  Medical  Jurisprudence  and  Forensic  Medicine 
and  Toxicology,  by  Witthaus  and  Becker.  Also  Text-book  of  Legal  Medicine  and 
Toxicology,  by  Peterson  and  H  aines.  Also  Forensic  Medicine  and  Toxicology,  by 
Dixon  Mann. 


ALTERATIVES.  483 

ATOXYL.  Meta-arsenic-anilid. — This  is  a  white,  odorless  powder,  soluble  in 
twenty  per  cent,  of  hot  water,  and  containing  thirty-seven  and  six-tenths  per  cent, 
of  metallic  arsenic.  According  to  Blumenthal  it  is  forty  times  less  poisonous  than 
arsenic  acid,  but  as  its  physiological,  toxic,  and  remedial  properties  are  probably 
in  direct  proportion  to  the  amount  of  arsenic  eliminated  in  the  system,  it  does  not 
seem  probable  that  it  has  any  advantage  over  the  older  preparations  of  arsenic. 
It  is  claimed,  however,  to  lend  itself  especially  well  to  hypodermic  medication  ; 
according  to  Schild,  three  to  fifteen  minims  of  the  twenty  per  cent,  solution  may  be 
given  hypodermically  for  five  days,  subsequently  on  alternate  days.  Schild  believes 
that  it  is  especially  liable  to  act  upon  the  heart,  and  considers  cardiac  weakness  a 
centra-indication  to  its  use. 

HYDRARGYRUM— MERCURY.     U.  S. 

Local  Action. — The  local  effect  of  mercurial  preparations  varies  from 
complete  inertness  to  an  active  escharotic  influence,  so  that  each  prepa- 
ration must  in  this  regard  be  studied  by  itself. 

Absorption  and  Elimination. — All  preparations  of  mercury  yield  them- 
selves or  the  mercury  in  them  to  absorption,  and  after  absorption  to  elimi- 
nation. The  metal  has  been  found  in  the  blood,*  in  the  urine,  in  the 
serum  of  blisters,  in  the  saliva,  in  the  faeces,  in  the  pus  from  ulcers,  in  the 
seminal  fluid,  in  the  milk  of  nursing  women, — indeed,  in  every  conceivable 
secretion  and  in  every  tissue.  Heller  found  it  in  the  aborted  foetuses  of 
salivated  women,  and  Mayen9on  and  Bergeret  in  the  urine  of  a  baby  whose 
nurse  was  taking  calomel  ;'  and  each  of  these  observations  has  been  con- 
firmed by  Wellander. 

An  enormous  amount  of  work  has  been  done  to  determine  how 
rapidly  mercury  is  eliminated,  and  whether  when  given  internally  it  is  all 
thrown  out  of  the  system.  The  result  of  all  this  labor  seems  to  us  to 
prove  that  the  single  dose  of  mercury  does  not  remain  in  the  system, 
but  that  when  the  drug  is  administered  constantly  for  a  length  of  time 
elimination  does  not  keep  pace  with  absorption,  so  that  the  mercury  ac- 
cumulates in  the  tissues.  Moreover,  the  elimination  takes  place  irregu- 
larly and  intermittently,  for  reasons  that  at  present  cannot  be  made  out. 
Further,  there  does  not  appear  to  be  any  limit  of  time  during  which 
stored-up  mercury  may  remain  in  the  body  ;  indeed,  all  the  evidence 
points  to  the  possibility  of  mercury  being  deposited  in  the  tissues  in  such 
form  that  it  is  practically  inert  and  has  no  influence  upon  the  system  ; 
liable,  however,  under  certain  agencies,  to  be  set  free  and  to  exert  its 
power  upon  the  general  nutrition,  f 

*  Cantu,  Jourda,  Andouard,  Fourcroy  (quoted  by  Stille) ;  Gmelin  (Bull,  de  Therap., 
xiii.) ;  Byanon  (quoted  by  Mayencon  and  Bergeret);  Salkowsky  ( Virchow's  Archiv, 
xxxvii.  347);  Salkowsky  (loc.  cit.,  347);  Mayenfon  and  Bergeret  (Robin's  Journal 
de  T Anatomic,  1873) ;  Klinik  (Detroit.  Me d.  Jour n.,  May,  1877). 

t  The  rate  of  absorption  of  mercury  is  of  course  affected  by  the  choice  of  preparation 
and  by  the  method  of  administration.  Wellander  (Ann.  Dermatolog.,  vii.  413)  has  found 
mercury  in  the  urine  fourteen  hours  after  its  application  to  the  human  skin  and  one  hour 
after  its  subcutaneous  administration.  Mayencon  and  Bergeret  found  that  when  one 
centigramme  of  corrosive  sublimate  was  given  hypodermically  to  a  dog,  the  urine  for  the 
next  twenty-four  hours  contained  mercury,  afterwards  none.  When  a  centigramme  was 


484  GENERAL  REMEDIES. 

PHYSIOLOGICAL  ACTION. — When  a  mild,  unirritating  preparation  of 
mercury  is  introduced  into  the  system  so  as  to  produce  constitutional 
effects,  the  first  symptoms  of  its  action  are  to  be  looked  for  in  the  mouth. 
In  the  mildest  degree  these  symptoms  consist  of  a  slight  fetor  of  the 
breath,  and  some  soreness  of  the  teeth  when  knocked  forcibly  together 
or  struck  with  a  key.  Mercurial  fetor  of  the  breath  is  generally  the 
first  indication  that  the  drug  is  affecting  the  system,  and  is  sooner  or 
later  accompanied  by  a  disagreeable  metallic  taste.  If  the  use  of  the 
mercury  be  persisted  in  the  gums  become  swollen,  soft,  and  spongy, 
bleeding  on  very  slight  abrasion,  and  there  is  a  decided  increase  in  the 
secretion  of  saliva.  Beyond  this  point  the  therapeutist  is  never  justified 
in  carrying  the  use  of  the  drug..  If  it  be  done,  the  local  symptoms  in  the 
mouth  increase  in  severity,  the  tumefied  gums  become  inflamed,  very 
vascular,  and  marked  by  a  dark  red  line  at  the  junction  of  the  teeth  ;  the 
tongue  is  also  swollen,  sometimes  enormously,  protruding  from  the 

given  daily  for  ten  or  twelve  days,  the  urine  contained  mercury  for  four  or  five  days  after 
the  cessation  of  medication.  In  their  last  series  of  experiments,  rabbits  received  the  drug, 
and  were  killed  at  different  intervals :  in  half  an  hour  the  metal  could  be  found  in  all  the 
tissues,  the  liver  and  kidneys  containing  most  of  it ;  in  four  days,  or  even  in  a  shorter 
time,  mercury  given  in  a  single  dose  was  all  eliminated,  and  could  not  be  found  in  the 
tissues. 

The  evidence  in  favor  of  the  storing  up  of  mercury  in  the  system  is  overwhelming. 
In  1880  Vajda  and  Paschkis  ( Ueber  den  Einfluss  Quecksilbers,  Wien)  stated  that  they 
found  the  metal  in  the  urine  in  different  cases,  six  months,  one  year,  two  years,  and  even 
twelve  and  thirteen  years  after  the  mercurial  course.  Mayencon  and  Bergeret  found  that 
the  exhibition  of  potassium  iodide  forty-eight  hours  after  the  cessation  of  a  mercurial 
course,  when  the  urine  was  free  from  mercury,  would  bring  about  the  immediate  elimi- 
nation of  mercury.  Sigismund  has  detected  quicksilver  in  the  urine  of  patients  as  long  as 
thirteen  years  after  taking  the  medicine  ;  but  Schuster  (Zeitschr.f.  Klin.  Med.,  1884,  vii.) 
asserts  that  these  patients  were  habitues  of  a  room  in  which  inunctions  were  constantly 
being  made,  and  that  under  these  circumstances  there  is  sufficient  diffusion  of  the  mercury 
to  produce  a  very  sensible  effect  in  those  breathing  the  air.  Apparently,  however,  using  all 
precaution  and  having  the  patient  carefully  watched,  H.  Stein  (  Wiener  Klin.  Wochens., 
1890)  has  obtained  weighable  amounts  of  eliminated  quicksilver  from  the  urine  four  weeks 
after  its  inunction.  (See  also  Viertelj.  f.  Dermal,  u.  Syphilis,  1882;  Annales  de  Der- 
mal, et  Syphil.,  1882,  iii.).  Schuster  has  found  it  in  the  faeces  three  months  after  the  ces- 
sation of  a  mercurial  course  (  Viertelj.  f.  Dermal,  u.  Syphilis,  ix.  307) ;  indeed,  he  believes 
that  it  is  thrown  off  more  freely  and  constantly  by  the  intestines  than  by  the  kidneys. 
He  also  asserts  that  elimination  is  completed  six  months  after  the  cessation  of  an  ordinary 
mercurial  course  (Journ.  of  Cutan.  Med.,  i.  No.  12,  ii.  No.  9).  According  to  Gola  (A.  I. 
P.  T.,  1900,  viii.  203)  when  the  kidney  elimination  is  great  the  intestinal  output  is  small 
and  vice  versa.  In  an  elaborate  memoir  on  the  elimination  of  mercury,  Balzer  and 
Klumpke  (Revue  de  Medecine,  1888,  viii.)  state  that  extraordinary  exacerbations  and 
remissions  occur  in  the  elimination  during  treatment,  that  Michaelowsky  and  Souchow 
have  shown  that  the  effect  of  potassium  iodide  is  small,  but  that  Stepanow  has  proved 
that  the  hot-air  baths  increase  enormously  the  elimination.  It  appears  to  be  established 
that  in  these  cases  of  long  continuance  the  mercury  escapes  not  only  through  the  kidneys, 
but  is  also  excreted  by  the  salivary  glands  as  well  as  by  the  intestines,  and  hence  its  con- 
tinuing elimination  may  be  overlooked  by  the  chemist,  who  simply  studies  the  urine. 
(See  paper  by  Stein  and  Kronfeld,  Wiener  Med.  Wochen.,  1890.) 

Method  of  Preparing  Tissues  for  Microscopic  Detection  of  Mercury. — J.  Almkvist 
(S.  J.,  Bd.,  cclxxx.,  p.  177)  soaks  the  freshly  cut  pieces  for  eight  or  ten  hours  in  a  solution 
of  sulphuretted  hydrogen,  containing  four  per  cent,  of  nitric  acid,  producing  a  yellow 
precipitate  of  mercuric  sulphide  ;  subsequently  he  hardens  in  alcohol  or  other  fluid  not 
containing  iodine,  and  cuts. 


ALTERATIVES.  485 

mouth,  whose  closure  it  may  entirely  prevent  ;  the  teeth  are  loosened  in 
their  sockets  ;  the  saliva  is  enormously  increased  in  quantity  and  altered 
in  quality,  forming  great,  ropy,  viscid  masses,  which  pour  over  the  thick- 
ened lips  ;  the  parotid  glands,  and  even  the  submaxillary,  are  very  much 
enlarged  and  tender.  Severe  ptyalism  may  be  accompanied  by  marked 
fever,  and  nephritis  is  a  not  uncommon  occurrence.  Loss  of  the  teeth, 
extensive  ulceration  of  the  soft  parts,  and  even  necrosis  of  the  jaw-bones 
have  occurred,  and  death  from  exhaustion  resulted,  or  the  patient  strug- 
gled through  to  recovery,  seamed  and  disfigured  for  life.  In  these  cases 
passive  hemorrhages  often  recur  again  and  again,  and  may  contribute 
largely  to  a  fatal  result.  During  severe  ptyalism  emaciation  goes  on 
rapidly,  and  seems  to  especially  affect  imperfectly  organized  tissues,  so 
that  exudations  very  generally  rapidly  disappear.  The  disturbance  of 
nutrition  is  further  shown  in  some  cases  by  the  occurrence  of  ulcers  upon 
the  extremities.  The  blood  suffers  very  decidedly,  becoming  more  fluid 
and  watery  than  normal  and  having  its  power  of  coagulation  impaired. 
According  to  the  researches  of  Wright,  its  solid  constituents  are  notably 
diminished,  including  albumin,  fibrin,  and  the  red  corpuscles,  and  it  con- 
tains a  large  quantity  of  a  fetid,  fatty  material.  These  observations  of 
Wright  have  been  confirmed  upon  animals  by  Wilbouchewitch,1  and  by 
I.  Hughes  Bennett. 

Although  large  doses  of  mercury  lower  the  general  nutrition  and  de- 
stroy the  crasis  of  the  blood,  it  is  probable  that  when  given  in  very  minute 
doses  it  has  tonic  properties. 

In  1869  Liegeois2  asserted  that  the  subcutaneous  injection  of  very  minute  doses 
of  quicksilver  produces  in  healthy  men  an  increase  of  their  bodily  weight,  and  in 
1876,  in  two  experiments,  E.  L.  Keyes3  found  that  not  only  was  the  bodily  weight 
increased,  but,  as  determined  by  actual  count,  the  number  of  the  red  corpuscles 
was  decidedly  augmented.  '  Hermann  Schlesinger*  has  laboriously  experimented 
upon  rabbits  and  dogs.  All  other  conditions  being  similar,  those  rabbits  which 
received  the  mercury  increased  in  weight  a  little  more  than  did  those  to  which 
mercury  was  not  given,  but  the  augmentation  of  the  red  blood-disks  was  distinctly 
greater  in  the  mercurialized  animals.  With  dogs  the  results  were  more  decided, 
both  bodily  weight  and  blood-corpuscles  increasing  much  faster  in  the  animals  to 
which  mercury  was  given.  I.  Hughes  Bennett  had  previously  obtained  results 
similar  to  those  quoted,  and  Schlesinger  thinks  that  it  must  be  considered  proved 
that  very  minute  continuous  doses  of  mercurials  tend  in  the  normal  animal  or  man 
to  increase  distinctly  the  weight  of  the  body  and  the  richness  of  the  blood,  but  that 
it  is  scarcely  proper  to  call  them  tonic,  as  in  his  belief  they  act  by  hindering  oxi- 
dation and  restricting  waste,  and  not  by  aiding  in  reconstruction, — a  conclusion 
which  is  purely  theoretic  and  unproved.  In  some  cases  of  syphilitic  anaemia  the 
effect  of  mercury  in  increasing  the  number  of  red  blood-corpuscles  is  very  marked. 
This  effect  is,  however,  to  be  attributed  to  the  antisyphilitic  influence  of  the  remedy 
rather  than  to  any  specific  action  on  the  blood-making  organs.  (For  elaborate 
paper,  see  L.  Gaillard.8) 

The  ordinary  symptoms  of  mercurialization  have  been  sufficiently 
described,  but  there  are  on  record  various  anomalous  cases.  In  some 
instances  the  chief  symptoms  of  mercurialism  have  been  cutaneous. 


486  GENERAL  REMEDIES. 

The  usual  eruption  is  a  polymorphic  erythema,  resembling  more  or  less  that  of 
scarlet  fever.  In  rarer  cases  the  eruption  may  be  distinctly  erysipelatous,  with  sub- 
dermal  cedematous  swelling.  Sometimes  it  takes  the  form  of  urticaria,  or  even  of  a 
roseola  ;  a  very  severe  eczema,  becoming  finally  pustular,  has  in  some  cases  been  pro- 
duced, most  frequently  as  the  result  of  an  inunction  ;  whilst  mercurial  pemphigus  and 
purpura  have  both  been  recorded.  Usually  the  eruption  is  fugacious,  being  followed 
in  two  or  three  days  by  more  or  less  desquamation,  but  very  grave  cases  have  been 
recorded  in  which  there  has  been  a  universal  dermatitis,  with  great  swelling  of  the 
face  and  extremities,  excessive  desquamation,  followed  by  thickening  and  infiltra- 
tion of  the  subdermal  tissues,  excoriation,  violent  fever,  disturbance  of  the  respi- 
ration, and  death  ;  or,  if  the  patient  survive,  months  of  illness  (see  M.  A.  Morel- 
Lavalle"e.6 

Sometimes  the  influence  of  mercury  falls  almost  exclusively  upon  the 
nervous  system,  and  produces  a  peculiar  train  of  paralytic  phenomena. 

Nervous  mercurialism  occurs  chiefly  when  mercurial  vapors  find  entrance 
through  the  lungs,  and  is  most  frequently  seen  in  workers  in  the  metal.  It  is  gen- 
erally the  result  of  long  exposure  ;  but  that  it  may  be  produced  in  a  very  short  time 
is  proved  by  the  case,  related  by  Christison,  of  two  barometer-makers  who  slept  one 
night  in  a  room  containing  a  pot  of  mercury  upon  a  stove.  One  was  severely  sali- 
vated, the  other  was  affected  with  a  shaking  palsy  which  lasted  all  his  life.  Accord- 
ing to  Sigmond,7  the  attack  of  mercurial  palsy,  which  is  sometimes  sudden,  some- 
times gradual,  begins  with  unsteadiness  and  shaking  of  the  extremities  and  of  the 
muscles  of  the  face,  which  movements  interfere  with  walking,  speaking,  or  chewing  ; 
the  tremors  become  frequent,  nay,  almost  constant ;  ' '  every  action  is  performed  by 
starts."  If  the  exposure  be  continued,  sleeplessness,  loss  of  memory,  and  death 
terminate  the  scene.  A  peculiar  brownish  hue  of  the  whole  body,  and  dry  skin, 
generally  accompany  the  disease.  In  its  first  attack  it  may  be  mistaken  for  St. 
Virus's  dance ;  in  its  latter  stages,  for  delirium  tremens.  According  to  Noel 
Gue'neau  de  Mussy,8  these  two  forms  are  distinct  varieties  rather  than  different  stages 
of  mercurial  tremors.  In  the  latter  the  affection  simulates  paralysis  agitans  in  its 
shaking  movements  ;  in  the  former  the  motions  are  violent,  and  occur  independently 
of  the  will  of  the  patient,  even  when  he  is  lying  quietly  in  bed.  In  a  case  reported 
by  L.  Langer,9  the  electro-contractility  of  the  affected  muscles  was  much  heightened. 

Paralysis  from  chronic  mercurial  poisoning  is  said  to  be  not  a  rare  affection 
among  artisans  and  miners  who  are  in  their  daily  occupation  exposed  to  contact 
with  the  metal  or  its  fumes.  The  subject  has  been  thoroughly  discussed  by  M. 
M.  Letulle,10  to  whose  paper  the  reader  is  referred  for  a  collection  of  recorded 
cases  and  for  details.  In  a  case  reported  by  Sigmond,  symptoms  similar  to  those 
of  chronic  lead-poisoning,  including  wrist-drop,  followed  repeated  mercurial 
inunctions.  In  some  cases  mercurial  paralysis  takes  the  form  of  multiple  palsy,  or 
of  a  brachial  or  crural  monoplegia,  or  of  an  obscure  local  palsy,  as  in  a  case  re- 
ported by  Kiissmaul,  in  which  there  was  aphonia  from  paralysis  of  the  laryngeal 
muscles.  Almost  invariably  the  loss  of  motor  power  is  accompanied  by  an  anaes- 
thesia, which  may  be  wide-spread  or  may  be  in  isolated  islets,  or  may  take  the  form 
of  hemiansesthesia.  The  loss  of  sensation  is  very  rarely  absolute  ;  simple  loss  of 
the  thermic  sensibility  or  analgesia  may  exist  alone.  Partial  anosmia  or  amblyopia 
may  show  that  the  nerves  of  special  sensation  are  affected.  Neuralgic  pains  may 
be  the  permanent  result  of  a  mercurial  exposure,  and  epilepsy  and  even  insanity, 
most  frequently  of  the  melancholic  type,  are  stated  to  have  been  so  produced. 
According  to  Letulle,  trophic  changes  are  not  common,  the  paralyzed  muscles  not 
undergoing  atrophy,  and  retaining  their  normal  relations  to  the  galvanic  and  faradic 
currents.  When  the  thighs  are  affected  the  knee-jerk  may  entirely  disappear. 
Guinon  "  describes  violent  hysteria  following  upon  chronic  mercurial  intoxication. 


ALTERATIVES.  487 

In  some  cases  exposure  to  the  vapor  of  mercury,  or  even  its  persist- 
ent medicinal  use,  has  resulted  in  the  production  of  a  state  of  the  system 
somewhat  resembling  scurvy,  characterized  by  great  anaemia,  emaciation, 
and  general  loss  of  power,  with  loss  of  the  hair,  aching  pains  in  the  bones 
and  joints,  oedema,  fetid  breath,  diarrhoea,  and  generally  disordered 
secretions.  This  is  the  so-called  mercurial  cache xia* 

There  is  some  reason  for  believing  that  the  pancreas  is  especially 
affected  by  mercury.  Thus,  in  a  case  related  by  Copland,  a  woman  after 
excessive  salivation  experienced  deep-seated  epigastric  pain  and  heat, 
with  nausea,  thirst,  and  fever,  and  voided  thin  stools  containing  liquid 
resembling  salivary  fluid.  At  the  post-mortem  the  pancreas  was  found 
weighing  four  ounces,  red,  congested,  and  with  its  duct  dilated.  In  re- 
gard to  the  action  of  mercury  upon  the  liver,  see  PURGATIVES. 

The  experiments  of  I.  Brauer12  and  of  V.  Tirelli13  show  that  in  the  lower  ani- 
mals very  large  doses  of  mercurials  have  a  powerful  depressing  influence  upon  the 
central  nervous  system,  and  may  produce  death  by  respiratory  paralysis  ;  that  when 
smaller  doses  are  given  a  condition  of  nervous  ex'citement  is  produced,  with  in- 
crease of  the  tendon-reflexes,  followed  by  partial  paralysis  and  ataxia  ;  and  that  in 
chronic  poisoning  by  very  small  doses  continuously  administered  a  degeneration  of 
the  nervous  system  takes  place,  probably  beginning  in  the  anterior  motor  cells  of 
the  spinal  cord.  This  degeneration  appears,  however,  not  to  be  characteristic  of  the 
mercurial  poisoning,  but  to  be  similar  to  that  produced  by  phosphorus,  arsenic,  and 
various  other  poisons. 

Little  attention  has  been  paid  to  local  mercurial  poisoning,  but  A. 
W.  Foot M  has  reported  the  production  of  paralysis  of  the  muscles  of  the 
hand  and  forearm  by  contact  with  the  red  mercury  iodide  during  the 
rubbing  of  cattle  with  a  salve  containing  it.  It  is  asserted  that  in  some 
peculiar  persons  the  external,  and  even  the  internal,  use  of  small  amounts 
of  mercurials  will  produce  violent  eczema  or  other  skin-eruptions  (Alex- 
ander15). 

The  constitutional  action  of  mercury  shows  that  it  has  relations  to 
the  nutrition  of  the  whole  body.  The  alterations  in  the  blood,  the 
wasting,  the  perverted  functions  of  nerves  and  of  glandular  tissues,  the 
various  skin  eruptions,  all  point  to  a  profound  influence  upon  the  whole 
organism.  After  death  from  such  irritant  preparations  of  mercury  as 
corrosive  sublimate,  violent  diphtheritic  colitis  is  the  ordinary  lesion,  and, 
as  was  first  shown  by  Salkowsky,  structural  alterations  abound  in  the 
kidneys,  accompanied  by  a  peculiar  deposit  of  calcium  phosphate  :  that 
the  renal  lesions  may  be  produced  by  the  non-irritant  preparations 
of  mercury  has  been  shown  by  B.  Silva,16  who  has  found  true  desquama- 
tive  nephritis  in  dogs  to  which  calomel  had  been  given.  Felix  Klem- 
perer 1T  discusses  the  literature  of  the  subject  fully,  and  concludes  that  the 
successive  changes  in  the  kidneys  are  :  excessive  hyperaemia,  parenchy- 
matous  nephritis,  hemorrhagic  nephritis,  with  wide-spread  degeneration 


*  For  an  interesting  paper  in  regard  to  mercurialism   in  looking-glass  makers,  see 
article  by  Wollner  {Munch.  Med.  Wochen.,  July,  1892). 


488  GENERAL  REMEDIES. 

of  the  epithelium,  and  in  about  one-half  of  the  cases  deposits  of  chalky 
material.  Virchow 18  states  that  the  coexistence  of  distinct  renal  chalky 
deposits  with  diphtheritic  hemorrhagic  colitis  justifies  the  diagnosis  of 
corrosive  sublimate  poisoning,  but  Klemperer  affirms  that  this  condition 
can  be  produced  by  bismuth  and  some  other  poisons.  The  later  re- 
searches of  E.  Lentert'Med  to  a  similar  conclusion, — namely,  that  the 
calcification  of  the  kidneys  makes  the  diagnosis  of  corrosive  sublimate 
poisoning  very  probable  but  not  assured.  The  calcification  of  the  kid- 
neys, which  is  often  accompanied  by  true  calcareous  deposit  in  the  tubules, 
and  which  may  be  sufficient  to  cause  the  kidney  structure  to  cry  out 
under  the  scalpel,  was  attributed  by  Prevost 20  to  the  decalcification  of  the 
bones  ;  a  theory  which  seems  to  have  been  disproved  by  Klemperer 
(confirmed  by  Paul  Binet21). 

According  to  our  present  evidence,  it  does  not  seem  probable  that 
mercury  increases  the  nitrogenous  waste.  It  is  true  that  Hermann  von 
Boeck,22  in  a  case  of  mercurialization  in  a  man,  found  that  there  was  a  very 
slight  increase  in  the  elimination  of  nitrogen  during  the  mercurial  periods, 
but  H.  Schroder,23  and  Guttenberg  and  A.  Gurber,24  in  experiments 
made  upon  rabbits,  obtained  an  absolute  decrease  in  nitrogenous  elimina- 
tion during  mercurial  poisonings. 

THERAPEUTICS. — The  use  of  mercury  in  affections  of  the  liver  and  of 
the  alimentary  canal  is  fully  discussed  in  another  portion  of  this  treatise  ; 
and,  although  the  drug  has  been  used  for  almost  innumerable  purposes 
in  times  past,  it  seems  here  only  necessary  to  speak  of  its  action  as  an 
antiphlogistic  and  as  an  antisyphilitic. 

Antiphlogistic  Action. — The  use  of  mercury  in  inflammation  origi- 
nated towards  the  close  of  the  last  century  with  Robert  Hamilton,  and 
soon  became  universal  in  England  and  America.  It  is  a  matter  of  regret 
that  no  sufficient  analyses  of  the  blood  of  ptyalized  persons  have  been 
made  to  determine  exactly  what  are  the  changes  produced  in  the  vital 
fluid  by  mercury.  The  indications  are,  however,  very  strong  that  chief 
among  them  is  a  lessening  of  the  amount  of  fibrin.  As  is  well  known, 
increase  of  the  haemic  fibrin  is  one  of  the  most  characteristic  effects  of 
inflammation  :  consequently,  theory,  instead  of  being  opposed  to  the 
antiphlogistic  use  of  calomel,  affords  at  least  some  grounds  for  the  belief 
that  there  is  more  or  less  antagonism  between  the  processes  of  mercu- 
rialization and  of  inflammation. 

All  important  evidence  as  to  the  antiphlogistic  value  of  mercurials 
at  present  available  is  clinical,  and  even  of  this  it  seems  impossible  to 
find  much  that  is  very  exact  and  of  such  nature  as  to  exclude  possible 
fallacies.  It  is  the  enormous  mass  of  testimony  that  overrides  the  proba- 
bility of  fallacy.  It  is  the  general  judgment  of  the  profession,  founded 
upon  the  thousand  daily  observed  bedside  facts,  that  endorses  the  use  of 
mercury  as  an  antiphlogistic.  In  other  words,  our  knowledge  of  the  value 
of  mercurials  in  inflammation  at  present  is  clinical  rather  than  experi- 
mental, empirical  rather  than  scientific,  but  it  seems  scarcely  possible 


ALTERATIVES.  489 

that  it  is  not  correct.  There  is  one  inflammatory  affection — iritis — which, 
from  its  anatomical  relations,  is  completely  visible  at  all  stages  ;  and  the 
effects  of  the  drug  upon  its  processes  have  been  noted  from  day  to  day 
hundreds  of  times.  Oculists  are,  we  believe,  agreed  that  when  there  is 
a  marked  tendency  towards  the  exudation  of  lymph  in  this  disease,  mer- 
cury should  be  exhibited  until  ptyalism  is  induced. 

Of  all  inflammations,  those  of  the  serous  membranes  seem  to  be  most 
allied  to  iritis  ;  and  it  is  exactly  in  the  condition  above  spoken  of,  where 
there  is  a  tendency  to  fibrinous  exudations  in  pleuritis,  peritonitis,  and 
pericarditis,  that  mercury  is  so  constantly  employed  with  so  good  an 
effect.  In  parenchymatous  inflammations,  especially  \\\  pneumonia  and 
in  hepatitis,  mercury  has  been  used  with  asserted  advantage  by  many 
practitioners,  but  its  value  is  certainly  more  questionable  than  in  serous 
inflammations.  In  pseudo-membranous  angina  or  laryngitis,  and  in  true 
diphtheria,  the  mercurials  are  very  useful  remedies  ;  they  should  be 
given  in  small  repeated  doses,  preferably  in  the  form  of  dry  calomel  pow- 
ders, it  being  probable  that  the  good  effect  is  at  least  in  part  due  to  the 
diffusion  of  the  mercurial  over  the  diseased  surface  and  the  consequent 
antiseptic  influence.  There  is  much  doubt  as  to  the  exact  advantageous- 
ness  of  mercurials  in  endocarditis ;  but,  as  it  is  extremely  important,  if 
possible,  in  that  disease,  to  prevent  exudation,  and  as  mercury  is  the 
most  efficient  known  agent  for  effecting  this,  it  should  be  administered 
freely  and  at  once. 

In  whatever  disease  a  mercurial  is  administered  as  an  antiphlogis- 
tic, it  should  be  given  during  the  stage  of  exudation,  and  to  facilitate 
the  absorption  of  the  newly  organized  lymph  after  it  has  ceased  to  be 
thrown  out.  In  the  majority  of  cases  mercury  given  for  its  constitu- 
tional effects  should  be  combined  with  opium,  to  prevent  its  acting  on  the 
bowels. 

Calomel  should  not  be  used  in  adynamic  inflammations,  or  where  the 
exudation  is  serous  rather  than  fibrinous.  In  puerperal  peritonitis  it  has 
been  strongly  advocated  by  some  and  as  strongly  condemned  by  others, 
simply  because  there  are  two  varieties  of  the  disease,  the  sporadic  or 
tfhenic,  and  the  epidemic  or  asthenic ;  and  in  the  one  both  bleeding  and 
calomel  are  strongly  indicated,  while  in  the  other  they  are  effective  only 
for  evil. 

Mercury  as  an  Anti syphilitic. — The  literature  concerning  the  use  of 
mercury  in  the  treatment  of  syphilis  is  so  enormous  as  almost  to  defy 
analysis  ;  through  the  discussion,  however,  has  finally  been  reached  practi- 
cal unanimity  of  professional  opinion,  the  only  points  of  difference  being 
as  to  details  of  ' '  how' '  and  ' '  when' '  the  mercury  should  be  employed. 

Whenever  a  venereal  ulcer  offers  the  characteristics  of  a  true  chancre, 
mercury  should  be  exhibited.  Many  practitioners  believe  that  it  is  wiser 
for  diagnostic  purposes,  in  all  cases  of  doubt  as  to  the  character  of  the 
primary  sore,  to  withhold  the  mercury  until  secondary  manifestations 
appear.  Under  any  circumstances,  so  soon  as  the  diagnosis  of  syphilis 


490  GENERAL  REMEDIES. 

is  clearly  established,  mercury  should  be  employed  in  some  form  or 
other.  Our  own  practice  is  in  the  beginning  of  the  treatment  to  push 
the  mercury  to  the  point  of  mild  ptyalism, — i.e.,  to  the  production  of 
slight  evidences  of  constitutional  drug  action, — and  then  to  continue 
the  medicine  persistently  in  small  doses  for  at  least  eighteen  months,  in- 
creasing the  dose  up  to  mild  ptyalism  if  at  any  time  there  should  be  a 
recrudescence  of  the  symptoms. 

In  tertiary  syphilis  mercury  is  to  be  used  cautiously.  It  is  not,  how- 
ever, the  mere  length  of  time  that  has  elapsed  since  the  infection,  but  the 
condition  of  the  patient,  that  guides  the  judicious  practitioner.  So  long 
as  there  is  no  decided  cachexia,  if  the  patient  has  not  recently  been 
through  a  mercurial  course,  mercury  should  be  freely  used  when  the  local 
lesion  threatens  to  kill  directly  or  to  produce  organic  changes  in  a  vital 
organ.  Thus,  a  gumma  in  the  heart-wall,  in  the  upper  spinal  cord,  or  in 
some  vital  brain-region  may  imperatively  demand  active  mercurialization. 
We  have  twice  seen  a  patient  slowly  recovering  from  brain-syphilis  under 
the  influence  of  the  iodides  die  by  the  accident  of  an  epileptic  arrest  of 
respiration.  In  these  cases  the  more  rapid  resolution  of  the  gummatous 
masses  by  mercury,  had  that  drug  been  exhibited,  would  in  all  proba- 
bility have  prevented  the  fatal  fit.  In  hereditary  syphilis  a  prompt  mer- 
curial impression  offers  the  best  chance  of  relief.  At  any  stage  of  syph- 
ilis some  caution  and  judgment  should  be  used  in  the  administration 
of  mercury.  As  was  shown  by  Keyes,  the  small  dose  of  mercury  in 
infected  patients  frequently  acts  distinctly  in  increasing  the  number  of 
red  blood-disks.  Wilbouchewitch  found  that  the  mercurial  when  first 
exhibited  increased  the  number  of  red  blood-corpuscles  in  syphilitic 
patients,  but  after  a  time  appeared  to  produce  anaemia.  Whatever 
preparation  be  employed,  it  should  be  so  administered  as  to  cause  only 
signs  of  the  constitutional  action  in  the  mouth.  It  is  never  necessary 
to  ptyalize  the  patient  severely.  There  are  various  methods  by  which 
this  may  be  done.  That  most  frequently  employed,  because  most  con- 
venient, is  the  administration  of  small  doses  of  calomel  or  blue  pill  by  the 
mouth  :  from  one-fourth  to  one- half  grain  of  calomel,  or  twice  as  much 
of  the  blue  mass,  combined,  if  necessary,  with  opium,  to  prevent  its 
action  upon  the  bowels,  may  be  given  three  times  a  day,  and  increased  if 
required.  Instead  of  the  internal  use  of  the  mercurial,  the  system  may  be 
brought  under  its  influence  by  inunctions. 

In  practising  inunctions  it  is  essential  to  remember  that  when  mercury 
is  applied  to  a  hairy  surface  it  is  very  prone  to  cause  a  troublesome  irri- 
tation, due  to  inflammation  about  the  hair-follicles.  Indeed,  the  contin- 
uous application  of  the  mercurial  to  almost  any  surface  of  the  body  will 
cause  finally  an  eczematous  eruption.  Further,  when  the  skin  is  in  thor- 
oughly good  condition  it  absorbs  much  better  than  when  it  is  irritated. 
The  frequent  use  of  the  hot  baths  seems  also  to  aid  in  the  absorption,  and 
possibly  also  in  the  elimination  of  the  mercury  ;  and  the  good  effects  ob- 
tained at  the  Arkansas  and  other  thermal  springs  largely  depend  upon 


ALTERATIVES.  491 

the  frequent  employment  of  the  hot  bath  with  the  free  use  of  the  mer- 
curial. It  is  therefore  usually  better  to  have  the  inunction  practised  in 
the  evening,  after  the  patient  has  had  a  prolonged  bath  ;  and  in  cases  of 
great  urgency  the  baths  may  be  repeated  two  or  three  times  a  day,  so  as 
to  produce  free  sweating,  and  the  inunction  practised,  it  may  be,  twice 
a  day.  In  order  to  avoid  irritation  of  the  skin,  a  regular  order  should 
be  maintained  in  the  application,  as  follows  :  first  day,  inner  side  of  both 
upper  arms  ;  second  day,  inner  side  of  both  thighs  ;  third  day,  inner  side 
of  both  forearms  ;  fourth  day,  inner  side  of  both  legs  ;  fifth  day,  upon 
both  groins  ;  sixth  day,  upon  the  back  ;  seventh  day,  recommence  the 
series. 

The  advantage  of  inunction  is  that  the  digestion  is  less  apt  to  be  dis- 
turbed than  when  the  drug  is  exhibited  by  the  mouth  ;  *  the  disadvantages 
are  the  greater  or  less  publicity  which  it  entails,  the  trouble  which  it  in- 
volves, and  its  apparent  dirtiness.  In  private  practice  it  is  rarely  prac- 
tised except  in  the  case  of  infants,  when  the  mercurial  ointment  is  rubbed 
into  the  abdomen  and  armpits,  or  often  simply  smeared  upon  the  flannel 
roller  or  binder  which  usually  envelops  the  body.  The  mercurialization 
of  the  nurse,  with  the  object  of  affecting  the  child,  is  unjustifiable,  unless 
the  nurse  and  the  nursling  are  alike  diseased  :  indeed,  to  allow  a  syphilitic 
child  to  feed  at  the  breast  of  a  healthy  woman  is  a  crime. 

Mercury  may  be  used  hypodermically,  often  with  great  advantage,  in 
the  treatment  of  syphilis.  The  search  after  novelties  by  clinicians  and 
chemists  has  led  to  the  invention  of  very  many  new  preparations  and  the 
production  of  a  very  large  literature,  which  was  summarized  in  previous 
editions  of  this  work,  and  is  discussed  in  great  detail  in  current  mono- 
graphs on  syphilis.  As  the  result  of  much  experience,  however,  we  are 
confident  that  the  whole  matter  can  be  summed  up  in  a  single  sentence, 
— namely,  that  no  mercurial  preparation  has  any  distinct  advantage  over 
corrosive  sublimate  for  hypodermic  administration  ;  and  that  the  great 
mass  of  the  proposed  preparations,  including  all  those  which  contain  cal- 
omel, are  much  more  dangerous  than  is  the  corrosive  chloride.  From 
one-sixteenth  to  one-eighth  of  a  grain  of  the  bichloride  should  be  injected 
deeply  into  the  muscles  of  the  back  or  of  the  thigh  daily  or  every  other 
day,  according  to  the  needs  of  the  case  ;  care  being  exercised  to  see  that 
the  part  is  well  rubbed  immediately  after  the  injection,  so  as  to  dispel  the 
local  accumulation  of  fluid,  and  that  injections  are  not  given  on  successive 
days  in  places  near  to  one  another.  In  some  cases  very  pronounced  pain 

*  The  action  of  inunctions  is  usually  very  mild  and  tractable,  but  Von  Sackur  (Berl. 
Klin.  Wochensch.,  1892,  xxix.)  has  reported  a  case  of  death  in  six  days,  preceded  by 
symptoms  of  violent  irritation  of  the  stomach,  the  intestines,  and  the  kidneys,  with  furious 
gangrenous  ptyalism,  apparently  produced  by  a  single  inunction  with  mercurial  ointment. 
Ludwig,  of  Vienna,  in  an  examination  to  determine  the  distribution  of  mercury  given  by 
inunction,  found  that  it  was  most  abundant  in  the  kidneys,  liver,  and  spleen  ;  then  in  the 
alimentary  canal  (least  in  the  stomach  and  most  in  the  large  intestine).  In  the  muscles 
the  amounts  were  variable,  in  the  cerebrum  never  sufficient  to  be  weighed  (Internal. 
Klinisch.  Rundschau,  1892,  vi.). 


492  GENERAL   REMEDIES. 

is  produced  ;  this  can  be  overcome,  however,  by  injecting  one-quarter  of 
a  grain  of  cocaine  immediately  before  the  injection  of  the  mercurial  into 
the  same  spot.  The  advantages  of  hypodermic  medication  are  the 
rapidity  and  power  of  influence,  the  cleanliness,  and  the  avoidance  of 
gastro-intestinal  irritation. 

Mercury  is  sometimes  administered  in  secondary  syphilis  in  the  form 
of  fumigations.  The  patient  is  placed  upon  a  chair,  and  surrounded  by 
a  large  blanket  or,  better,  india-rubber  cloth,  so  arranged  as  to  fit  tightly 
around  his  neck  above,  and  below  to  encompass  the  chair.  The  mer- 
curial preparation  is  placed  upon  a  metal  plate,  heated  by  a  spirit-lamp, 
beneath  the  chair,  and  the  fumes  are  allowed  to  fill  the  space  around  the 
patient  inside  of  the  blanket.  The  heat  produced  generally  causes  the 
patient  to  sweat  profusely,  and  in  from  fifteen  minutes  to  half  an  hour  the 
lamp  should  be  withdrawn  and  the  patient  allowed  to  cool  off,  and  after 
a  time  be  put  to  bed  and  wrapped  up  in  blankets,  with  the  deposit  of 
mercury  still  adhering  to  the  skin.  The  fumigation  may  be  practised 
every  other  night,  or  at  longer  intervals,  and  is  believed  by  some  to  be 
especially  useful  in  cases  of  secondary  skin  eruptions.  Calomel,  black 
oxide,  and  cinnabar  are  the  preparations  generally  used  ;  care  must  be 
exercised  that  the  patient  do  not  breathe  the  fumes. 

In  advanced  secondary  and  tertiary  syphilis  the  mercurial  iodides, 
given  by  the  mouth,  are  often  very  useful,  but  the  combination  of  the 
corrosive  sublimate  and  the  potassium  iodide  is  in  many  cases  still  more 
efficient.  Usually  not  more  than  one-twelfth  of  a  grain  of  the  bichloride 
should  be  exhibited,  three  times  a  day. 

It  appears  to  be  established  that  certain  disagreeable  and,  perchance, 
serious  effects  may  be  produced  by  mercurials  when  freely  and  continu- 
ously used  in  the  treatment  of  syphilis,  against  which  the  practitioner 
must  be  on  his  guard.  The  most  important  of  these  is  nephritis,  with 
its  consequent  albuminuria.  According  to  Heller,25  the  safest  method  of 
mercurialization,  so  far  as  the  kidneys  are  concerned,  is  by  the  hypoder- 
mic employment  of  corrosive  sublimate  ;  the  most  dangerous,  probably, 
being  the  use  of  inunctions.  A  very  rare  complication  which  has  been 
attributed  to  the  mercury  is  polyneuritis,  which  has  especially  been  noted 
after  the  very  free  use  of  mercurial  inunctions.* 

ADMINISTRATION. — The  following  preparations  contain  metallic  mer- 
cury : 

UNGUENTUM  HYDRARGYRI.  U.  S. — Blue,  or  Mercurial,  Ointment  is 
made  by  triturating  mercury  with  suet  and  lard  until  the  metal  is  extin- 
guished,— /.<?.,  until  a  portion  of  the  mass  rubbed  upon  a  piece  of  paper 
exhibits  no  globules  under  a  magnifying  power  of  ten  diameters.  Mer- 
curial ointment  is  soft,  of  a  bluish  color,  becoming  darker  by  age  ;  it 
contains  half  its  weight  of  mercury.  It  is  used  to  make  a  constitutional 

»  See  Leyden  (Deutsch.  Med.  Wochen.,  1893,  xix.)  and  R.  von  Engel  (Prager  Med. 
Wochen.,  1894,  xix.). 


ALTERATIVES.  493 

impression,  and  also  locally  as  a  resolvent,  in  cases  of  en.arged  indurated 
glands.  The  oleate  of  mercury  (OLEATUM  HYDRARGYRI — twenty  per 
cent. ,  U.  S. )  is  preferred  by  some  practitioners. 

EMPLASTRUM  HYDRARGYRI.  U.  S. — Mercurial  Plaster  contains  mer- 
cury, oleate  of  mercury,  hydrous  wool-fat,  and  lead  plaster,  and  is  used  as 
a  resolvent  in  indurated  glands,  enlarged  chronically  inflamed  joints,  etc. 

MASS  A  HYDRARGYRI.  U.  S. — Mass  of  Mercury — Blue  Mass  is  made 
by  extinguishing  mercury  with  honey  and  other  inert  substances.  It 
contains  one-third  its  weight  of  the  metal,  and  is  used  for  the  same  pur- 
pose as  calomel,  but  is  milder.  Dose  :  purgative,  five  to  ten  grains 
(0.3-0.6  Gm. );  alterative,  one  to  three  grains  (0.06-0.18  Gm. ).  Blue 
Pills  usually  contain  each  three  or  five  grains  of  the  mass. 

HYDRARGYRUM  CUM  CRETA.  U.  S. — Mercury  with  Chalk. — Gray 
Powder  is  made  with  chalk.  It  is  a  smooth,  grayish  powder,  and  is 
similar  to  blue  mass  in  its  medical  properties,  strength,  and  dose. 

HYDRARGYRI  CHLORIDUM    MITE— MILD    MERCUROUS   CHLORIDE. 

U.S. 

Calomel  is  a  white,  insoluble,  tasteless  and  odorless,  heavy  powder. 

PHYSIOLOGICAL  ACTION. — Owing  to  the  great  insolubility  of  calomel, 
a  good  deal  of  discussion  has  occurred  as  to  the  way  by  which  it  finds 
entrance  into  the  system. 

According  to  the  theory  of  Mialhe,*6  calomel  is  converted  by  the  chlorides  of 
the  stomach  into  corrosive  sublimate,  and  as  such  is  absorbed.  The  action  of  calo- 
mel upon  man  is  so  different  from  that  of  corrosive  sublimate  as  to  render  this  theory 
exceedingly  improbable,  and,  at  temperatures  even  higher  than  that  of  the  stomach, 
Mialhe  was  never  able  to  obtain  the  formation  of  more  than  a  sixteenth  of  a  grain 
of  the  sublimate  by  the  gastric  juices.  Further,  Bucheim,  Oettingen,  and  Winkler* 
affirm  that  this  conversion  does  not  occur  at  all  at  the  temperature  of  the  body. 
Jeannel "  has  confirmed  this,  and  has  suggested  what  seems  to  be  the  way  in  which 
calomel  is  absorbed.  He  finds  that  when  the  mercurous  chloride  is  placed  in  a  solu- 
tion of  an  alkaline  carbonate  it  is  decomposed  and  the  gray  oxide  precipitated.  A 
small  portion,  however,  of  the  latter  is  held  in  solution,  as  much  as  0.02  part  in  fifty 
parts  of  water  (by  weight)  ;  and  if  a  fatty  oil  be  mixed  with  the  alkaline  solution  a 
very  large  part  of  the  mercury  is  dissolved. 

It  would  appear  certain  that  calomel  entering  the  stomach  and  escaping 
unchanged  into  the  duodenum  is  decomposed  by  the  alkaline  contents 
of  the  intestines  and  dissolved  by  the  fatty  matters  usually  present.  It  is 
possible  that  at  times,  when  the  stomach  contains  more  than  usual  of 
chlorides  and  of  hydrochloric  acid,  a  very  small  portion  of  the  calomel 
may  be  converted  into  corrosive  sublimate,  and  also  that  when  there  is 
an  excess  of  sulphuretted  hydrogen  in  the  alimentary  canal  a  soluble 
sulphide  may  be  formed. 

The  influence  of  calomel  upon  the  system  has  been  sufficiently  dis- 
cussed. It  remains  only  to  state  that  its  freedom  from  all  irritant  prop- 
erties is  shown  when  taken  internally  or  when  used  externally.  Prob- 

*  Quoted  by  StillS  (  Therapeutics,  ad  ed.,  655). 


494  GENERAL  REMEDIES. 

ably  no  single  dose  of  it  is  capable,  in  the  average  man,  of  acting  as 
a  violent  poison,  since  it  is  stated  that  in  the  Western  United  States 
it  is  very  frequently  taken  in  teaspoonful  doses,  that  sixteen  grains  of 
it  will  act  as  vigorously  as  an  ounce,  and  that  a  pound  of  it  has  been 
given  in  a  case  of  cholera  without  visible  effect.  *  It  seems  to  us  most 
probable  that  the  absence  of  serious  results  from  these  heroic  amounts 
is  due  to  the  alimentary  canal  being  unable  to  dissolve — i.e. ,  to  absorb 
— the  calomel.  F.  D.  Lente  has  affirmed  that  given  in  enormous  dose 
the  drug  acts  as  a  sedative  and  does  not  produce  mercurialization.  For 
use  of  calomel  as  a  diuretic  and  in  dropsy,  see  DIURETICS. 

ADMINISTRATION. — When  it  is  desired  to  produce  constitutional  mer- 
curialization, the  dose  of  calomel  is  a  half  to  one  grain  ;  as  a  purga- 
tive, from  six  to  ten  grains  are  administered,  followed  in  six  hours  by 
Seidlitz  powder,  or  other  saline,  if  required  ;  or,  as  is  preferred  by  some 
practitioners,  a  quarter  of  a  grain  is  given  every  hour  until  three  grains 
are  taken  or  purgation  is  induced.  Minute  doses  (one-sixth  of  a  grain) 
of  calomel  given  every  hour  afford  a  very  good  method  of  impressing 
the  system  rapidly.  When  it  is  desired  to  get  its  constitutional  influence, 
it  is  generally  necessary  to  conjoin  opium  with  it,  to  prevent  purging. 

HYDRARGYRI  CHLORIDUM  CORROSIVUM— CORROSIVE  MERCURIC 

CHLORIDE.     U.  S. 

Mercury  Bichloride,  or  Corrosive  Sublimate,  occurs  in  the  form  of 
colorless  crystals,  or  of  white,  semi-transparent,  crystalline  masses,  of  an 
acrid,  metallic,  styptic,  and  very  persistent  taste,  soluble  in  sixteen  parts 
of  cold  and  in  two  of  boiling  water.  It  is  at  once  distinguished  from  the 
other  mercurial  preparations  by  its  color,  taste,  and  solubility,  and  by 
its  forming  a  yellow  precipitate  with  lime-water. 

PHYSIOLOGICAL  ACTION. — Corrosive  sublimate  is  a  violent  irritant, 
and  in  concentrated  form  caustic.  When  given  in  small  repeated  doses, 
although  capable  of  inducing  salivation,  it  is  less  apt  to  do  so  than  is 
calomel  or  blue  pill.  In  overdoses  it  produces  symptoms  of  irritant 
poisoning  of  a  severity  proportionate  to  the  dose.  If  the  latter  be  small, 
the  manifestations  may  be  only  some  nausea,  slight  burning  in  the  stom- 
ach, colicky  pains  in  the  abdomen,  and  diarrhoea.  After  large  doses  these 
symptoms  are  intensified.  The  subject  first  experiences  a  peculiar  metal- 
lic, coppery  taste  at  or  shortly  after  swallowing  the  poison.  If  the  solu- 
tion be  concentrated,  deglutition  is  interfered  with  by  a  spasm  of  the 
muscles  of  the  throat  and  larynx,  causing  a  feeling  of  suffocation,  and 
sometimes  even  the  rejection  of  the  draught.  Then  burning  pains  are 
experienced  in  the  oesophagus  and  stomach,  followed  by  violent  vomiting, 
at  first  mucous,  then  bilious,  and  finally  bloody,  and  by  severe  abdominal 
pain  and  tenderness,  with  profuse  purging,  at  first  serous  in  character,  but 
afterwards  affording  only  small,  mucous,  bloody  stools,  which  are  often 

*  George  B.  Wood's  Therapeutics,  ii.  565 


ALTERATIVES.  495 

voided  with  much  straining.  The  breath  generally  becomes  fetid  and 
offensive  in  a  very  short  time.  In  the  course  of  two  or  three  hours,  very 
rarely  in  less  than  an  hour,  collapse  occurs,  with  small,  frequent,  irregu- 
lar pulse,  pinched,  anxious  face,  cold  extremities,  and  finally  death,  pre- 
ceded, it  may  be,  by  fainting,  convulsions,  and  coma.  The  urine  is  very 
much  lessened  in  quantity,  is  sometimes  albuminous,  or  even  bloody, 
and  not  rarely  is  suppressed.  If  the  patient  survive  several  days,  a 
petechial  eruption  may  appear,  and  salivation  sometimes,  but  not  always, 
occurs.  In  some  cases,  after  the  collapse  there  is  an  attempt  at  a  febrile 
reaction,  which  soon,  however,  gives  place  to  a  second  and  fatal  prostra- 
tion. When  recovery  occurs  after  severe  poisoning,  the  convalescence  is 
slow  and  protracted. 

In  regard  to  chronic  poisoning  with  corrosive  sublimate,  sufficient  has 
been  said  under  the  general  heading,  except  that  colicky  pains  and  ab- 
dominal disturbance  are  more  apt  to  occur  with  it  than  with  the  less  irri- 
tating preparations.  Hemorrhagic  nephritis  has  been  noted  in  a  number 
of  cases  (H.  C.  Wood,  Jr.32).  Arnozan28  asserts  that  chronic  catarrh  of 
the  excretory  ducts  of  the  pancreas  is  a  pronounced  lesion  in  chronic 
poisoning  of  animals.  It  should  be  looked  for  in  man,  and  its  presence 
might  be  of  medico-legal  value. 

Severe  purging,  and  even  fatal  poisoning,  may  result  from  a  single 
external  application  of  this  preparation  of  mercury,*  and  in  animals 
killed  by  hypodermic  injections  of  it  (see  experiments  of  J.  Rosenbach29), 
diarrhoea  and  other  indications  of  gastro- intestinal  irritation  are  prominent 
symptoms, — facts  which  indicate  that  the  bichloride  is  eliminated  un- 
changed from  the  alimentary  canal.  Dose,  one-hundredth  to  one-eighth 
of  a  grain  (0.0006—0.008  Gm. ). 

HYDRARGYRI  IODIDUM  FLAVUM. —  Yellow  Mercurous  Iodide,  U.S., 
is  a  greenish-yellow,  odorless,  and  tasteless  powder,  insoluble  in  water, 
ether,  and  alcohol.  Compared  with  the  biniodide  or  the  bichloride,  it  is 
a  mild  preparation,  and  has  been  used  to  produce  constitutional  impression 
in  syphilis,  especially  when  of  long  standing.  The  potassium  iodide  con- 
verts it  into  the  biniodide  and  metallic  mercury,  and  should,  therefore, 
never  be  given  in  combination  with  it.  Alterative  dose  one-fourth  of  a 
grain  (0.016  Gm. )  three  times  a  day,  increased  to  a  grain  if  necessary 
(0.06  Gm.). 

HYDRARGYRI  IODIDUM  RUBRUM  U.  S. — Red  Mercuric  Iodide  is  a 
scarlet  red  powder,  almost  insoluble  in  water,  sparingly  soluble  in  alcohol. 
It  is  a  powerful  local  irritant,  producing,  when  taken  in  overdoses,  symp- 

*  See  case  reported  by  Meeres  {Lancet,  Sept.  16,  1871),  in  which  a  solution  (two 
grains  to  one  fluidrachm)  was  applied  with  a  camel's-hair  brush  to  the  head  of  a  child 
nine  years  old,  for  the  cure  of  tinea  tonsurans.  The  symptoms  were  diarrhoea,  profuse 
salivation,  and  great  prostration,  ending  in  death.  Washing  out  the  vagina  with  a  solu- 
tion of  corrosive  sublimate,  has  caused  severe  and  even  fatal  poisoning.  (See  H.  C. 
Wood,  Jr. 32.)  Marx  and  Sorge  33  found  that  in  pregnant  animals  acute  corrosive  subli- 
mate poisoning  causes  injury  not  only  to  the  placenta  but  also  to  the  fcetal  kidney. 


496  GENERAL  REMEDIES. 

toms  and  results  very  similar  to  those  caused  by  corrosive  sublimate.  It 
is  much  used  in  tertiary  syphilis  and  in  syphilitic  rheumatism  ;  also  to 
some  extent  as  a  local  application  in  lupus.  It  is  much  more  active  than 
is  the  protiodide,  and  should  be  administered  as  cautiously  and  in  the 
same  doses  as  is  corrosive  sublimate. 

The  U.  S.  Pharmacopoeia  also  recognizes  the  following  preparations 
of  mercury  : 

The  mercuric  oxide  occurs  in  two  forms,   the  Yellow  and  the  Red 

Oxide     (HYDRARGYRI    OXIDUM     FLAVUM,    HYDRARGYRI     OXIDUM    Ru- 

BRUM):  both  are  used  upon  ulcers,  chancres,  etc.,  for  their  local  effects, 
and  are  stimulant  and  alterative  when  diluted,  mildly  escharotic  when 
in  powder.*  From  Hydrargyri  Oxidum  Flavum  is  made  the  oleate 
(OLEATUM  HYDRARGYRI — twenty-five  per  cent.,  U.  S. ).  The  Red  Pre- 
cipitate Ointment  (UNGUENTUM  HYDRARGYRI  OXIDI  RUBRI — ten  per 
cent,  U.  S. ),  the  Ointment  of  the  Yellow  Oxide  (UNGUENTUM  HY- 
DRARGYRI OXIDI  FLAVI — ten  per  cent.,  U.  S. ),  and  the  Citrine  Oint- 
ment (UNGUENTUM  HYDRARGYRI  NITRATIS — seven  per  cent,  U.  S. ) 
very  generally  require  dilution  with  lard,  and  are  much  used  in  chronic 
skin  affections,  in  obstinate  conjunctivitis,  in  psorophthalmia,  etc.,  the 
plaster  (EMPLASTRUM  HYDRARGYRI,  U.  S.,  thirty  per  cent). 

Turpeth  Mineral,  or  Yellow  Mercuric  Subsulphate,  which  was  for- 
merly official — a  lemon-yellow  powder,  sparingly  soluble  in  water — is 
a  compound  of  uncertain  composition,  which  was  at  one  time  used  as 
an  emetic  in  croup.  It  is,  however,  a  very  dangerous  remedy,  since, 
if  it  fail  to  vomit,  it  may  cause  a  fatal  gastro-enteritis,  especially  in  the 
young  child.  Two  cases  of  such  character  are  recorded  by  A.  Mc- 
Phedran.30  Forty  grains81  have  caused  death  in  the  adult ;  profuse  sali- 
vation came  on  in  six  hours.  Dose  as  an  alterative,  a  quarter  to  half  a 
grain  (0.016-0.032  Gm. );  as  an  emetic,  for  a  child  two  years  old,  two 
grains  (0.13  Gm. ),  repeated  in  fifteen  minutes,  if  necessary. 

White  Precipitate,  or  Ammoniated  Mercury  (HYDRARGYRUM  AMMO- 
NI ATUM,  U.  S. ) ,  is  a  white  complex  powder,  made  by  precipitating  the 
bichloride  with  water  of  ammonia.  It  is  used  in  the  form  of  ointment 
(UNGUENTUM  HYDRARGYRI  AMMONIATI — ten  per  cent.,  U.S.)  as  a 
local  application  in  various  skin  affections. 

Black  Wash  and  Yellow  Wash,  two  non-official  but  favorite  prepara- 
tions, are  respectively  made  by  the  addition  of  a  drachm  of  calomel  to  a 
pint  of  lime-water,  and  of  half  a  drachm  of  corrosive  sublimate  to  a  pint 
of  lime-water.  They  depend  for  their  virtues  upon  the  black  and  yellow 
oxides  of  mercury,  and  are  used  exclusively  as  local  applications  to 
chancres  and  other  syphilitic  rtlcers.  The  yellow  wash  is  much  the  more 
stimulating  of  the  two. 

*  For  severe  poisoning  by  yellow  oxide,  see  Brit.  Med.  Journ.,  Sept.  1889. 


ALTERATIVES.  497 

AURI    ET    SODII    CHLORIDUM.     U.  S.— GOLD    AND    SODIUM 

CHLORIDE. 

This  salt  of  gold,  which  may  be  obtained  in  large,  golden-yellow, 
prismatic  crystals,  is,  according  to  the  requirements  of  the  U.  S.  Phar- 
macopoeia, a  slightly  deliquescent  powder,  having  an  odorless  but  a 
saline  and  metallic  taste.  It  is  freely  soluble  in  water. 

PHYSIOLOGICAL  ACTION. — The  precise  action  of  the  preparations  of 
gold  upon  the  animal  organism  is  not  understood,  but  it  is  probable  that 
the  soluble  preparations  are  mostly  irritant  poisons,  whilst  the  insoluble 
preparations  are  either  not  poisonous  or  else  act  slowly  upon  the  general 
system.  It  is  stated  that  gold  and  sodium  chloride,  in  overdose,  pro- 
duces pain,  inflammation,  and  even  ulceration  of  the  stomach  and  bowels, 
and  otherwise  acts  as  a  corrosive  poison.  It  is  affirmed  that  the  gold 
preparations,  in  moderate  doses,  cause  increased  fulness  and  frequency 
of  the  pulse,  and  augment  the  urine  and  insensible  perspiration,  with- 
out interfering  with  the  appetite  or  the  regular  action  of  the  bowels  ;  but 
that,  if  the  dose  be  pushed  too  far,  general  irritation  is  apt  to  be  pro- 
duced, and  inflammation  to  seize  upon  some  organ,  according  to  the 
predisposition  of  the  individual,  and  fever  is  developed. 

THERAPEUTICS. — Although  gold  and  sodium  chloride  has  been  largely 
used  by  clinicians,  its  exact  action,  and  indeed  its  real  value,  are  still 
matters  of  doubt.  It  is  believed,  however,  by  many  to  have  a  distinct 
influence  upon  the  general  nutrition,  and  especially  upon  the  nutrition 
of  the  nervous  system.  The  various  uses  of  it  may  be  discussed  under 
distinct  headings. 

First,  as  a  Nerve  Tonic. — It  has  been  used  quite  largely,  especially 
by  gynaecologists,  many  of  whom  think  that  it  has  a  specific  direction 
to  the  genital  organs,  in  neurasthenia,  in  hysteria,  in  neuralgia, — espe- 
cially in  ovarian  neuralgia  and  in  ovarian  irritation, — and  in  other  con- 
ditions of  depressed  nerve-power.  It  has  also  been  much  used  as  an  alter- 
ative tonic  in  the  treatment  of  the  alcohol  habit.  It  is  true  *  that  analysis 
has  shown  that  most,  if  not  all,  of  the  advertised  gold  nostrums  for  the 
cure  of  alcoholism  contain  no  gold  in  any  form  ;  but  the  most  reliable 
obtainable  information  indicates  that  in  the  Keeley  Institutes,  so  called, 
the  treatment  consists  chiefly  of  the  administration  of  varying  doses  of 
the  gold  and  sodium  chloride,  with  hypodermic  injections  in  the  in- 
terim (every  three  hours)  of  minute  doses  of  atropine  and  strychnine. 
It  is  incredible  that  any  medication  can  work  moral  reformation,  and 
the  extraordinary  results  which  have  been  sometimes  achieved  in  the 
Keeley  Institutes  are  balanced  by  numerous  failures,  and  have  probably 
been  only  in  small  part,  if  at  all,  directly  due  to  the  medical  treatment. 
Nevertheless,  in  some  trials  which  we  have  made  it  did  appear  that  the 
treatment  just  spoken  of,  by  strengthening  the  nervous  system  and  bring- 
ing about  a  general  increase  of  nutritive  tone,  aided  persons  who  were  de- 

*  See  Alcoholism  audits  Treatment,  J.  E.  Usher,  1892. 
32 


498  GENERAL  REMEDIES. 

termined  upon  reform.  It  has  seemed  to  us  that  the  gold  salt  has  some 
influence  in  overcoming  the  physical  conditions  of  chronic  alcoholism. 

Secondly,  as  an  Alterative. — The  gold  and  sodium  chloride  has  been 
commended  by  various  practitioners  in  scrofula,  advanced  syphilis, 
chronic  rheumatism,  and  chronic  diseases  of  the  joints.  Charles  G.  Stock- 
ton asserts  that  it  has  a  special  influence  upon  the  lithaemic  and  fatty 
degenerations  which  are  prone  to  occur  in  advanced  middle  life.  The 
salt  is  also  employed  with  alleged  excellent  results  in  the  various  spinal 
and  cerebral  scleroses. 

ADMINISTRATION. — The  gold  and  sodium  chloride  may  be  given  in 
solution  or  in  pill,  in  doses  of  one-twelfth  of  a  grain,  increased  to  one- 
sixth  or  even  one-fourth  (0.005-0.016  Gm. )  three  times  a  day.  It  may 
also  be  administered  hypodermically,  producing  some  pain,  but  usually 
no  serious  or  permanent  local  irritation.  In  many  cases  in  which  it  has 
been  used  the  moral  effect  of  the  hypodermic  injection  has  probably  been 
greater  than  the  direct  influence  of  the  remedy. 

INSOLUBLE  GOLD  PREPARATIONS. — The  oxide,  iodide,  and  other  insoluble 
preparations  of  gold  have  been  recommended  as  alteratives  in  scrofula,  skin 
diseases,  and  secondary  syphilis  of  various  forms,  in  doses  of  from  one-fifteenth  to 
one-tenth  of  a  grain,  three  times  a  day. 

IODUM— IODINE.     U.  S. 

Iodine  is  a  soft,  friable,  opaque  substance,  occurring  in  crystalline 
scales  with  a  semi-metallic  lustre  and  of  a  bluish-black  color.  Its  odor 
resembles  that  of  chlorine  ;  its  taste  is  hot  and  acrid.  It  is  somewhat 
volatile  at  ordinary  temperatures,  but  when  heated  to  237.2°  F.  melts 
and  emits  the  beautiful  purple  or  violet  vapor  to  which  it  owes  its 
name.  It  is  freely  soluble  in  glycerin,  alcohol,  and  ether,  but  requires 
five  thousand  times  its  weight  of  water  to  dissolve  it.  With  starch 
it  strikes  a  deep  blue  color,  and  this  test  is  so  delicate  that  it  will  indi- 
cate the  presence  of  iodine  in  four  hundred  and  fifty  thousand  times  its 
weight  of  water.  In  testing  animal  liquids,  such  as  urine,  for  iodine,  a 
small  quantity  of  nitric  acid  should  be  added  to  insure  its  being  free  in  the 
liquid. 

Local  Action. — Iodine,  when  applied  to  any  part  of  the  body,  acts  as 
a  very  powerful  irritant,  or,  if  in  highly  concentrated  form,  as  a  mild 
caustic.  The  tincture  stains  the  skin  yellow,  and  causes,  if  applied  with 
sufficient  freedom,  smarting,  some  erythematous  inflammation,  and  finally 
desquamation.  Its  repeated  application  blisters  and  destroys  the  cuticle. 
Upon  mucous  membranes  its  action  is  more  intense  than  upon  the  skin. 

Absorption  and  Elimination. — Iodine  and  its  salts  are  certainly  ab- 
sorbed, entering  into  all  the  tissues  and  fluids  of  the  body,  and,  contrary 
to  the  old  assertions,  even  into  serous  and  other  exudates  (G.  Leuch1). 
The  iodine  is  eliminated  partly  as  an  alkaline  iodide  and  partly  in  organic 
combination  (E.  Harnack2).  Organic  combinations  of  iodine  used  in 
medicine  are  probably  broken  up  in  the  system,  since  Oscar  Schulz ' 


ALTERATIVES.  499 

found  that  after  the  ingestion  of  the  gluten-peptone-iodine  preparation  of 
C.  Paal,  the  iodine  escaped  from  the  kidneys  without  the  peptone.  Iodine 
has  been  found  in  the  secretions  of  the  skin  ( R.  W.  Taylor 4) ,  and,  ac- 
cording to  See,5  may  exist  in  the  saliva  after  it  has  disappeared  from  the 
urine.  It  probably  escapes  also  to  some  extent  from  the  intestines,  but 
its  chief  channel  is  through  the  kidneys.  In  a  patient  under  our  care, 
taking  daily  three  hundred  and  sixty  grains  of  the  potassium  iodide, 
John  Marshall  recovered  daily  two  hundred  and  sixty-five  grains  from  the 
urine  (see  also  Ehlers6).  Se"e  states  that  the  elimination  is  apt  to  be 
irregular,  so  that  the  drug  may  accumulate  in  the  system. 

General  Action. — When  taken  internally,  a  single  moderate  dose  of 
iodine  causes  merely  some  gastric  uneasiness  and  a  disagreeable  metallic 
taste  in  the  mouth  ;  when  larger  amounts  are  ingested,  the  gastric  uneasi- 
ness may  be  intensified  into  violent  vomiting,  with  increased  salivary  flow, 
abdominal  pains,  and  even  purging.  In  sufficient  quantity  it  is  a  poison, 
although  very  few  deaths  have  been  recorded  as  caused  by  it.  The 
symptoms  produced  by  toxic  doses  taken  into  the  stomach  are  burning 
pain  in  the  oesophagus  and  stomach,  vomiting,  purging,  smallness  of  the 
pulse,  general  deadly  pallor,  lessening  or  arrest  of  the  urinary  secretion, 
sometimes  violent  excitement  with  convulsions,  and  collapse.  Twenty 
grains  of  iodine  are  said  to  have  caused  death,  and  two  drachms  and  a 
half  have  been  recovered  from.*  The  vomit  is  yellowish  brown  or,  if 
starchy  matters  have  beea  present  in  the  stomach,  bluish.  The  injection 
of  iodine  into  the  cavities  of  the  body  for  therapeutic  use  has  several 
times  been  followed  by  cyanosis,  thready  pulse,  repeated  vomiting  of 
matters  containing  iodine,  excessive  thirst,  salivation,  difficult  urination, 
swelling  of  the  eyelids,  laryngeal  pain,  various  eruptions  upon  the  skin, 
high  fever,  and  album inuria.  Sudden  death  may  take  place  after  some 
days  from  heart-failure. 

E.  Rose 7  records  a  death  following  injection  of  iodine  into  an  ovarian  cyst. 
Very  soon  after  it  was  given  there  ensued  severe  thirst,  with  great  dryness  of  the 
throat  and  mouth,  and  then  painless  vomiting  of  watery  matters  containing  iodine. 
The  whole  surface  became  very  pale,  the  extremities  cyanosed,  the  radial  pulse  very 
frequent,  but  so  small  that  it  could  not  be  counted,  the  urine  very  scanty,  dark 
brown,  and  rich  in  iodine.  After  a  time  reaction  occurred.  For  three  days  the 
vomiting  persisted,  the  pulse  was  very  frequent,  full  and  hard,  and  the  cheek  put 
on  the  glow  of  high  fever,  but  the  temperature  did  not  rise  above  37. 18°  C.  On 
the  fourth  day  exanthematous  blotches,  not  disappearing  on  pressure,  developed  on 
the  skin  and  in  the  mouth,  the  sputa  became  bloody,  and  menstruation  occurred 
two  and  half  weeks  too  soon.  The  urine  remained  scanty,  and  on  the  eighth  day, 
when  all  other  symptoms  save  swelling  of  the  parotids  had  disappeared,  still  con- 
tained iodine,  and  was  albuminous.  On  the  tenth  day,  in  the  midst  of  apparent 
convalescence,  the  patient  died  suddenly.  In  a  case  reported  by  W.  O.  Culpeper 8 
two  drachms  of  a  tincture  used  externally  on  a  child  of  eleven  years  destroyed  all 
the  skin  from  above  the  knees  to  below  the  ankles.  After  twenty-four  hours  there 
developed  headache,  backache,  some  diarrhoea,  vomiting,  great  thirst,  constant 

*  For  cases,  see  Woodman  and  Tidy,  also  Munchener  Med.  Wochenschr.,  Feb.  1887. 


5oo  GENERAL  REMEDIES. 

desire  to  urinate,  suppression  of  urine,  priapism,  and  giddiness  ;  finally  there  ensued 
dysentery  without  rise  of  temperature,  hiccough,  hemorrhage  from  the  bowels, 
and  great  giddiness  ending  in  death  on  the  sixth  day. 

In  the  experiments  of  Jorg  and  his  pupils,  doses  of  iodine  of  a  grain  to 
a  grain  and  a  half  gave  rise  to  colicky  pains,  increased  appetite,  watery 
stools,  an  increased  secretion  of  urine,  malaise,  and  some  headache. 
When  the  dose  was  augmented  to  two  grains,  a  diffused  sense  of  heat  and 
sexual  excitement  were  superadded.  Other  observers  have  noted  this 
abnormal  sexual  excitement,  and  some  have  stated  that  at  times  it  is  suc- 
ceeded by  atrophy  of  the  mammae  or  of  the  testicles.  Stille  affirms  that 
the  menstrual  flow  may  become  excessive,  or  that  during  pregnancy 
abortion  may  be  caused.  Very  large  quantities  of  iodine  are  asserted  to 
have  been  taken  \vithout  serious  results.  Julia  de  Fontenelle  *  tells  of  a 
man  who  took  two  and  a  half  drachms  of  iodine  without  experiencing  any 
remarkable  effects,  and  Magendie  relates  the  case  of  a  child  four  years 
old  who  swallowed  ten  grains  without  serious  consequences,  f 

In  the  experiments  of  A.  Hoyges  and  Binz,9  preparations  of  iodine, 
potassium  iodide,  and  iodoform  in  fatal  doses  produced  in  the  lower  ani- 
mals wide-spread  fatty  degenerations. 

If  full  doses  of  iodine  be  exhibited  continuously  for  a  length  of  time, 
a  train  of  phenomena  result,  known  as  lodism.  In  regard  to  these  there 
has  been  a  good  deal  of  difference  of  opinion  and  statement,  a  difference 
which  seems  explainable  only  upon  the  supposition  that  different  indi- 
viduals are  differently  affected  by  the  drug.  Rilliet  (Trousseau's10  re- 
port on  his  memoir),  who  has  had  wide  opportunities  and  has  apparently 
studied  the  subject  very  closely,  describes  three  forms  of  iodic  intoxica- 
tion :  first,  that  in  which  the  symptoms  are  those  of  gastric  irritation  ; 
second,  that  characterized  by  nervous  troubles,  neuralgia,  ringing  in  the 
ears,  convulsive  movements,  disturbed  intellection,  with  coryza,  ophthal- 
mia, salivation,  vomiting,  diarrhoea,  polyuria,  and  cutaneous  eruptions, 
and  in  some  cases  atrophy  of  the  mammae  in  the  female  and  of  the  testi- 
cles in  the  male  ;  J  third,  iodic  cachexia,  caused  either  by  iodine  or  potas- 
sium iodide  continuously  used  for  many  months.  It  is  said  to  be  most 
easily  induced  in  goitrous  persons,  and  is  characterized  by  rapid  emacia- 
tion, commencing  mostly  in  the  face,  and  severe  nervous  palpitations  of 
the  heart,  with  excessive  appetite,  which  sometimes  precedes  and  some- 
times follows  the  loss  of  flesh.  So  long  as  the  drug  continues  to  be 
taken,  these  symptoms  continue  to  progress,  and  after  a  time  hysteria  or 
hypochondriasis,  with  insomnia,  manifests  itself.  The  goitre,  the  mammae, 
and  the  testicles  waste  away  together  ;  but  if  the  medicine  be  suspended 
and  health  gradually  returns,  while  the  abnormal  growth  reappears  the 

*  Quoted  by  Stille  (  Therapeutics,  ii.  731). 

t  For  an  elaborate,  careful  study  of  the  action  of  large  toxic  doses  of  iodine  upon  the 
lower  animals,  see  Hoffmann  und  Schwalbe's  Jahresberichl,  1879,  199. 
J  For  a  case  of  wasting  of  the  testicles,  see  Phila.  Med.  Times,  iv.  661. 


ALTERATIVES.  501 

sexual  glands  remain  wasted.  It  is  probable  that  some  of  the  symptoms 
in  these  cases  are  due  to  principles  taken  into  the  blood  from  the  wasting 
thyroid  body.  The  second  form  of  iodism  of  Rilliet,  in  which  the  ner- 
vous symptoms  are  prominent,  has  been  spoken  of  by  other  authorities  ; 
and  Brodie  has  especially  noted  disturbances  of  vision  and  paralysis.  In 
some  rare  cases  neuralgic  pains  and  other  disturbances  of  nerve-functions 
have  occurred,  indicating  that  iodine  is  capable  of  causing  a  peripheral 
neuritis.* 

The  most  common  symptoms  of  iodism,  as  seen  in  the  United  States 
in  non-goitrous  individuals,  are  dull  pain  in  the  region  of  the  frontal  sinus, 
coryza,  sore  throat,  ptyalism,  and  an  eruption  upon  the  skin,  which  is 
usually  an  acne,  but  may  take  almost  any  shape.  In  its  serious  forms  it 
becomes  pustular  or  bulla-like,  and  may  be  accompanied  by  much  der- 
matitis, ulceration,  and  even  very  violent  constitutional  disturbances.  A 
remarkable  iodic  dermatitis  tuberosa  has  been  noted  by  Besnier,  Duhr- 
ing,  and  R.  W.  Taylor. f  In  rare  cases  there  is  an  excessive  suscepti- 
bility to  iodine,  often  accompanied  by  marked  irregularity  of  the  iodic 
symptoms.  Thus,  we  have  seen  six  grains  of  potassium  iodide  given  in 
daily  dose  repeatedly  provoke  in  a  man  violent  conjunctivitis  with  oedema 
around  the  eye,  beginning  unilaterally,  but  involving  the  whole  face  in  a 
violent  erythema  with  great  subdermal  exudation.  Iodic  accidents  are 
especially  apt  to  be  severe  when  there  is  kidney  disease,  as  in  a  case  re- 
ported by  F.  Wolf,11  in  which  forty  grains  of  potassium  iodide  given  in 
two  days  appear  to  have  produced  death.  \  It  is  further  possible  that 
iodic  accidents  may  depend  upon  gastric  conditions,  since  Bjelogolowy 81 
believes  that  his  researches  have  shown  that  when  the  contents  of  the 
stomach  have  a  heightened  acidity  and  contain  the  nitrites,  iodine  is  set 
free  in  the  stomach  from  the  iodides  and  produces  abnormal  effects. 

Most  authorities  affirm  that  iodine  and  potassium  iodide  produce  sim- 
ilar symptoms.  S6e,  indeed,  asserts  that  iodine  exists  in  the  blood  only 
in  the  form  of  an  alkaline  iodide,  while  H.  Kammerer 12  and  Binz  believe 
that  the  iodides  are  decomposed  in  the  tissues  and  act  by  the  liberation 
of  the  iodine.  §  We  do  not  think,  however,  that  these  views  can  be  ac- 
cepted as  established,  and  the  general  professional  belief  is  that  the  thera- 
peutic value,  and  consequently  the  physiological  action,  of  iodine  and 

*  See  Therapeut.  Monatshefte,  1888,  iii. 

t  See  New  York  Med.  Journ.,  November,  1888. 

J  See  also  Journ.  Cutan.  and  Vener.  Dis.,  iv. ;  Miinchener  Med.  Wochenschr., 
xxxiii.  and  xxxiv. 

g  Consult  also  Bucheim  (Arch.  f.  Exper.  Path.  u.  Pharm.,  iii.).  Dubujadoux  (Gaz. 
Hebd.,  1883,  xx.  24)  found  that  iodine  injected  into  guinea-pigs  suffering  from  malignant 
pustule  has  no  influence  upon  the  disease,  even  if  the  injections  be  repeated  until  they 
kill  the  animal,  and  that  the  blood  also  is  as  poisonous  as  ever  to  other  guinea-pigs.  This 
led  him  to  believe  that  the  iodine  exists  in  the  blood  in  a  new  compound  which  is  not 
antiseptic.  He  believes  this  compound  to  be  albuminous,  because  he  has  found  that 
iodine  mixed  with  milk  or  albuminous  solutions  soon  disappears,  so  that  it  cannot  be 
recognized  by  the  starch  test,  and  that  shortly  after  this  disappearance  putrefaction 
sets  in. 


502  GENERAL  REMEDIES. 

potassium  iodide  are  different.  Iodine  is  universally  preferred  in  scrofu- 
losis,  the  iodide  in  rheumatism.  We  have  given  the  salt  in  enormous 
doses,  and  have  seen  nervous  symptoms  in  only  a  single  case, — a  man 
who  received  for  a  long  time  two  hundred  and  seventy  grains  a  day,  and 
who  was  intensely  sleepy  and  stupid,  presenting  symptoms  exactly  similar 
to  those  of  bromism,  including  an  eruption  of  acne.  Potassium  iodide 
is  said  sometimes  to  produce  sudden  oedema  of  the  glottis,  accompanied 
by  excessive  dyspnoea,  and  ending,  unless  tracheotomy  be  performed,  in 
death.* 

The  action  of  iodine  upon  the  circulation  has  been  studied  by  various 
experimenters  with  such  alleged  contradictory  results  that  at  present  the 
most  probable  conclusion  is  that  in  moderate  amounts  iodine  has  little 
direct  influence  upon  the  circulation. 

Rose 1S  believed  that  the  iodide  produced  a  vascular  spasm,  but  most  subse- 
quent observers  have  asserted  that  dilatation  of  the  small  vessels  takes  place,  and 
Se"e  and  Lapicque  u  believe  that  the  potassium  iodide  acts  like  digitalis  upon  the 
heart,  but  that  it  also  dilates  the  vessels,  and  in  this  way  relieves  aneurism.f 

M.  von  Zeissl 15  asserted  that  the  injection  of  the  solution  of  iodine  in  sodium 
iodide  into  the  jugular  vein  produces  a  temporary  increase  of  pressure  in  the  left 
auricle,  with  elevation  of  the  pressure  in  the  pulmonary  arteries  and  pulmonic 
oedema,  the  latter  phenomenon  being  due  to  narrowing  of  the  vessels  by  a  direct 
influence  of  the  iodine  upon  their  walls.  He  further  affirms 16  that  the  injection  of 
the  iodine-iodide  solution  into  the  distal  end  of  the  carotid  causes  an  increase  of  the 
general  blood-pressure,  but  a  much  greater  increase  of  the  intra-cerebral  pressure, 
the  result  of  an  cedematous  exudation. 

On  the  other  hand,  Prevost  and  Binet "  have  come  to  the  conclusion,  with  ap- 
parent correctness,  that  watery  iodic  solutions  slowly  injected  into  the  veins  have 
no  effect  upon  the  circulation  unless  in  overwhelming  amount ;  nevertheless,  the 
potassium  iodide  injected  into  the  veins  when  in  very  feeble  dose  causes  temporary 
rise,  but  when  in  large  dose  marked  depression  of  the  arterial  pressure. 

Action  on  Kidneys,  and  Excretion. — During  its  passage  through  the 
kidneys  iodine  undoubtedly  exerts  an  influence  upon  those  organs,  as  is 
shown  by  its  producing  albuminuria  at  times.  It  is  indeed  asserted  that 
it  occasionally  causes  a  true  tubular  nephritis.  The  evidence  as  to  its 
effect  upon  the  solids  of  the  urine  is  both  contradictory  and  insufficient. 

M.  Rabuteau  (quoted  by  Se"e)  dieted  himself  for  five  days,  measured  the 
quantity  of  urea  daily  eliminated,  took  iodine  on  the  fifth  day,  and  found  a  decided 
decrease  in  the  excretion  of  urea.  It  is  plain  that  this  experimentation  was  too 
slight  to  be  of  much  value,  and  Hermann  von  Boeck 18  found  that  the  ingestion  of 
iodine  does  not  increase  notably  the  elimination  by  the  kidneys  or  bowels.  On  the 
other  hand,  M.  Bouchard  (quoted  by  Se'e)  declares  on  his  personal  experience  that 
iodine  does  increase  the  daily  elimination  of  urea,  especially  in  diabetic  patients.  C. 
Handfield  Jones 19  analyzed  the  urine  of  six  patients  taking  large  doses  of  potassium 
iodide,  with  the  following  results  :  first,  water  increased  in  three  cases  very  much, 
in  one  slightly  so,  in  two  diminished  ;  second,  acidity  increased  in  three  and  dimin- 
ished in  two  ;  third,  urea  increased  in  three  and  diminished  in  three  ;  fourth,  phos- 

*  Nine  cases,  A.  Groenouw  (  Therap.  Monatshefte ,  1890). 
f  See  also  Pierrot  {Nancy  Thesis,  1890,  310). 


ALTERATIVES.  503 

phoric  acid  and  sulphuric  acid  increased  in  four  and  diminished  in  two  ;  fifth,  chlo- 
rine increased  very  greatly  in  two  cases,  moderately  in  one,  and  decreased  in  two  ; 
sixth,  uric  acid  increased  very  greatly  in  two  cases  and  diminished  in  four.  Eugene 
I.  Duchesne  M  found  that  potassium  iodide  and  tincture  of  iodine  notably  increased 
the  elimination  of  urea,  while  sodium  iodide  was  followed  by  a  distinct  decrease 
of  this  excretion.  All  the  preparations  of  iodine  used  increased  the  elimination 
of  uric  acid.  ^lenrijean  and  Corin 21  find  that  almost  all  of  the  iodides  markedly 
increase  the  elimination  of  nitrogen  as  well  as  of  the  phosphates  and  chlorides.  On 
the  other  hand,  A.  Haig  M  affirms  that  the  iodides  have  a  marked  effect  in  lessening 
the  elimination  of  uric  acid  and  the  urates,  and  as  a  result  of  this  diminish  the 
arterial  tension. 

THERAPEUTICS. — As  an  alterative,  iodine  is  of  especial  value  in  chronic 
scrofula.  In  those  cases  in  which  there  is  indolent  enlargement  of  the 
lymphatics,  which  exhibit  no  tendency,  or  but  little  tendency,  to  sup- 
purate, it  is  of  especial  value.  Except  in  very  acute  cases,  however,  it 
should  always  be  tried,  even  when  the  glands  do  tend  towards  suppura- 
tion, especially  as  it  exerts  a  very  beneficial  influence  upon  the  ulcers 
left  after  suppuration.  In  other  forms  of  scrofulous  disease,  in  chronic 
enlargements  of  the  joints,  and  bone  affections  of  such  nature,  iodine  is 
often  of  great  service.  As  scrofulosis  is  generally,  if  not  always,  associ- 
ated with  lowered  nutrition  and  with  anaemia,  cod-liver  oil  and  iron  in 
some  form  should  usually  be  administered  as  adjuvants.  At  the  same 
time  that  the  drug  is  exhibited  internally  in  these  cases,  its  ointment 
should  be  freely  applied  to  the  enlarged  and  indurated  glands.  Expe- 
rience has  demonstrated  the  value  of  iodine  in  true  goitre.  All  tumors 
of  the  thyroid  body  are  not  goitre,  however  ;  cystic  degeneration  of  it  is 
very  common,  and  is  in  no  wise  benefited  by  iodine.  It  is  in  simple 
hypertrophy  of  the  gland  that  iodine  used  internally  and  applied  exter- 
nally over  the  tumor  is  beneficial.  During  the  acute  stage  of  enlarge- 
ment the  use  of  leeches  is  often  of  great  benefit,  and  whenever  much 
tenderness  exists  should  precede  the  exhibition  of  the  drug.  In  phthisis 
iodine  sometimes  does  good,  but  only  in  the  most  chronic  cases  ;  and  in- 
halations of  its  vapors,  as  have  been  recommended  by  Piorry,  can  be  of 
service  only  by  stimulating  the  bronchial  mucous  membrane  and  the  sur- 
faces of  cavities.  When  softening  is  progressing  and  the  lung  breaking 
down,  iodine  appears  to  hasten  the  process. 

Local  Application. — As  a  simple  counter-irritant,  iodine  is  very  fre- 
quently employed  when  it  is  desired  to  maintain  a  mild,  persistent  influ- 
ence, as  in  chronic  rheumatic  affections  and  sometimes  in  phthisis.  For 
this  purpose  the  tincture  is  generally  preferred,  and  it  should  be  applied 
freely  once  or  twice  a  day,  or  every  other  day,  according  to  the  suscepti- 
bility of  the  patient's  skin.  In  various  affections  of  the  skin  iodine  has 
been  employed  with  asserted  advantage.  In  erysipelas  of  the  skin  very 
beneficial  results  have  been  ascribed  to  its  local  use,  but  great  care  is 
necessary  lest  it  be  applied  too  strong.  We  have  seen  very  serious 
results  from  the  destruction  by  it  of  the  skin  in  this  affection.  If  the  full 
strength  of  the  tincture  be  used,  it  should  be  applied  at  first  very  lightly, 


5o4  GENERAL  REMEDIES. 

and  not  more  than  once  in  the  twenty-four  hours.  In  psoriasis,  in  acne, 
and  in  parasitic  skin  diseases  it  has  been  used,  but  holds  only  a  second  rank 
among  remedies.  In  a  similar  manner  it  is  employed  in  various  chronic 
diseases  of  the  mucous  membranes,  such  as  ozczna,  leucorrkcea,  chronic 
cystitis,  chronic  dysentery,  and  scrofulous  ophthalmia, — whenever,  in  a 
word,  an  alterative,  stimulant  action  is  desired.  In  cases  of  retraction  of 
the  gums,  with  consequent  loosening  of  the  teeth,  Stille"  recommends  the 
application,  with  a  camel'  s-hair  brush,  after  each  meal,  of  a  watery  solu- 
tion (one  grain  to  a  fluidounce)  of  iodine,  the  mouth  being  immediately 
afterwards  washed.  The  most  important  external  use  of  iodine  is  as  a 
resolvent  in  cases  of  indolent  glandular  hypertrophic  enlargement,  and 
where  there  are  large  watery  exudations,  as  in  some  forms  of  chronic 
pleurisy  and  of  diseased  joints. 

Iodine  has  been  very  largely  employed  by  injection  into  serous  cysts, 
as  in  hydrocele,  for  the  purpose  of  exciting  inflammation  and  causing 
obliteration  of  their  cavity  ;  but  this  use  of  it  is  purely  surgical,  and  the 
reader  is  referred  to  treatises  upon  such  subjects.  In  chronic  empyema 
the  injection  of  iodine  after  free  exit  has  been  given  to  the  pus  is  often  of 
the  greatest  service.  The  solution  in  the  beginning  should  be  very  weak, 
containing  not  more  than  six  grains  each  of  iodine  and  of  potassium 
iodide  in  a  pint  of  water  ;  with  this  the  pleura  should  be  daily  washed 
out,  the  strength  of  the  solution  being  gradually  increased. 

ADMINISTRATION. — Iodine  is  never  administered  in  solid  form  ;  nor 
should  the  tincture  be  given  internally,  because  the  iodine  is  precipitated 
by  the  watery  juices  of  the  stomach. 

The  only  preparation  of  iodine  for  internal  use  is  LIQUOR  IODI  COM- 
POSITUS — Compound  Solution  of  Iodine  —  Lugoi 's  Solution,  U.  S. 
(Iodine,  five  per  cent. ;  Potassium  iodide,  ten  per  cent.).  As  the  potas- 
sium iodide  holds  the  iodine  in  solution,  this  preparation  may  be  freely 
diluted  without  precipitation,  and  may  even  be  used  hypodermically,  as 
suggested  by  Da  Costa,"  in  glandular  enlargements.  The  U.  S.  Phar- 
macopoeia dose  is  five  to  ten  drops  (0.3-0.6  C.c. ),  well  diluted. 

For  external  use  there  are  a  tincture  (TINCTURA  IODI — seven  per 
cent.,  U.  S. )  and  an  ointment  (UNGUENTUM  IODI  :  Iodine,  four  parts  ; 
Potassium  iodide,  four  parts;  to  one  hundred,  U.  S. ). 

Iodine  has  been  used  hypodermically,  but  usually  produces  so  much 
local  irritation  as  to  forbid  its  employment.  According  to  A.  O.  Squier," 
the  following  may  be  injected  almost  without  causing  pain. 

Eucalyptol,  thirty-two  minims  ;  Guaiacol,  pure,  sixteen  minims ;  lodoform, 
eight  grains ;  Iodine,  four  grains ;  Oil  of  sweet  almonds,  sterilized,  sufficient  to 
make  one  ounce.  Dose,  ten  to  thirty  minims,  hypodermically. 

SYRUPUS  ACIDI  HYDRIODICI.  U.  S. — Syrup  of  Hydriodic  Acid  is  a 
syrupy  solution,  containing  about  one  per  cent,  by  weight  of  absolute 
hydriodic  acid.  For  practical  purposes  hydriodic  acid  may  be  considered 


ALTERATIVES.  505 

as  pure  iodine  ;  so  that  sixty  grains  (teaspoonful)  of  the  official  syrup 
contain  practically  six-tenths  of  a  grain  of  iodine,  and  are  therefore  equal 
to  a  little  over  one  grain  of  potassium  iodide.  The  syrup  is  transparent, 
odorless,  and  has  a  sweet,  somewhat  acidulous — to  most  persons  inde- 
scribable— taste.  As  a  simple  alterative  in  non-syphilitic  cases,  from  one 
to  two  fluidrachms  (4—7  C.  c. )  may  be  administered,  well  diluted  ;  in  the 
treatment  of  syphilis  it  is  too  weak  to  be  relied  upon. 

POTASSII   IODIDUM— POTASSIUM    IODIDE.     U.S. 

This  salt  occurs  in  white  or  colorless,  generally  cubic,  crystals,  solu- 
ble in  0.75  part  of  water  and  in  eighteen  parts  of  alcohol.  If  to  its  solu- 
tion starch  be  added,  no  blue  color  should  arise,  but  on  the  passage  of 
chlorine  the  characteristic  iodine  reaction  should  take  place,  owing  to  the 
liberation  of  the  metalloid  by  the  gas  ;  or  if  sulphuric  acid  be  added,  a 
purple  tint  gradually  appears,  and  deepens  into  blue  :  a  spontaneous  blue 
color  betrays  the  presence  of  the  potassium  iodate,  a  harmful  adulteration. 
At  a  dull  red  heat  potassium  iodide  fuses  into  a  crystalline  mass  ;  by  a 
bright  heat  it  is  decomposed. 

PHYSIOLOGICAL  ACTION. — Absorption  and  Elimination. — Potassium 
iodide  is  rapidly  absorbed,  and  eliminated  with  fair  promptness.  According 
to  Anten 27  it  requires  forty  hours  for  the  complete  elimination  of  a  single 
dose  of  the  salt,  about  seventy-five  per  cent,  escaping  through  the  kid- 
neys. This  author  has  shown  that  the  presence  of  mucilaginous  substances 
interfere  with  its  absorption,  whereas  if  potassium  nitrate  or  sodium  chloride 
be  administered  the  iodide  appears  more  promptly  in  the  urine.  Lesser  w 
has  sho\vn  that  it  circulates  as  an  alkaline  iodide  and  is  eliminated  unchanged, 
about  one-half  of  the  amount  in  the  blood  being  dissolved  in  the  serum 
and  the  remaining  portion  carried  by  the  red  blood-corpuscles.  The  per- 
centage of  iodine  he  found  to  be  practically  the  same  in  all  the  organs  of 
the  body  after  the  internal  administration  of  potassium  iodide,  showing  that 
there  is  no  storage  of  the  drug  in  any  particular  organ.  Potassium  iodide 
influences  nutrition  in  a  manner  similar  to  iodine  :  indeed,  most  authori- 
ties teach  that  their  action  is  identical  ;  yet  in  therapeutics  they  find  a 
different  range  of  employment.  I.  Wallace 25  has  found  that  the  iodide 
lessens  the  elimination  of  lime  salts  through  the  kidneys  ;  but  his  analyses 
were  not  sufficiently  repeated  to  prove  that  this  is  a  constant  effect.*  The 
theory  that  potassium  iodide  does  good  in  aneurism  by  dilating  the  blood- 
vessels has  been  shown  to  be  untrue  by  Stockman  and  Charteris,29  who 
found  that  it  had  no  effect  on  the  circulation  unless  given  in  large  enough 
dose  to  call  forth  the  depressant  action  of  the  base. 

THERAPEUTICS. — In  certain  forms  of  rheumatism  potassium  iodide 
is  of  value.  In  the  early,  active  stages  of  inflammatory  rheumatism. 

*'For  a  research  upon  the  physiological  action  of  large  amounts  of  potassium  iodide 
injected  into  the  blood,  see  Arbeilen  aus  dem  Pharmak.  Laborator.  zu  Moskau,  i.  125. 
As  it  does  not  seem  to  throw  light  upon  the  therapeutic  use  of  the  drug,  it  is  not  here 
analyzed. 


5o6  GENERAL  REMEDIES. 

it  is  useless  ;  but  later,  when  the  joint  symptoms  persist  in  a  subacute 
form,  the  iodide  comes  very  well  into  play.  In  subacute  or  muscular  rheu- 
matism the  iodide  is  an  efficient  remedy.  Often  when  the  symptoms  are 
very  acute  it  may  advantageously  be  combined  with  the  alkalies,  and  in 
lingering  cases,  especially  where  there  is  reason  to  suspect  a  gouty  taint, 
with  colchicum.  In  sciatica,  in  lumbago,  and  in  rheumatic  neuralgia  fol- 
lowing exposure  to  cold  or  wet,  as  in  all  other  forms  of  subacute  rheuma- 
tism, much  is  to  be  hoped  for  from  its  use.  In  gout  it  is  of  less  service 
than  in  rheumatism,  but  in  the  chronic  form  of  the  disease,  and  in  the 
irregular,  inherited  gout  which  so  frequently  appears  as  neuralgia  or  other 
anomalous  affection,  it  adds  to  the  efficiency  of  small  continuous  doses  of 
colchicum.  In  rheumatic  gout,  or  rheumatoid  arthritis,  it  should  be 
tried,  although  little  is  to  be  hoped  for  from  its  use.  There  is  a  good 
deal  of  clinical  testimony  as  to  the  value  of  potassium  iodide  given  con- 
tinuously between  the  paroxysms  of  asthma.  This  disorder  appears  at 
times  to  bear  a  close  relation  to  irregular  gout  or  rheumatism,  and  it  is 
probably  under  these  circumstances  that  the  remedy  is  efficient.  In 
tertiary  syphilis,  including  in  the  term  all  cases  of  syphilitic  bone,  visceral, 
or  nervous  disease,  the  remedy  is  really  of  inestimable  value.  It  must 
be  given  freely,  and,  when  there  is  no  cachexia,  may  be  advantageously 
combined  with  the  mercury  bichloride.  It  is  scarcely  in  place  here  to 
enumerate  all  the  forms  which  tertiary  syphilis  may  assume  ;  but  the 
iodide  is  useful  wherever  the  dyscrasia  has  existed  for  a  length  of  time.* 
Recently  potassium  iodide  has  been  largely  employed  in  the  treatment  of 
actinomycosis,  and  seems  to  exercise  in  this  disease  a  specific  action. 

Potassium  iodide  appears  to  have  the  power  of  promoting  absorption 
of  serous  fluids,  and  certainly  is  of  value  in  chronic pleuritis  with  effusion, 
in  chronic  pericarditis,  and  even  in  chronic  hydrocephalus. 

In  aortic  aneurism  large  doses  of  potassium  iodide  with  continuous 
rest  in  the  horizontal  position  are  much  used. 

In  various  chronic  metallic  poisonings  the  potassium  iodide  is  of  great 
service.  With  both  lead  and  mercury  it  forms  double  salts,  which  are 
soluble,  and  there  is  very  good  reason  for  believing  that  the  formation  of 
these  salts  takes  place  in  the  economy,  and  that  the  metal  which  has  been 
lying  in  an  insoluble  condition  in  the  various  tissues  is  taken  up  and  ex- 
creted. Severe  salivation  and  ulcerative  stomatitis  have  sometimes  re- 
sulted from  the  use  of  the  potassium  salt  in  those  who  had  previously 
taken  large  quantities  of  mercury  ;  f  and  in  Melsen'  s  experiments,  dogs 
to  which  insoluble  preparations  of  mercury  had  previously  been  given 
without  the  induction  of  severe  symptoms  afterwards  died  under  the 
action  of  the  iodide,  the  mercury  also  having  appeared  in  their  urine. 
The  experiments  of  Mayenjon  and  Bergeret  (quoted  in  the  article  on 
Mercury)  afford  striking  confirmation  of  these  facts,  and  seem  to  render 

*  For  complete  literature  on  this  subject,  see  Lieblein,  B.  K.  €.,  1900,  xxviii.  198. 
t  See  Budd  (Brit,  and  For.  Medico-Chir.  Rev.,  xi.  202)  for  a  striking  case. 


ALTERATIVES.  507 

the  evidence  irresistible  that  the  iodide  does  bring  about  the  elimination  of 
mercury.  In  regard  to  lead,  the  researches  of  Parkes,  Goolden,  Swift, 
Melherbe,  Sieveking,*  and  Marshall  w  have  shown  that  very  frequently 
in  cases  of  chronic  lead-poisoning  the  exhibition  of  potassium  iodide 
causes  the  appearance  of  lead  in  the  urine.  This  chemical  evidence  is 
abundantly  corroborated  by  clinical  experience,  so  that  in  all  cases  of 
chronic  metallic -poisoning  the  persistent  use  of  potassium  iodide  should 
be  tried. 

ADMINISTRATION*. — The  ordinary  dose  is  ten  grains  (0.6  Gm. )  three 
times  a  day,  but  much  larger  quantities  may  often  be  given  with  impunity, 
and  in  internal  syphilitic  affections  may  be  necessary.  In  the  latter  class 
of  diseases  the  best  plan  is  to  begin  with  twenty  grains  (1.3  Gm. )  three 
times  a  day,  and  rapidly  increase  the  amount  until  drachm  doses  are 
reached,  or  frontal  pain  or  other  symptom  of  iodism  appear.  BesnierM 
recommends  the  injection  of  the  iodides  directly  into  the  centre  of  gumma 
for  syphilitic  patients  who  show  an  intolerance  towards  the  remedy.  The 
best  substance  for  disguising  the  very  disagreeable  taste  of  the  drug  is  the 
compound  syrup  of  sarsaparilla.  UNGUENTUM  POTASSII  IODIDI,  U.  S. , 
contains  ten  per  cent,  of  the  iodide. 

LIQUOR  ARSENI  ET  HYDRARGYRI  IODIDI.  U.  S. — Solution  of  Arsenic 
and  Mercuric  Iodide  contains  one  per  cent,  each  of  the  arsenic  iodide 
and  the  red  mercury  iodide.  It  was  originally  suggested  by  a  surgeon 
of  Dublin,  by  whose  name  it  is  very  generally  known.  Donovan' s  Solu- 
tion is  a  powerful  alterative,  used  chiefly  in  very  obstinate  chronic  scaly 
skin  diseases,  when  the  local  action  is  of  a  very  low  grade,  and  in  chronic 
rheumatism.  It  is  an  exceedingly  active  preparation,  very  capable  of 
acting  as  a  corrosive  poison,  and  when  administered  a  little  too  freely  is 
said  sometimes  to  cause  salivation.  When  applied  locally,  it  acts  as  a 
violent  irritant.  The  dose  is  from  three  to  ten  drops  (0.2-0.6  C.c. ),  well 
diluted. 

AMMONII   IODIDUM— AMMONIUM   IODIDE.    U.S. 

Ammonium  iodide  occurs  in  minute,  colorless,  cubical  crystals,  or  as 
a  white  granular  powder,  hygroscopic,  without  odor  when  colorless,  on 
exposure  becoming  yellowish,  and  emitting  a  slight  odor  of  iodine,  and 
having  a  sharp  saline  taste.  Ammonium  iodide  resembles  closely,  in  its 
action,  iodine  and  potassium  iodide,  and  has  been  employed,  both  exter- 
nally and  internally,  as  a  resolvent  in  secondary  syphilis,  chronic  rheuma- 
tism, incipient  phthisis,  and  in  a  variety  of  forms  of  scrofulous  disorder 
with  glandular  enlargements.  The  ointment  (one-half  to  one  drachm 
to  an  ounce)  has  been  used  in  lepra,  psoriasis,  scrofulous  glands,  etc. 
As  the  iodide  is  decomposed  by  the  air,  the  ointment  should  be  kept 
in  well-stopped  bottles.  For  internal  use  the  dose  of  ammonium  iodide 
is  from  three  to  ten  grains  (o.  2-0. 6  Gm. ) ,  in  dilute  solution. 

*  See  Stille's  Therapeutics,  ii.  735,  Blanchard  &  Lea,  1864. 


5o8  GENERAL  REMEDIES. 

STRONTII    IODIDUM— STRONTIUM    IODIDE.     U.  S. 

Strontium  iodide  occurs  in  colorless,  transparent,  hexagonal  plates, 
odorless,  and  having  a  bitterish,  saline  taste.  It  is  deliquescent,  and  on 
exposure  to  air  and  light  becomes  yellow.  It  is  soluble  in  0.6  part  of 
water  at  15°  C.  (59°  F. )  and  in  0.27  part  of  boiling  water.  This  salt 
has  been  brought  forward  as  a  means  of  obtaining  the  alterative  influence 
of  an  iodide  without  causing  irritation  of  the  intestinal  tract  or  depression 
of  the  general  nutrition.  It  contains  about  56.5  per  cent,  of  iodine,  and, 
although  its  actual  value  has  scarcely  as  yet  been  made  out,  may  be  sub- 
stituted for  potassium  iodide  in  various  diseases.  The  dose  is  from  five 
to  ten  grains  (0.3-0.6  Gm. ),  increased  pro  re  nata.  It  is  best  adminis- 
tered in  solution. 

IODIPIN. — This  is  a  yellow,  oily  fluid,  said  to  be  an  iodine  addition-product  of 
sesame  oil,  containing  ten  per  cent,  of  iodine  in  chemical  combination.  According 
to  H.  Winternitz,1  iodipin  when  taken  internally  passes  unchanged  into  the  intes- 
tines, where  it  is  slowly  digested  with  an  absorption  of  iodine,  probably  as  an 
alkaline  iodide  ;  and  the  final  escape  from  the  intestines  of  a  portion  of  the  iodipin 
unchanged.  When  it  is  injected  hypodermically  it  forms  a  local  depot,  as  it  were, 
from  which  the  iodine  is  very  slowly,  but  continuously,  absorbed.  Under  these  cir- 
cumstances it  is  said  to  produce  no  local  disagreeable  symptoms.  Winternitz  affirms 
that  no  absorption  of  iodine  takes  place  after  iodipin  inunction  or  enemata.  In 
chronic  syphilis  it  has  been  used  internally  in  doses  of  from  fifteen  to  thirty  grains 
( 1-2  Gm. )  of  the  ten  per  cent,  iodipin,  which  may  be  injected  daily,  as  recommended 
by  Schuster.2  Naegeli3  recommends  for  the  purpose  of  producing  local  absorption 
subconjunctival  injections  of  one-third  to  one-half  minim  (0.02-0.3  C.c. )  of  iodipin 
in  specific  retinitis,  scleritis,  keratitis  dendritica,  and  keratitis  neuroparalytica. 
Dose  of  iodipin,  one  to  two  drachms,  given  in  emulsion,  three  or  four  times  a  day. 

ACIDUM  HYDRIODICUM  DILUTUM.  U.  S. — Dilute  hydriodic  acid  is 
a  ten  per  cent,  solution  in  water  of  absolute  hydriodic  acid.  Owing  to  its 
ready  decomposition  by  light,  the  U.  S.  Pharmacopoeia  directs  that  it 
should  be  kept  in  amber-colored  bottles.  When  given  internally  it  is 
capable  of  producing  the  alterative  effects  of  iodine,  but  is  scarcely  an 
advantageous  preparation.  Dose,  fifteen  to  twenty  minims  ( i-i.  33  C.  c. ), 
well  diluted. 

IODOFORMUM— IODOFORM.     U.S. 

This  substance  was  discovered  by  Se"rullas  in  1822,  and  was  intro- 
duced as  a  remedy  by  Glover  in  1837,  but  did  not  become  official  until 
the  1880  revision  of  the  U.  S.  Pharmacopoeia.  It  occurs  as  small,  pearly- 
yellow  crystals,  having  a  strong,  persistent,  saffron-like  odor,  insoluble  in 
water,  but  readily  soluble  in  alcohol  and  in  ether. 

Local  Action. — In  itself  iodoform  is  a  non-irritant,  slightly  desiccant 
powder,  which  appears  to  be  imbued  with  local  anaesthetic  properties, 
so  that  the  rectum  may  be  so  benumbed  by  a  suppository  containing 
iodoform  that  defecation  may  take  place  without  the  knowledge  of  the 
individual.  By  decomposition  and  formation  of  new  compounds  iodo- 
form becomes  a  locally  active  substance.  (See  page  512.) 


ALTERATIVES.  509 

Absorption  and  Elimination. — lodoform, — i.e. ,  the  products  of  its  de- 
composition,— is  absorbed  very  slowly  by  the  alimentary  canal,  but  in 
wounds  it  is  taken  up  with  comparative  freedom.  Zeller *  believes  that 
there  is  always  an  albuminous  compound  of  iodine  formed  at  the  seat  of 
absorption.  The  iodine  escapes  from  the  body  by  all  the  secretions  as 
well  as  by  the  breath,  partially  as  an  iodide,  partially  as  an  iodate,  and 
partially  in  the  form  of  a  new  organic  compound  of  iodine.*  According 
to  the  researches  of  Rummo,  the  elimination  of  iodine  commences 
within  one  hour  after  the  stomachic  ingestion  of  the  iodoform,  and  goes 
on  so  slowly  that  the  haloid  can  be  found  in  the  urine  three  days  later. 

General  Effects. — In  the  largest  therapeutic  doses  (five  to  six  grains) 
iodoform  produces  no  symptoms,  and  we  know  of  no  cases  of  poisoning 
by  its  internal  administration.  On  the  other  hand,  its  surgical  use  has  led 
to  a  number  of  fatal  poisonings.  The  symptoms,  as  recorded,  have  been 
very  various.  They  may  be  preceded  by  general  malaise  for  a  day,  and 
then  suddenly  burst  forth. f  In  the  most  characteristic  and  severe  class 
of  cases  the  phenomena  resemble  somewhat  those  of  meningitis,  and  may 
be  somnolence,  deepening  into  stupor,  with  contracted,  motionless  pupils, 
or  restlessness,  ending  in  active  delirium,  in  either  case  the  temperature 
being  normal  and  the  pulse  exceedingly  rapid.  A  peculiarity  of  these 
cases  seems  to  be  that  death  usually  follows,  although  the  symptoms  have 
developed  abruptly  and  the  dressings  have  been  removed  at  once.  Schede, 
of  Hamburg,  describes  six  classes  of  cases,  his  sixth  form  being  that  just 
spoken  of.  i.  High  fever,  without  other  phenomena.  2.  Fever,  with 
mild  gastro-intestinal  irritation,  depression  of  spirits,  and  rapid  pulse  ; 
recovery  almost  invariable.  3.  Very  rapid,  soft  pulse,  150  to  180,  no  fever ; 
great  danger.  4.  Very  rapid  pulse,  with  high  fever  ;  death  almost  in- 
variable. 5.  After  severe  operations,  rapid  collapse  and  death.  A  form 
of  poisoning  with  melancholia,  dilated  pupils,  and  hallucinations  is  also 
described.  A  roseola-like  dark  red  eruption  has  been  noted  in  some 
cases  of  poisoning  (Anschutz  has  seen  violent  acne)  ;  even  when  the  con- 
stitutional symptoms  are  very  slight  there  may  be  an  extensive  erythema.  \ 
Convalescence  may  be  very  protracted,  the  patient  remaining  in  a  con- 
dition of  unconsciousness  or  semi-consciousness  for  some  days,  with 
complete  loss  of  memory  and  some  evidences  of  mental  disturbance. 
According  to  De  Schweinitz,  iodoform  has  rarely  produced  amaurosis  or 
amblyopia  with  scotomata. 

On  account  of  the  indefiniteness  of  the  symptoms  of  iodoform-poi- 
soning  great  importance  attaches  to  any  positive  means  of  recognizing 
the  nature  of  the  illness.  Burlureaux  affirms  that  if  a  piece  of  silver 

*  For  an  important  bibliography,  see  the  paper  of  M.  Rummo.  For  details  as  to 
elimination  and  discussion  of  methods  of  finding  the  iodine  in  the  urine,  consult  Johannes 
Grundler  (Schmidt's  Jahrb.,  ccii.  232),  Harnack  (Berlin.  Klin.  Wochenschr.,  1883,  No. 
47;  also  Zeits.  f.  Physiol.  Chem.,  1884,  viii.  158).  A.  Zeller  (Arch.  f.  Klin.  Chir.,  xxviii. 
590),  and  E.  Baumann  (Schmidt's  Jahrb.,  ccii.  233  ;  Verhandl.  Deutsch.  Gesell.  f.  Oiemie, 
Berlin,  1882,  xi.  219). 

fCase,  Deutsch.  Med.  Wochenschr.,  ix.,  443. 

t  Cases,  Intern.  Cong.,  Copenhagen,  1884,  Sect.  Dermatol.,  118. 


5io  GENERAL  REMEDIES. 

be  placed  in  the  mouth  of  a  person  suffering  from  iodoform-intoxication, 
the  taste  of  garlic  will  be  immediately  perceived,  and  that  if  some  of  the 
saliva  be  mixed  with  calomel,  a  canary-yellow  precipitate  of  mercurial 
iodide  will  be  obtained  ;  according  to  Sasse,  if  a  pinch  of  powdered 
calomel  be  placed  upon  a  saucer,  and  a  few  drops  of  the  urine  from  a 
case  of  iodoform-poisoning  be  mixed  with  it  by  means  of  a  glass  rod,  the 
yellow  color  will  appear  (yellow  iodide).  These  tests  prove  only  that 
the  patient  is  under  the  influence  of  some  compound  of  iodine,  but,  if 
correct,  must  in  many  cases  be  sufficient  for  the  purposes  of  the  prac- 
titioner. 

Notwithstanding  numerous  experiments  upon  the  lower  animals,  fur- 
ther research  is  necessary  before  any  positive  knowledge  can  be  reached 
as  to  the  physiological  action  of  iodoform,  although  it  is  probable  that  it 
acts  very  much  as  does  iodine. 


The  symptoms  produced  by  iodoform  in  the  frog  are  said  to  be  muscular  relax- 
ation with  sometimes,  at  a  later  stage,  convulsive  movements.  In  the  higher  ani- 
mals large  but  non-toxic  doses  produce  symptoms  of  intoxication,  tottering,  weak- 
ness, and  loss  of  appetite,  but  no  vomiting  ;  fatal  doses  cause  anaesthesia,  narcosis, 
convulsions,  with  violent  opisthotonos,  hurried  or  irregular  breathing,  slow,  feeble 
pulse,  and  finally  death.  A.  Hdyges 2  found  that  in  dogs  and  cats  toxic  doses 
caused  deep  sleep  without  loss  of  reflex  activity,  but  that  in  rabbits  no  sleep  re- 
sulted. Very  frequently  after  these  large  doses,  especially  when  they  are  repeated, 
there  is  great  gastro-intestinal  disturbance,  as  is  shown  by  vomiting,  diarrhoea,  and 
dysentery,  with  bloody  discharges.  The  action  of  the  drug  upon  the  circula- 
tion has  been  especially  studied  by  Rummo.3  He  finds  that  in  the  frog  the 
rate  of  the  cardiac  pulsations  is  lessened,  and  for  a  time  the  energy  of  the  ventric- 
ular systole  is  increased,  but  afterwards  the  pulsations  become  feeble,  and  finally 
the  heart  is  arrested  in  diastole  ;  the  contractions  cannot  be  re-established  by  the 
use  of  atropine.  In  the  mammal  the  rate  of  the  pulse  is  decreased,  and  after 
small  doses  the  arterial  pressure  is  at  first  increased.  By  large  doses  the  press- 
ure is  much  diminished.  Section  of  the  pneumogastrics  does  not  affect  the  car- 
diac action  of  the  drug.  After  very  large  doses  there  are  albuminuria  and  even 
haematuria. 


These  various  researches  would  indicate  that  the  iodic  compounds 
liberated  by  iodoform  are  universal  poisons,  and  that  the  conclusion  of 
Rummo  is  corrrect, — namely,  that  iodoform  acts  upon  almost  all  the 
tissues,  but  primarily  upon  the  nerve-centres  and  subsequently  upon  the 
nerve-trunks  and  on  the  muscles. 

After  death  from  iodoform  a  very  wide-spread  fatty  degeneration  is  to 
be  found.  This  change  appears  to  commence  in  the  liver  and  rapidly  ta 
involve  all  tissues  of  the  body.  Floucaud 4  states  that  there  is  a  very 
distinct  alteration  of  the  blood-corpuscles. 

THERAPEUTICS. — At  one  time  iodoform  was  used  to  a  considerable 
extent  as  an  internal  alterative  and  analgesic  in  chronic  syphilis,  espe- 
cially when  there  were  severe  rheumatic,  neuralgic,  or  night-pains.  It  has 
also  been  employed  as  an  absorbefacient  substitute  for  iodine  in  various 
lymphatic  tumors  and  serous  effusions.  In  syphilis  various  clinicians  have 


ALTERATIVES.  511 

borne  testimony  to  the  advantageousness  of  its  hypodermic  use,  three  to 
five  grains  a  day.  It  seems  to  have,  however,  no  superiority  over  the 
simpler  iodine  preparations,  and  to  be  much  less  certain  and  definite  in  its 
action,  so  that  its  internal  use  has  passed  completely  out  of  vogue.  On 
the  other  hand,  as  a  local  remedy,  it  has  continuously  asserted  itself  in 
the  face  of  very  numerous  substitutes,  and  is  used  to-day  as  frequently  as 
it  ever  was.  It  is  useful  in  cases  of  painful  ulcers,  even  when  they  are 
cancerous,  serving  to  alleviate  pain  and  to  promote  cicatrization.  At 
first  employed  especially  in  syphilitic  affections,  it  is  now  known  to  act 
equally  well  in  indolent  leg  ulcers,  in  burns*  and  in  other  non-specific 
abrasions,  and  it  is  thought  to  be  not  only  a  local  anaesthetic,  but  also  a 
decided  stimulant  to  nutrition.  Within  the  last  few  years  it  has  been  very 
freely  employed  as  an  antiseptic  dressing  to  wounds,  and  the  testimony  is 
so  strong  that  it  is  difficult  to  avoid  believing  that  it  is  one  of  the  most 
reliable  of  the  antiseptics.  It  is,  however,  affirmed  to  have  no  power  in 
preventing  erysipelas,  and  used  freely  is  very  dangerous  to  the  patients. 
It  is  employed  either  in  the  form  of  powder  dusted  in  the  wound,  or  as 
dressings  saturated  with  it,  the  first  method  being  at  once  the  more  effec- 
tive and  the  more  dangerous. 

The  danger  of  iodoform -poisoning  in  a  surgical  case  varies  not  only 
with  the  amount  of  iodoform  used,  but  also  with  the  form  of  the  iodoform 
and  the  seat  of  the  application.  The  more  finely  powdered  the  iodoform 
the  greater  its  activity,  and  serious  absorption  is  especially  apt  to  take 
place  from  the  peritoneal  surf  aces,  f 

In  1886  Fiirst  described  furuncular  and  eczematous  inflammation  pro- 
duced by  the  contact  of  iodoform  with  the  skin.  Krevet 5  affirms  that 
this  irritation  can  rapidly  be  relieved  by  momentary  applications  of  very 
hot  water  to  the  part. 

The  good  results  which  have  followed  the  surgical  use  of  iodoform 
as  an  antiseptic  dressing  have  led  to  a  series  of  investigations  as  to  its 
action  on  the  lower  organisms,  with  results  which  are  apparently  at 
variance  with  previous  surgical  teachings.  In  November,  1886,  De 
Ruyter  announced  at  a  meeting  of  the  Berlin  Surgical  Society  that  the 
powder  of  iodoform  has  little  or  no  effect  in  preventing  the  development 
of  bacteria,  and  that  when  it  is  mixed  with  rapidly  infective  bacteria,  like 
those  of  anthrax,  it  does  not  sensibly  influence  the  development  of  the 
disease  which  is  caused  by  inoculation  with  the  mixture.  This  has  been 
confirmed  experimentally  by  Kronacher,6  who  employed  the  bacteria  of 

*  Burns,  Treatment  of. — At  a  discussion  of  the  International  Congress  of  Derma- 
tology, in  1889,  the  conclusion  was  reached  that  the  best  treatment  of  burns  in  the  begin- 
ning is  to  cut  the  bullae,  wash  the  part  with  a  very  weak  solution  of  salt,  and  then  dress 
with  iodoform  gauze,  or  a  pomade  of  iodoform,  and  cover  with  oil-silk.  In  the  later 
stages,  after  the  separation  of  the  eschars,  according  to  Hebra,  iodoform  retards  cicatri- 
zation, whilst  a  one  or  two  per  cent,  solution  of  resorcin  hastens  epithelium  formation. 

t  In  a  case  in  which  an  extensive  intra-peritoneal  dressing  of  iodoform  gauze  was 
used,  and  seven  grains  of  calomel  given  by  the  mouth,  violent  irritant  poisoning,  with 
numerous  bloody  mucous  stools  at  short  intervals,  occurred,  evidently  as  the  result  of  the 
formation  of  the  mercurous  iodide  in  the  alimentary  canal. — F.  F.  Simpson  in  a  letter. 


5i2  GENERAL    REMEDIES. 

erysipelas  and  of  anthrax  ;  also  by  P.  Baumgarten,*  who  further  found 
that  iodoform  powder  mixed  with  the  tubercle  bacillus  in  cultivating 
apparatus  did  not  prevent  its  ordinary  development,  and  that  the  bacillus 
mixed  with  iodoform  powder  when  introduced  into  guinea-pigs  and  rab- 
bits produced  rapid  tuberculosis  ;  also  by  Liibbert,7  with  the  Staphylo- 
coccus  pyogenes;  also  by  Chr.  Heyn  and  Thorkil  Drovsing,8  who  found 
that  iodoform  has  no  influence  upon  the  development  of  the  Staphylococcus 
pyogenes  or  of  the  coccus  of  pneumonia  or  of  the  Bacillus  subtilis  and 
other  organisms,  and  conclude  that  it  is  not  only  worthless  as  an  antisep- 
tic, but  may  even  be  the  means  of  carrying  the  septic  organisms  into  the 
system;  also  by  Johann  Olsen,9  with  various  bacterial  organisms;  also  by 
Konige.10  On  the  other  hand,  H.  Sattler,nin  his  experiments,  found  that 
when  he  impregnated  threads  with  iodoform  and  micro-organisms  and 
then  placed  them  in  culture-apparatus,  the  iodoform  had  a  very  distinct 
effect  in  checking  the  development  of  the  bacteria,  and  De  Ruyter  states 
that  if  instead  of  using  the  iodoform  powder  he  employed  an  ethereal 
solution  in  which  decomposition  of  the  iodoform  had  already  commenced, 
there  was  a  distinct  effect  upon  the  organisms.  In  a  further  series  of 
experiments  De  Ruyter  showed  that  iodoform  is  decomposed  by  blood, 
serum,  and  other  organic  fluids  in  which  micro-organisms  are  growing, 
and  apparently  proved  that  the  decomposition  is  produced  by  the  pto- 
maines developed  by  the  growing  organisms.  These  general  results  have 
been  abundantly  confirmed  ;f  the  antiseptic  properties  of  iodoform  de- 
pend upon  its  decomposition,  and  its  action  is  most  favorable  when  the 
processes  of  fermentation  and  of  chemical  activity  are  most  energetic.  J 

The  clinical  results  achieved  by  surgeons  are  so  concordant  and  so 
decided  that  the  practical  value  of  iodoform  in  the  treatment  of  wounds 
and  ulcers  must  be  considered  established.  It  is  possible  that  a  part  of 
the  good  influence  of  the  iodoform  is  due  to  a  specific  effect  upon  the 
tissues  of  the  wounds.  Further,  the  powder  of  iodoform  may  have  a 
very  distinct  protecting  power  both  mechanically  and  by  the  dryness  of 
the  wound  which  it  maintains,  the  discharges  from  the  wound  being  the 
especial  soil  in  which  the  bacteria  develop.  In  tubercular  diseases  iodo- 
form appears  to  exert  a  direct  influence  upon  the  bacilli.  Many  cli- 
nicians bear  strong  testimony  to  the  effect  of  iodoform  on  tubercular  ulcers 
of  the  larynx  and  other  organs.  According  to  Bruns,12  the  first  change 
which  results  from  the  use  of  iodoform  in  a  tubercular  abscess  is  the  dis- 

*  A  curious  fact  made  out  by  Baumgarteu  was  that  rubbing  the  bacillus  of  anthrax 
with  any  hard  powder  apparently  mechanically  kills  the  organism. 

t  See  especially  Neisser  (Virchow's  Archiv,  ex.),  Schnirer  (Wien.  Med.  Presse, 
1887,  ex.),  and  Kuntz  {Bcitrage  Path.  Anal.  u.  Physiolog.,  1888,  ii.).  According  to  the 
experiments  of  Altenberg  (A.  I.  P.  T.,  1901,  viii.),  the  blood,  serum,  and  urine  do  not 
liberate  free  iodine  from  iodoform,  although  the  tissues  of  various  organs,  even  when 
dried  and  powdered,  have  the  property  of  so  doing.  It  seems  to  us  probable  that  these 
tissues  depend  for  their  activity  upon  the  presence  of  micro-organisms. 

J  Moeller  has  found  that  the  iodates  and  iodic  acid  cause  symptoms  similar  to  those 
produced  by  iodine  (Inaiiff.  Diss.,  Bonn,  1877),  and  Schwerin  has  shown  that  methyi 
iodide  is  also  anaesthetic  and  hypnotic  (Centralbl.f.  Med.  Wissensch.,  1884,  146). 


ALTERATIVES.  513 

appearance  of  the  bacilli  and  appearance  of  the  normal  granular  tissues. 
The  value  of  iodoform  as  a  local  application  in  surgical  tuberculosis  seems 
to  be  firmly  established.  In  the  treatment  of  tuberculous  abscesses,  in 
tuberculous  empyema,  in  tuber cidous  joints,  in  non-suppurating  tuberculous 
glands,  and  even  in  tuberculous  peritonitis  numerous  cures  have  been 
reported.  That  the  iodoform  has  a  specific  influence  upon  the  tubercular 
organism  would  seem  to  follow  from  the  experiments  of  Gosselin,  of 
Caen,  who  found  that  guinea-pigs  saturated  with  iodoform  are  incapable 
of  contracting  tuberculosis.  The  manner  of  application  varies  with  dif- 
ferent surgeons.  Verneuil,  who  has  had  an  enormous  experience,  pre- 
fers, in  the  treatment  of  abscesses,  tuberculous  glands,  and  in  most  other 
cases,  the  injection  of  a  five  per  cent,  ethereal  solution.  Others  prefer 
glycerin  as  a  menstruum,  especially  in  empyema  ;  whilst  others,  particu- 
larly in  peritonitis,  dust  the  dry  powder  over  the  portion  which  has  been 
laid  open. 

ADMINISTRATION. — Iodoform  may  be  applied  to  ulcers  in  powder,  in 
solution,  or  in  ointment  (UNGUENTUM  IODOFORMI — ten  per  cent.,  U.  S. ). 
When  there  is  a  great  deal  of  pain,  especially  if  there  be  much  discharge, 
the  powder  is  to  be  preferred  ;  not  more  than  half  a  drachm  of  iodoform 
should  ordinarily  be  applied  to  a  wound,  although  in  cases  of  tubercidosis 
the  surgeon  is  more  than  warranted  in  taking  the  risk  of  larger  amounts. 
Verneuil  injects  at  one  sitting  never  more  than  seventy-five  grains  of  the 
iodoform.  There  is  certainly  much  truth  in  the  criticism  of  Robert," 
that  probably  in  most  cases  one-tenth  part  of  the  amount  of  iodoform 
habitually  employed  by  the  surgeon  would  suffice  for  all  therapeutic  pur- 
poses, and  that  many  lives  are  unnecessarily  endangered  by  the  excessive 
amount  of  the  drug  used.  In  uterine  cancer  and  in  painful  hemorrhoids 
cacao-butter  suppositories,  containing  from  five  to  ten  grains  of  the  drug, 
may  be  employed.  They  are  also  often  very  valuable  in  relieving 
dysenteric  and  various  irritable  neurotic  conditions  of  the  rectum.  Owing 
to  the  bad  odor  of  the  drug,  its  application  about  the  mouth  and  throat 
is  often  objected  to. 

According  to  Lewis  Elsberg,13  if  to  four  parts  of  absolute  ether  one  part  of  crys- 
tallized iodoform  be  added,  and  the  whole  shaken  in  a  red  glass  flask,  a  solution  is 
obtained  of  sufficient  strength  for  effectual  use  in  diseases  of  the  mouth,  and  free 
from  odor  other  than  that  of  ether.  Olive  oil,  saturated  with  camphor,  is  said  to 
dissolve  six  per  cent,  of  iodoform,  and  is  preferred  by  some  surgeons. 

The  quantity  required  to  take  life  is  uncertain.  Langenstein14  at- 
tributes a  death  to  four  grammes  ;  the  cause  of  the  death  seems,  however, 
doubtful.  Czerny  u  reports  death  from  six  grammes. 

TOXICOLOGY. — Whenever  any  suspicious  symptoms  arise  during  the 
use  of  iodoform,  the  dressing  should  immediately  be  removed  and  the 
part  well  washed  with  warm  water.  The  assertion  by  Sampler  and 
Retzlaff 16  that  the  potassium  bromide  is  a  chemical  antidote  by  virtue 
of  its  dissolving  iodine  compounds,  has,  so  far  as  we  know,  received  no 

33 


5i4  GENERAL  REMEDIES. 

clinical  or  experimental  confirmation,  and  there  appears  to  be  no  other 
treatment  of  iodoform-poisoning  than  the  free  internal  use  of  water,  with 
the  hope  of  aiding  in  the  elimination  of  iodine  compounds  and  the  meeting 
of  symptoms  as  they  arise. 

IODOLUM— IODOL.     U.S. 

Tetra-iodopyrrol  or  iodol,  which  is  made  by  the  action  of  iodine  upon 
pyrrol,  is  a  yellowish-brown,  shining  powder,  composed  of  long,  pris- 
matic crystals,  soluble  in  three  parts  of  absolute  alcohol,  in  ether,  and  in 
fatty  oils,  but  soluble  in  water  only  in  the  proportion  of  i  to  5000.  It  is 
tasteless  and  without  odor.  It  contains  88.9  parts  per  hundred  of  iodine, 
as  contrasted  with  96. 7  parts  contained  in  iodoform.  First  discovered  by 
Silber  and  Ciammican,  it  was  proposed  as  an  antiseptic  by  G.  Mazzoni,1 
of  Rome.  It  causes  in  the  lower  animals  (Marcus2  andT.  Pahls)  emacia- 
tion, albuminous  urine,  fall  of  temperature,  general  loss  of  muscular 
power,  and  finally  death  from  fatty  degeneration  of  the  liver,  kidneys,  and 
other  tissues.  The  assertion  that  it  is  not  capable  of  producing  consti- 
tutional symptoms  is  not  correct.  C.  Langenstein  *  reports,  as  caused  by 
the  surgical  use  of  the  drug,  dizziness,  marked  rise  in  the  temperature, 
vomiting,  small  irregular  pulse  of  136  per  minute,  albuminous  urine,  and 
apathy,  which  did  not  subside  for  four  days.  Iodine  was  found  in  the 
urine  for  two  weeks. 

In  the  experiments  of  Seifert,  iodine  was  first  detected  in  the  urine  and  saliva 
twelve  hours  after  the  ingestion  of  seven  and  a  half  grains,  did  not  reach  its  maxi- 
mum until  eighteen  hours,  and  continued  present  for  three  full  days  :  this  accords 
with  the  statement  of  Pick5  that  iodol  is  absorbed  very  slowly.  This  slow  absorp- 
tion is  probably  the  reason  that  it  is  a  less  dangerous  topical  application  than  is 
iodoform. 

Cervesato '  affirms,  with  doubtful  correctness,  that  in  man  iodol,  taken 
internally,  acts  like  preparations  of  iodine,  but  never  causes  iodism. 

THERAPEUTIC  USE. — Iodol  may  be  employed  for  all  purposes  for 
which  iodoform  has  been  used.  Mazzoni' s  solution  was  :  iodol  one  part, 
alcohol  sixteen  parts,  glycerin  thirty-four  parts.  One  drachm  of  iodol 
forms  with  one  ounce  of  ether  a  clear  brown  solution,  which  may  be  ap- 
plied by  the  spray  or  brush  to  the  nasal  and  other  mucous  membranes, 
upon  which  it  leaves  a  coating  of  iodol.  Iodol  has  also  been  used  as  an 
internal  remedy.  According  to  Assaky,  iodol  is  very  effective  in  tertiary 
syphilis  in  doses  of  from  six  to  thirty  grains  (0.4-2  Gm. )  a  day. 

THYMOLIS  IODIDUM.  U.  S.  Aristol  Annidaline,  Dithymol-Diiodide,  contain- 
ing 45  per  cent,  of  iodine,  a  light,  reddish-brown,  odorless,  crystalline  powder, 
insoluble  in  water,  very  soluble  in  fats  and  ether,  slightly  soluble  in  alcohol.  Ac- 
cording to  Neisser,1  Quinquaud  and  Fournioux,2  and  Eichhoff,  when  introduced 
even  in  very  large  amounts  into  mammals  it  produces  no  serious  intoxication. 
The  method  of  its  elimination  has  not  been  made  out.  Quinquaud  and  Fournioux 
succeeded  in  demonstrating  the  presence  of  iodine  in  the  urine  of  animals  to 
which  it  had  been  freely  given,  but  were  not  able  to  discover  traces  of  thymol. 
The  experiments  of  Neisser  seem  to  show  that  it  has  no  influence  upon  the  lower 


ALTERATIVES.  515 

organisms,  and  it  cannot  be  considered,  therefore,  as  directly  antiseptic.  It  has  been 
employed  by  a  number  of  practitioners  with  asserted  good  results  as  a  local  appli- 
cation in  inflammations  of  the  mucous  membranes  of  the  nose  and  upper  air-pas- 
sages, especially  when  there  is  absence  of  secretion  ;  also  in  psoriasis,  in  lupus,  in 
various  syphilitic  lesions,  and  as  a  substitute  for  iodoform  in  the  treatment  of  wounds. 
It  appears  to  be  free  from  irritant  properties,  and  may  be  used  in  a  strength  varying 
from  ten  per  cent,  to  the  pure  powder. 

Through  the  ingenuity  of  pharmaceutical  chemists  there  have  been  put  upon 
the  market  a  number  of  iodine  compounds,  very  few  of  which  have  real  value. 

NOSOPHEN,  the  acid  tetra-iodo-phenol-phthaiein,  is  an  impalpable,  yellow-gray, 
odorless,  tasteless,  insoluble  powder,  containing  sixty-one  and  seven-tenths  per  cent, 
of  iodine.  Its  sodium  salt,  Antinosine,  is  a  dark  blue  amorphous  powder,  readily 
soluble  in  water  and  alcohol.  Its  bismuth  salt,  Eudoxine,  is  a  reddish-yellow,  taste- 
less, odorless,  insoluble  powder.  It  is  alleged  that  nosophen  and  antinosine  are  not 
decomposed  in  the  human  body,  whilst  eudoxine  is  slowly  changed  by  the  alkaline 
juices  of  the  intestines  into  antinosine  and  bismuth.  It  is  alleged  also  that  they  are 
germicides.  As  intestinal  antiseptics,  eudoxine  being  the  best,  they  may  be  given 
in  doses  of  five  to  eight  grains  (0.3-0.5  Gm. ). 

Locally,  antinosine,  on  account  of  its  solubility,  is  preferred  as  an  application 
in  infective  inflammations  of  the  mucous  membrane,  the  strength  of  its  solution 
varying  from  one  to  three  per  cent.  According  to  Binz  and  Zantz,  when  given  intra- 
venously, antinosine  is  decomposed  and  nosophen  precipitated  in  the  blood. 

EUROPHEN,  di-isobutyl-ortho-cresol-iodide,  is  a  yellowish  amorphous  powder, 
containing  twenty-eight  and  one-tenth  per  cent,  of  iodine,  which  is  stated  to  be  de- 
composed more  slowly  than  iodoform,  and  to  be  therefore  less  poisonous.  Taken 
internally,  it  escapes  unchanged  in  great  part  or  altogether  with  the  faeces,  and  is 
said  to  be  non-toxic,  fifteen  grains  producing  no  effect  in  human  beings.  Exter- 
nally, it  has  been  employed  to  a  considerable  extent  as  a  substitute  for  iodoform,  but 
appears  to  have  some  irritant  properties. 

SOZIODOL,  di-iodoparaphenolsulphonic  acid,  contains  thirty-one  and  a  half  per 
cent,  of  mercury  and  thirty-eight  per  cent,  of  iodine  ;  it  has  been  used  as  a  local  irri- 
tant, chiefly  employed  in  the  form  of  a  powder  (talc),  fifteen  per  cent.  The  assertion 
of  A.  Liibbert,  that  it  is  as  active  as  corrosive  sublimate  as  a  germicide,  and  free 
from  poisonous  properties,  has  not  been  confirmed. 

IODOFORMOGEN,  a  compound  of  albumin  and  iodoform,  nearly  free  from  odor, 
is  a  light  yellow  powder,  insoluble  in  water,  which  has  been  used  as  a  substitute  for 
iodoform. 

OLEUM  MORRHU^E— COD-LIVER  OIL.     U.  S. 

Cod-liver  oil  is  obtained  from  the  liver  of  Gadus  morrhua  and  other 
species  of  Gadus.  In  the  manufacture  of  the  so-called  Shore  oil,  the 
only  variety  employed  in  medicine,  the  fish  caught  near  land  are  brought 
at  once  to  the  shore,  and  the  oil  is  obtained  by  forcing  steam  at  high 
pressure  through  a  mass  of  the  fresh  livers  enclosed  in  a  metallic  vessel, 
so  as  to  tear  them  into  pieces  and  melt  out  the  oil.  Cod-liver  oil  for 
medicinal  purposes  should  always  be  perfectly  limpid,  yellow,  free  from 
rancidity,  and  have  the  peculiar  taste  and  smell  of  the  oil  well  developed. 
The  cruder  varieties,  sometimes  known  as  Straits  or  Banks  oil,  used  in 
the  preparation  of  leather  and  for  other  purposes  in  the  arts,  are  prepared 
by  allowing  the  livers  to  stand  in  casks  and  undergo  putrefaction  until 


5i6  GENERAL    REMEDIES. 

the  oil  rises  to  the  top,  when  it  is  skimmed  off.  The  black  or  brown 
oil  which  results  is  extremely  disgusting  both  in  odor  and  taste,  and  is 
loaded  with  the  products  of  decomposition. 

Cod-liver  oil  is  a  very  complex  substance,  containing  glycerin,  oleic, 
margaric,  butyric,  and  acetic  acids,  gaduin,  various  biliary  principles, 
iodine,  chlorine,  traces  of  bromine,  phosphorus,  phosphoric  acid,  and  a 
peculiar  ammoniacal  base,  trimethylamine  (commercial  propylamine}, 
which  exists  in  no  other  official  oil,  but  occurs  in  ergot.  According 
to  the  U.  S.  Dispensatory,  the  proportion  of  iodine  never  exceeds  i  part 
in  2000.  Gaduin  is  a  peculiar,  dark  brown  substance,  which  is  probably 
medicinally  inert. 

PHYSIOLOGICAL  ACTION. — As  is  well  known,  all  fatty  substances 
when  taken  into  the  system  have  a  tendency  to  cause  deposition  or  for- 
mation of  fat  in  the  body.  Cod-liver  oil  certainly  shares  this  property  in 
an  eminent  degree.  Pollock  (quoted  by  Stil'l6)  has  found  that  if  there 
be  given  of  it  to  pigs  from  one  to  two  ounces  per  diem,  to  sheep  one 
ounce,  and  to  bullocks  from  three  to  nine  ounces,  it  is  digested,  and  aids 
in  fattening  the  animal  ;  larger  amounts  than  those  noted  in  Pollock's 
experiments  always  derange  very  seriously  the  digestive  function.  No 
close  studies  of  the  effect  of  cod-liver  oil  upon  healthy  men  have  been 
made.  Undoubtedly  it  tends  to  produce  obesity  ;  but,  as  no  other  oil  is 
able  to  supply  its  place  in  various  chronic  diseases,  it  must  have  some 
influence  upon  nutrition  not  shared  by  ordinary  fatty  matters,  and  there- 
fore is  an  alterative. 

The  history  of  the  clinical  use  of  oleum  morrhuse  certainly  indicates 
that  it  influences  the  constitution  of  the  blood.  It  is  an  every-day  occur- 
rence to  see  pale,  anaemic  patients  become,  while  taking  it,  rosy  and 
plethoric.  According  to  the  analysis  of  the  blood  of  a  patient  made  by 
Simon,  there  is,  during  its  use  in  phthisis,  a  great  increase  in  the  amount 
of  solids  in  the  blood,  a  diminution  of  the  fibrin,  and  an  increase  in  the 
albumin.  The  examinations  of  Dugald  Campbell *  have  confirmed  the 
results  of  Simon.  It  is  very  probable  that  cod-liver  oil  has  some  peculiar 
influence  upon  the  blood-making  organs.  Upon  the  various  single  func- 
tions of  the  body,  except  the  digestive,  cod-liver  oil  has  no  apparent  im- 
mediate effect,  disturbing  directly  neither  the  nervous,  motor,  respiratory, 
circulatory,  nor  secretory  movements.  When  by  its  use  the  general 
nutrition  is  improved,  all  the  functions  seem  to  share  equally  in  the  im- 
provement. Cod-liver  oil  has  undoubtedly,  when  given  with  sufficient 
freedom,  a  tendency  to  cause  indigestion  and  looseness  of  the  bowels.  All 
oils  are  of  difficult  digestion,  and  when  too  much  of  the  oleum  morrhuae 
is  exhibited  in  man,  as  in  animals,  it  exerts  a  deleterious  local  effect  upon 
the  alimentary  apparatus. 

Much  speculation  has  been  indulged  in  as  to  which  of  the  ingredients 
of  cod-liver  oil  impart  to  it  its  peculiar  medicinal  properties.*  Certainly, 

*  A  Gautier  and  J.  Bouillot  assert  that  they  have  found  in  cod-liver  oil  certain  alka- 
loids which  are  stimulants  to  the  circulation  and  to  the  nutrition,  and  also  to  the  kidneys, 


ALTERATIVES.  517 

however,  no  conclusion  has  been  established,  and  the  present  probabilities 
are  that  it  acts  as  a  whole, — i.e. ,  that  its  virtues  depend  upon  the  peculiar 
combination. 

The  experiments  of  Oswald  Naumann 2  indicate  that  the  physical  properties  of 
cod-liver  oil  aid  in  its  usefulness.  He  first  tested  the  rate  at  which  various  oils  pass 
through  fresh  moist  animal  membranes  when  pressed  upon  by  a  column  of  mercury 
or  by  the  weight  of  the  atmosphere  over  an  exhausted  receiver,  and  found  that  cod- 
liver  oil  passed  much  more  rapidly  than  did  any  of  a  number  of  oils  tried.  Apparently 
this  power  depended  in  some  measure  upon  the  presence  of  the  biliary  principles, 
since  if  it  was  deprived  of  them  the  rate  of  its  passage  was  greatly  lessened,  but  was 
again  increased  by  the  addition  of  a  little  bile.  The  investigator  then,  opening  the 
abdomen  of  cats,  separated  in  each  animal  by  ligatures  two  knuckles,  of  equal  length 
and  entirely  similar,  from  the  remainder  of  the  intestines.  Into  each  of  them  he  in- 
jected a  certain  amount  of  bile,  and  then  into  one  ordinary  oil,  into  the  other  cod- 
liver  oil ;  and  when  the  animals  died,  some  hours  afterwards,  it  was  always  found  that 
much  more  of  the  cod-liver  oil  was  absorbed  than  of  the  other  oil.  Naumann's  ex- 
periments were  too  few  and  incomplete  to  be  decisive,  but  they  accord  with  the  clin- 
ical observation  of  Berth6,3  who  found  that  cod-liver  oil  could  be  taken  longer 
than  other  fats  without  appearing  in  the  faeces  ;  observations  which  have  been  con- 
firmed by  Bucheim,4  as  well  as  by  J.  Gad.5  Both  Bucheim  and  Gad  believe  that  this 
absorbability  depends  largely  upon  the  presence  of  free  fatty  acids  in  the  oil,  but  it 
is  probably  due  to  the  biliary  matters,  since  H.  A.  Hare6  finds  it  greatly  increased 
by  the  addition  of  taurocholate  and  glycocholate  of  sodium.  Hare  asserts  that  cod- 
liver  oil  impregnated  with  a  small  quantity  of  the  biliary  salts  is  rapidly  absorbed 
when  rubbed  upon  the  skin,  and  proposes  the  practical  use  of  the  mixture. 

Naumann's  last  series  of  experiments  were  directed  to  discovering  the  com- 
parative ease  with  which  animal  oils  and  the  cod-liver  oil  were  oxidized.  For  this 
purpose  he  used  a  test-solution  of  potassium  permanganate,  and  on  adding  to  given 
bulks  of  this,  in  test-tubes,  equal  amounts  of  the  various  oils,  noted  the  changes  of 
color  induced  by  the  reduction  of  the  permanganate.  He  found  that  cod-liver  oil 
was  the  first  to  be  affected. 

It  is  evident  that  the  power  of  being  easily  absorbed  and  easily  oxi- 
dized fits  a  fat  for  use  in  the  animal  economy  ;  but  even  if  cod-liver  oil 
possesses  these  properties  to  a  remarkable  degree,  it  is  clear  that  they 
cannot  be  the  chief  causes  of  its  peculiar  influence  on  disease. 

THERAPEUTICS. — Cod-liver  oil  is  a  valuable  remedy  in  various  con- 
ditions of  emaciation  not  dependent  upon  diseases  of  the  alimentary  canal 
or  upon  cancerous  affections.  It  is  especially  useful  in  cases  of  the  scrofu- 
lous diathesis  and  in  tuberculous  diseases,  whether  affecting  the  soft  tissues 
or  the  bony  structure.  In  commencing  phthisis  and  even  in  the  later 
stages  it  is  of  great  value.  It  has,  however,  no  specific  relations  with  the 
tubercle  bacillus,  acting  only  by  stimulating  the  nutrition  of  the  human 
organism.  It  is,  therefore,  prominently  valuable  in  those  cases  in  which 
there  is  a  marked  tendency  to  bcdily  wasting,  and  is  of  no  service  what- 
ever in  acute  disseminated  tuberculosis.  Moreover,  it  is  as  effective  in 

and  to  which  are  largely  or  altogether  due  the  peculiar  properties  of  the  oil.  These  alka- 
loids have  been  used  in  practical  medicine  by  J.  Bouillot,8  who  affirms  that  0.15  100.25 
gramme  given  during  the  twenty-four  hours  powerfully  stimulates  nutrition,  increasing 
very  much  the  amount  of  the  urine  and  also  the  nitrogenous  elimination,  especially  of  the 
completely  oxidized  nitrogen. 


5i8  GENERAL  REMEDIES. 

various  non-tubercular  conditions  of  defective  nutrition  as  it  is  in  phthisis. 
It  is  especially  valuable  in  rickets.  It  is  often  of  service  in  advanced 
tertiary  syphilis  with  wasting  cachexia.  It  first  achieved  its  reputation  as 
a  remedy  in  chronic  rheumatism.  In  neuralgia  and  in  various  skin  dis- 
eases it  may  at  times  be  used  with  great  advantage.  It  is  not  the  disease, 
but  the  general  condition  of  the  nutrition  which  should  influence  the 
practitioner  in  the  employment  of  this  remedy. 

ADMINISTRATION. — The  chief  difficulty  in  the  use  of  cod -liver  oil  is 
the  very  common,  real  or  imagined,  inability  of  the  patient  to  take  it. 
Without  doubt,  this  very  often  arises  from  its  nauseous  taste,  to  lessen  or 
disguise  which  various  expedients  are  resorted  to. 

Sometimes  a  piece  of  salt  taken  into  the  mouth  just  before  the  oil,  which  is 
also  immediately  followed  by  another  lump  of  salt,  suffices.  It  is  said  that  some 
prefer  the  oil  in  emulsion  made  with  some  strong  aromatic  water.  The  addition  of 
an  equal  part  of  glycerin  and  one-half  to  one  drop  of  the  oil  of  bitter  almonds  to  the 
dose  certainly  lessens  the  taste  of  the  medicine.  Some  patients  take  the  oil  best  in 
the  froth  of  ale  or  porter,  the  glass  being  first  half  filled  with  the  malt  liquor,  then 
the  oil  carefully  floated  on  the  top  without  touching  the  sides  of  the  glass,  and 
the  remainder  of  the  vehicle  put  upon  the  top  of  it.  Most  of  the  patients  requiring 
oil  are  also  benefited  by  the  use  of  alcohol ;  and  our  experience  with  the  remedy 
is  that  the  most  generally  successful  plan  of  exhibition  is  to  place,  according  to 
the  exigencies  of  the  case,  from  one  to  three  tablespoonfuls  of  whiskey  or  brandy  in 
a  tumbler,  add  a  small  amount  of  water,  put  the  oil  in  the  centre,  and  toss  the  whole 
down  the  throat,  the  head  being  held  well  back,  the  mouth  wide  open,  and  the  lips 
not  touched  by  the  medicine.  The  stimulus  of  the  alcohol  often  enables  the  stomach 
to  digest  the  oil  when  otherwise  it  could  not  do  so.  Sometimes  it  is  necessary  to 
commence  with  a  single  small  daily  dose,  even  a  single  teaspoonful,  which  is  best 
taken  at  bedtime,  and  gradually  to  increase  the  amount  as  the  patient  becomes 
habituated  to  it.  Children  almost  always  learn  to  tolerate  the  taste  of  the  oil,  or 
even  become  in  a  short  time  fond  of  it. 

The  usual  dose  of  cod-liver  oil  for  an  adult  is  a  tablespoonful  three  or 
four  times  a  day  ;  for  a  child  one  year  old,  a  teaspoonful.  The  official 
Emulsum  Olei  Morrhua;  and  the  Emulsum  Olei  Morrhuce  cum  Hypophos- 
phibus,  U.  S. ,  each  contains  fifty  per  cent,  of  cod-liver  oil.  When 
infants  cannot  digest  cod-liver  oil,  inunctions  may  sometimes  be  prac- 
tised with  advantage.  N.  A.  Randolph  and  A.  E.  Roussel 7  state  that 
they  have  seen  in  such  cases  the  oil  appear  in  the  faeces. 

ACIDUM    PHOSPHORICUM— PHOSPHORIC   ACID.     U.  S. 

Phosphoric  acid,  which  results  from  the  burning  of  phosphorus  in  the 
air,  is  prepared  by  the  action  of  sulphuric  acid  upon  bone-ash,  which 
consists  chiefly  of  calcium  phosphate.  The  official  acid  contains  eighty- 
five  per  cent,  of  the  tribasic  acid  of  chemists.*  It  is  a  colorless,  inodor- 
ous, sour  liquid,  of  a  syrupy  consistence,  which  has  a  very  acid  reaction, 
and  is  corrosive  to  animal  tissues.  ACIDUM  PHOSPHORICUM  DILUTUM, 
U.  S. ,  contains  ten  per  cent,  by  weight  of  absolute  orthophosphoric  acid. 

*  It  has  been  affirmed  that  the  bibasic  pyrophosphoric  acid  is  a  cardiac  sedative  (see 
Journ.  of  Anat.  and  Physiol.,  xi.). 


ALTERATIVES.  519 

THERAPEUTICS. — Phosphoric  acid  has  been  used  considerably  as  a 
tonic  and  alterative,  especially  in  scrofulous  diseases,  but  seems  to  have 
no  other  value  than  that  of  a  very  feeble  and  doubtful  stimulant  to  the 
digestive  apparatus.  It  may  be  given  in  doses  of  five  to  fifteen  drops 
(0.3-1  C.c. ),  well  diluted. 

GLYCERO- PHOSPHORIC  ACID. — As  is  well  known,  the  nervous  tissues 
of  the  body  contain  a  notable  percentage  of  phosphorus.  It  is  present 
in  the  form  of  glycero-phosphoric  acid.  This  fact  has  led  to  its  employ- 
ment as  a  nerve  tonic  in  such  conditions  as  neurasthenia,  locomotor  ataxia, 
and  phospkaturia,  with  results  asserted  to  exceed  those  obtained  from 
phosphorus  in  any  other  form.  It  is  given  either  in  the  form  of  the 
acid  itself  or  of  sodium  or  calcium  glycero-phosphate  in  doses  of  two  to 
five  grains  (0.1-0.3  Gm. ). 

CALCIUM  PHOSPHATE. — Calcium  phosphate  is  an  abundant  ingredient 
of  bone,  but  also  exists  in  notable  quantities  in  all  the  tissues,  and  is 
probably  as  essential  to  their  health  as  to  that  of  bone.  Whenever  it  is 
taken  out  of  the  food  of  animals,  although  they  be  otherwise  well  fed, 
sooner  or  later  they  waste,  sicken,  and  die. 

Chossat *  fed  pigeons  exclusively  on  corn  containing  very  little  of  the  calcium 
phosphate,  and  found  that  after  some  months  they  wasted,  were  affected  with  diar- 
rhoea, and  died.  According  to  Roloff,2  a  herd  of  cows  which  had  been  fed  upon 
hay  from  a  certain  meadow  were  very  much  out  of  health,  and  suffered  iromfragil- 
itas  ossium.  On  examination,  the  hay  was  found  to  be  nearly  free  from  earthy 
salts,  and  upon  bone-meal  being  given  to  the  cows  they  recovered  their  health  in  four 
weeks.  The  same  authority  further  states  that  in  some  meadows  with  which  he  is 
acquainted  the  disease  is  endemic  among  the  cows  because  the  grass  is  so  poor  in 
phosphates.  Haubner 3  also  affirms  that  cattle  fed  exclusively  upon  potatoes,  or 
upon  roots  very  poor  in  phosphates,  fail  to  fatten,  become  weak,  and  are  apt  to 
suffer  from  caries,  but  that  if  the  calcium  phosphate  be  given  they  rapidly  improve  ; 
and  E.  Voit  *  states  that  rachitis  without  emaciation  can  be  produced  in  three  or  four 
weeks  in  young  dogs  by  taking  the  calcium  phosphate  out  of  the  food. 

Hegar5has  considered  the  absorption  of  the  calcium  phosphate,  when 
given  as  a  medicine,  very  doubtful,  because  when  he  exhibited  it  freely 
there  was  no  increase  in  the  amount  of  the  phosphoric  acid  or  of  the 
earthy  bases  in  the  urine.  Boker,8  on  the  other  hand,  has  found  that  if 
the  drug  be  given  to  those  wet-nurses  whose  milk  contains  an  abnormally 
small  amount  of  phosphates,  the  milk  soon  becomes  rich  in  the  earthy 
salts,  and  L.  Perl7  has  found  that  administration  of  the  phosphates  is 
followed  by  an  increase  in  their  amount  in  the  urine.  Further,  Albert 
Riesell 8  has  shown  that  the  phosphates  are  eliminated  by  the  intestines, 
and  therefore  that  even  if  it  were  a  fact  that  their  renal  excretion  is  not 
augmented  by  their  administration,  it  would  not  prove  that  they  are  not 
absorbed.  Teissier '  has  found  that  in  the  early  stages  of  phthisis  there 


520  GENERAL   REMEDIES. 

is  a  very  great  increase  in  the  excretion  of  the  earthy  phosphates  by 
the  kidney,  and  the  researches  of  Beneke  *  are  said  to  have  shown  that 
this  increased  renal  elimination,  which  plainly  occurs  in  several  allied  dis- 
eases, is  not  accompanied  by  any  increase  in  the  amount  ingested  in  the 
food  or  decrease  of  the  amount  eliminated  by  the  intestines,  and  that, 
consequently,  there  is  a  very  decided  wasting  of  the  normal  phosphates 
of  the  body.  This  being  so,  the  use  of  phosphates  in  these  diseases  is 
as  rational  as  that  of  iron  in  anaemia. 

THERAPEUTICS. — According  to  Dusart,10  to  Beneke,  and  to  Teissier, 
the  diseases  in  which  the  calcium  phosphate  is  especially  indicated  are 
rachitis,  osteomalacia,  phthisis,  and  scrofulosis.  It  is  evident  that  the 
indications  for  the  earthy  salts  are  very  strong  in  the  first  two  of  these 
affections,  and  clinical  experience  has  certainly  borne  out  the  results  of  a 
priori  reasoning.  In  scrofulosis  the  call  for  the  drug  is  not  so  plain  ; 
but  Beneke  states  that  in  many  cases,  if  the  urine  be  examined,  it  will  be 
found  to  be  abnormally  rich  in  earthy  phosphates,  and  that  under  these 
circumstances  the  remedy  is  of  the  greatest  value.  Cases  are  not  rare  of 
children  of  slow  development,  often  seemingly  well  nourished  and  robust, 
and  yet  really  pale  and  with  flabby  flesh,  but  without  any  distinct  symp- 
toms or  marks  of  scrofulosis  or  of  rachitis.  Under  these  circumstances, 
the  child  is  in  a  condition  allied  to  that  of  the  diathesis  spoken  of,  and 
calcium  phosphate  is  serviceable.  In  cases  of  delayed  union  after  fracture 
the  present  remedy  is  seemingly  indicated,  especially  since  Dusart  has 
experimentally  proved  that  when  given  to  animals  whose  bones  have  been 
broken  it  hastens  union  and  makes  the  callus  abnormally  heavy  and  firm. 
Calcium  phosphate  has  been  recommended  in  various  diseases  other  than 
those  mentioned,  but  its  value  in  them  is  much  more  doubtful.  Bennett 
commends  it  in  chronic  phthisis  ;  Piorry,"  in  syphilitic  periostitis  ;  Beneke, 
in  syphilitic  gummata  ;  Schonian,  and  also  Kugelmann,  in  the  menorrha- 
gia  of  anaemic  women.  Beneke  calls  attention  to  the  use  of  it  during  preg- 
nancy, and  believes  that  it  exerts  an  influence  on  the  fcetus,  so  that  women 
who  have  borne  only  rachitic  children  will  bring  forth  healthy  offspring. 

ADMINISTRATION. — CALCII  PHOSPHAS  PR^ECIPITATUS,  U.  S. ,  the 
Precipitated  Calcium  Phosphate,  a  white,  inodorous,  tasteless  powder, 
may  be  given  in  doses  of  ten  grains  (0.6  Gm. )  three  times  a  day.  Dis- 
solved by  means  of  lactic  acid  it  is  usually  administered  in  conjunction 
with  cod-liver  oil,  especially  as  the  so-called  emulsion  of  cod-liver  oil  and 
lactophosphate  of  lime,  which,  when  properly  prepared,  contains  fifty  per 
cent,  of  cod-liver  oil  and  two  grains  of  the  calcium  phosphate  to  the 
drachm.  Dose,  one  to  four  teaspoonfuls. 

ACIDUM  HYPOPHOSPHOROSUM,  U.  S.  {Hypophosphorous  Acid},  is  never 
used  internally  in  a  pure  condition,  but  various  combinations  of  it  with 
mineral  bases  and  alkaloids  have  been  largely  used  as  tonics  and  recon- 
structives  in  the  debility  of  phthisis,  neurasthenia,  and  allied  conditions. 

*  We  have  not  had  access  to  the  original  memoir  of  Beneke  (Zur  Wiirdigung  des 
Plwsphors  Kalkes  in  physiolog.  und  therapeut.  Bezichung,  Marburg,  1870).  See 
SchmidCs  Jahrb.,  cli.  138. 


ALTERATIVES.  521 

In  our  experience  these  combinations  have  seemed  to  exert  no  other 
influence  in  disease  than  that  of  their  active  bases.  According  to  the 
researches  of  Paquelin  and  Joly  and  of  A.  Boddaert,12  the  hypophosphites 
are  rapidly  eliminated  through  the  kidneys  in  an  unchanged  condition. 
Boddaert  affirms,  on  what  we  believe  to  be  insufficient  evidence,  that  they 
increase  distinctly  the  elimination  of  urea,  of  phosphorus,  and  of  chlorine. 
The  U.  S.  Pharmacopoeia  recognizes  CALCII  HYPOPHOSPHIS,  U.  S. 
(Calcium  Hypophosphite};  POT ASSII  HYPOPHOSPHIS,  U.  S.  (Potassium 
Hypophosphite}  ;  and  Soon  HYPOPHOSPHIS,  U.  S.  (Sodium  Hypophos- 
phite}, crystalline  salts  which  may  be  given  in  doses  of  fifteen  grains 
(i  Gm. )  each,  but  are  practically  never  used  except  in  the  form  of  the 
SYRUPUS  HYPOPHOSPHITUM,  U.  S.  (Syrup  of  the  Hypophosphites},  which 
contain  these  salts  and  may  be  given  in  doses  of  from  one  to  two  flui- 
drachms  (4-7  C.c. ),  or  of  the  SYRUPUS  HYPOPHOSPHITUM  COMPOSITUS, 
U.  S.  (Compound  Syrup  of  Hypophosphites),  which  contains,  in  addition 
to  the  other  hypophosphites  mentioned,  the  Ferric  Hypophosphite  (FERRI 
HYPOPHOSPHIS,  U.  S. ,  dose  eight  grains).  Dose  of  the  syrup,  two  flui- 
drachms  (7  C.c. ). 

COLCHICI  SEMEN— COLCHICUM  SEED.  U.  S. 
COLCHICI  CORMUS— COLCHICUM  ROOT.  U.  S. 

Colchicum  autumnale,  or  meadow  saffron,  whose  products  the  above 
drugs  are,  is  a  little  plant  growing  in  Continental  Europe  and  in  England. 
It  is  not  really  the  root  that  is  official  under  the  name  of  colchicum  root, 
but  the  thickened,  swollen  end  of  the  stem,  with  the  little  bulblet  whose 
office  it  is  to  develop  a  new  plant.  This  corm  is  solid  and  fleshy,  an  inch 
and  a  half  to  two  and  a  half  inches  in  length,  with  a  longitudinal  groove, 
having  a  nail-like  process  (the  bulblet)  at  its  base.  In  the  shops  it  is 
very  commonly  kept  in  transverse  slices,  which  are  notched  and  cordate  ; 
the  taste  is  bitter,  hot,  and  acrid.  Colchicum  seeds  are  nearly  round, 
about  an  eighth  of  an  inch  in  diameter,  and  of  a  bitter,  acrid  taste.  The 
active  principle  of  both  seed  and  corm  is  an  alkaloid,  Colchicine* 

*  The  active  principle  of  colchicum  is  without  doubt  colchicine.  See  Geiger  (Anna/. 
Chem.  Pharm.,  vii.  274),  Hoppe,  Aschoff  ( Vierteljahresschrift  f.  Prakt.  Pharm.,  vi.), 
Schroff  (Oesler.  Zeitschrift  f.  Prakt.  Heilk.,  1856),  and  Albers(Deutsche  Klinik,  1856, 
xxxvi. ).  Jacobi  affirms  that  absolutely  pure  colchicine  is  physiologically  inert,  but  that  it  is 
transformed  in  the  system  into  a  brown,  amorphous,  oxidation  product,  oxydicolchicine, 
which  produces  the  poisoning  symptoms  commonly  attributed  to  colchicine.  In  regard  to 
the  activity  of  colchicine,  Mairet  and  Combemale  (Comples-Rendus,  civ.  515)  find  that  if 
given  by  the  stomach  it  causes  when  in  the  dose  of  0.0002  gramme  per  kilogramme  in  the 
lower  animals  no  diarrhoea,  but  polyuria ;  of  0.00025  gramme  per  kilogramme,  violent  pur- 
gation, with  a  little  general  depression ;  of  0.000476  gramme  per  kilogramme,  violent  bloody 
diarrhoea,  with  salivation,  polyuria  and  great  feebleness,  lessening  of  the  temperature, 
and  rapid  respiration.  Given  hypodermically,  the  diuretic  dose  is  0.00015  gramme,  the 
purgative  dose  0.00025  gramme,  and  the  toxic  dose  0.00035  gramme  per  kilogramme. 
When  given  to  the  healthy  man  by  the  mouth  it  produces  in  doses  of  0.0002  to  0.003 
gramme  mild  headache,  muscular  weakness,  abdominal  pains,  increased  frequency  of  the 
pulse,  thirst,  and  increased  diuresis  ;  in  doses  of  0.005  gramme,  diarrhoea  and  diminution 
of  the  urine. 

Colchiceine  is  a  neutral  crystallizable  substance,  soluble  in  water,  which  is  produced 


522  GENERAL  REMEDIES. 

Local  Action.  — Absorption.  — Elimination.  — Although  preparations  of 
colchicum  brought  in  immediate  contact  with  the  mucous  membrane  do 
not  seem  to  be  immediately  and  actively  irritant,  yet  when  taken  internally 
they  produce  violent  gastro-intestinal  irritation  which  is  probably  closely 
connected  with  attempts  at  elimination.  Concerning  the  elimination  of 
the  active  principle  of  the  drug  we  have  little  knowledge,  although  it 
can  scarcely  be  gainsaid  that  the  alkaloid  escapes  with  the  urine  and, 
when  in  toxic  dose,  probably  more  largely  with  the  gastro-intestinal  secre- 
tions. 

General  Effects. — The  smallest  therapeutic  doses  of  colchicum  pro- 
duce no  distinct  symptoms.  After  somewhat  larger  amounts  there  is 
gastro-intestinal  disturbance,  as  shown  by  abdominal  uneasiness,  colicky 
pains,  borborygmi,  loss  of  appetite,  moderate  purging,  and  sometimes 
nausea, — symptoms  differing  in  degree  only  from  those  of  poisoning  by 
the  drug.  Before  these  come  on,  however,  there  is  a  lowering  of  the  pulse- 
rate,  sometimes  as  much  as  twelve  beats  per  minute,  which,  according  to 
some  authorities,  is  sometimes  accompanied  by  free  diaphoresis,  though 
it  has  never  been  our  experience  to  see  this  symptom.  Any  nervous 
symptoms,  such  as  vertigo,  headache,  or  muscular  weakness,  which  may 
be  present  as  the  result  of  the  administration  of  colchicum  are  probably 
sympathetic  from  the  gastro-intestinal  irritation. 

In  poisonous  doses  colchicum  produces  violent  purging,  whose  onset 
is  soon  followed  by  severe,  often  uncontrollable,  vomiting.  The  dis- 
charges from  the  bowels  are  at  first  large  and  serous,  but  later  become 
smaller,  more  mucous,  with  flaky  deposits,  and  finally  in  some  cases 
bloody.  Abdominal  pain  may  be  absent  or  present,  but  if  present  is 
generally  griping  ;  sometimes  there  is  gastric  burning.  Nervous  symp- 
toms have  been  prominent  in  some  of  the  severe  cases.  In  one  in- 
stance, it  is  said,  a  feeling  of  numbness  or  prickling  was  complained  of 
by  the  patient ;  but  this  seems  not  to  be  common.  Spasms  are  very 
frequent,  and  sometimes  convulsions,  which  may  be  fatal,  are  present. 
Muscular  pains  are  not  rarely  experienced  :  in  some  cases  replacing 
the  spasms,  and  probably  in  all  other  cases  coincident  with  them,  is 

by  the  action  of  mineral  acids  and  certain  other  agencies  upon  colchicine.  Its  toxic  in- 
fluence has  been  studied  upon  dogs  by  Samuel  R.  Percy  (Amer.  Med.  Times,  April,  1862, 
167),  according  to  whom  it  produced  symptoms  very  similar  to  those  caused  by  colchicine ; 
they  are — increase  in  the  frequency  of  the  pulse,  severe  purging  with  tenesmus,  vomit- 
ing, finally  great  slowing  of  the  pulse  and  failure  of  the  heart's  action,  and  death  without 
convulsions.  The  urine,  at  first  increased,  was  afterwards  suppressed.  On  post-mortem 
examination,  the  mucous  membrane  of  the  intestines  was  found  highly  inflamed,  that  of 
the  stomach  slightly  so,  and  the  heart  and  arteries  were  filled  with  black  tarry  blood, 
similar  to  that  of  colchicine-poisoning.  On  the  other  hand,  Paschkis  asserts  that  one  and 
a  half  grains  of  colchiceine  injected  into  the  jugular  vein  of  a  dog  produced  no  results 
whatever.  It  is  evident  that  the  two  experimenters  had  different  substances.  Ferrer 
(University  Med.  Mag.}  found  that  colchiceine  acts  chiefly  upon  the  motor,  and  not,  as 
does  colchicine,  upon  the  sensory  nerves,  and  that  whilst  it  stimulates  the  peripheral  vagi, 
it  does  not  depress  the  heart-muscle. 

S.  R.  Percy  affirms  that  in  gout  colchiceine  increases  the  elimination  of  urea  and  of 
uric  acid,  but  his  experiments  are  too  few  to  be  decisive. 


ALTERATIVES.  523 

great  muscular  weakness,  amounting,  as  death  approaches,  to  paralysis. 
Finally,  a  condition  of  collapse  develops,  the  circulation  fails  more  and 
more,  the  pulse,  which  has  been  frequent  and  feeble,  becomes  rapid 
and  thready,  the  skin  cold,  pale,  or  livid,  and  bedewed  with  sweat,  and 
death  from  exhaustion  results.  Consciousness  is  preserved  until  the  last. 
The  effect  of  lethal  doses  of  colchicum  on  the  urinary  secretion  varies  : 
sometimes  the  kidneys  seem  to  be  nearly  unaffected  almost  to  the  last ; 
sometimes  their  functional  activity  is  decidedly  increased,  but  in  other 
cases  it  is  diminished,  and  even  suppression  of  urine  has. been  noted. 
After  death  from  colchicum  the  blood  is  generally  found  very  dark 
and  imperfectly  coagulable,  but  whether  this  is  due  to  a  direct  action  of 
the  poison  or  is  the  result  of  the  slow  death  by  asphyxia  and  exhaustion 
has  not  been  determined.  The  chief  changes  are,  however,  in  the  ali- 
mentary canal,  the  mucous  membrane  of  which  is  much  swollen,  intensely 
congested,  sometimes  ecchymotic,  or  with  blood  free  in  the  intestine. 

Upon  most  animals  colchicum  acts  very  much  as  it  does  upon  man,  in  poison- 
ous doses  producing,  as  prominent  symptoms,  severe  and  often  bloody  purging, 
vomiting,  great  prostration,  embarrassed  respiration,  finally  more  or  less  pronounced 
paralysis,  and  death,  not  rarely  preceded  by  convulsions.  Reflex  actions  are  les- 
sened and  finally  abolished  (Albers,1  Rossbach 2)  in  the  frog  ;  but  Rossbach  affirms 
that  there  is  a  precedent  stage  of  convulsions  with  excessive  reflex  activity ;  in 
warm-blooded  animals  this  first  stage  of  excitement  is  rarely,  if  ever,  seen. 

As  colchicum  is  rarely  used  in  medicine  except  in  such  doses  as  pro- 
duce no  sensible  general  physiological  action,  being  in  fact  employed  as 
an  alterative, — i.e.,  to  affect  disease  conditions  in  some  unknown  way  by 
its  continuous  administration, — it  is  plain  that  its  physiological  action 
should  be  studied  from  two  points  of  view  :  first,  that  of  the  large 
poisonous  dose  ;  second,  that  of  the  continuous  small  dose.  In  regard 
to  the  action  of  toxic  doses  there  is  some  contradiction  on  the  part  of 
experimenters.  Rossbach  and  Adolfo  Ferrer  y  Leon s  are  in  accord  in 
affirming  that  the  drug  has  so  little  influence  upon  the  circulation  that 
any  alteration  which  occurs  in  its  poisoning  is  probably  secondary  ;  whilst 
Schaitanoff  and  Paschkis  *  state  that  the  drug  notably  increases  the  arte- 
rial pressure.  In  the  elaborate  experiments  of  Rossbach  the  motor 
nerves  and  the  striated  muscles  were  not  affected  by  the  poison,  but  the 
higher  nerve-centres,  the  spinal  cord,  and  the  peripheral  sensory  nerves 
suffered  palsy.  The  depressant  action  of  the  poison  upon  sensibility 
has  been  confirmed  by  Paschkis,  whilst  Ferrer  y  Leon  determined  that 
the  sensory  nerves  are  especially  affected,  his  results  in  this  respect  being 
concordant  with  those  of  Rossbach.  According  to  Rossbach,  the  pneu- 
mogastrics  are  not  affected  until  near  death,  whilst  the  splanchnic  nerve 
and  the  intestinal  fibres  of  the  vagi  escape  altogether.  Paschkis,  on  the 
other  hand,  states  that  the  normal  relations  of  the  intestinal  peristalsis 
with  the  pneumogastric  nerve  are  destroyed  by  colchicine. 

In  contrast  with  this  discord   is  the  universal  testimony  by  experi- 


524  GENERAL   REMEDIES. 

menters  that  the  force  of  the  poison  is  chiefly  expended  upon  the  ali- 
mentary canal,  which  is  always  found,  at  least  in  mammals,  to  be  in  a 
condition  of  intense  inflammation,  even  when  colchicine  has  been  given 
hypodermically. 

The  relief  which  is  afforded  in  a  gouty  condition  by  purgative  doses 
of  colchicum  can  readily  be  explained  by  the  supposition  that  the  drug 
causes  the  elimination  of  gout-poisons  through  the  bowels,  because  the 
effects  produced  by  doses  too  minute  to  act  upon  the  gastro-intestinal 
tract  are  ofte/i  decisive  ;  so  that  great  interest  attaches  to  the  question  as 
to  the  influence  of  the  drug  upon  the  kidneys.  It  is  certain  that  some- 
times the  continuous  moderate  use  of  colchicum  distinctly  increases  the 
flow  of  urine,  but  its  action  is  not  invariable,  and,  unfortunately,  the 
question  as  to  whether  the  drug  notably  increases  the  elimination  of  solid 
materials  from  the  urine  cannot  at  present  be  answered  with  definiteness, 
the  testimony  in  regard  to  the  action  of  colchicum  upon  the  elimination 
of  urea  and  uric  acid  in  health  and  in  disease  being  too  contradictory  and 
insufficient  to  warrant  any  conclusion. 

Thus,  Bird5  quotes  Krahmer's  experiments  as  showing  that  colchicum  does  not 
increase  the  amount  of  solids  eliminated  in  health,  and  intimates  that  his  own  inves- 
tigations had  given  similar  results  ;  whilst  Hammond,6  on  the  other  hand,  in  a  series 
of  experiments  in  which  every  care  to  avoid  fallacies,  by  maintaining  equality  as  to 
diet  and  exercise,  was  observed,  found  that  while  squill  and  digitalis  increased  only 
the  watery  part  of  the  urine,  both  the  organic  and  the  inorganic  solids  were  remark- 
ably augmented  by  colchicum. 

The  testimony  as  to  the  effects  of  the  drug  in  disease  is  no  less  discordant.  In 
1828  Chelius  announced  that  during  its  administration  in  gout  the  amount  of  uric 
acid  eliminated  is  nearly  doubled.  R.  Lewins 7  submitted  the  urine  of  several  per- 
sons suffering  from  gout,  taken  before  and  after  the  administration  of  colchicum, 
to  Christison,  who  found  in  the  colchicum-urine  the  proportion  of  urea  nearly 
double,  and  that  of  uric  acid  greater  than,  that  of  the  other  specimens. 

In  1852  Maclagan8  analyzed  the  urine  of  three  cases  of  rhematism  before  and 
after  the  exhibition  of  colchicum  :  in  two  instances  the  proportion  of  urea  was  very 
greatly  increased,  that  of  uric  acid  slightly  so.  In  the  third  case  the  effect  just  noted 
happened  at  first,  but  not  afterwards. 

On  the  other  hand,  Still6  states  that  Graves  and  Gardner  affirm  that  the  urates 
diminish  under  the  use  of  the  medicine.  It  is  evident  that  these  different  results  are 
not  so  contradictory  as  they  seem,  for  it  is  possible  that  in  one  case  the  colchicum 
may  so  act  as  to  increase  the  elimination  of  urea,  in  another  that  of  uric  acid,  and 
that  when  one  of  these  is  increased  the  other  may  be  unaffected,  or  even  diminished. 

Further,  when  the  medicine  purges  freely  it  is  very  probable  that  elimination 
by  the  kidneys  is  lessened  ;  and  no  account  of  this  is  taken  by  any  of  the  observers 
whose  original  papers  we  have  seen.  Moreover,  these  observers  also  all  contented 
themselves  with  noting  the  proportion  of  urea  and  uric  acid  in  the  urine,  when  it  is 
evident  that  the  mere  proportion,  unchecked  by  the  absolute  amount  of  urine  se- 
creted during  the  twenty-four  hours,  is  no  criterion  as  to  the  absolute  amount  elim- 
inated. A.  B.  Garrod  9  has  made  a  study  of  the  subject  in  such  a  way  as  to  avoid 
this  fallacy,  and  found  that  the  elimination  of  urea  and  uric  acid  was  sometimes  in- 
creased, but  that,  on  the  whole,  no  marked  effect  was  produced.  Noel  Patton 10 
states  that  in  his  experiments  on  dogs  small  doses  of  colchicum  increased  very  dis- 
tinctly the  elimination  of  urea  and  uric  acid,  as  well  as  the  amount  of  the  urine  ; 
while  large  doses  lessened  the  amount  of  urinary  secretion  and  increased  slightly 


ALTERATIVES.  525 

the  daily  elimination  of  urea  and  uric  acid.  He  believes  that  the  increase  was  due 
to  an  increased  production,  because  after  the  administration  of  the  drug  the  daily 
elimination  did  not  fall  below  the  normal.  We  do  not  think,  however,  that  at  present 
we  are  warranted  in  considering  it  established  that  colchicum  materially  influences 
nitrogenous  elimination. 

SUMMARY. — So  far  as  our  present  knowledge  reaches,  colchicum 
or  its  alkaloid,  when  given  in  therapeutic  doses,  produces  no  defi- 
nite symptoms  save  purgation,  and  has  no  definite  action  upon  either 
the  nervous  or  circulatory  system,  whilst  in  toxic  dose  it  paralyzes 
the  peripheral  sensory  nerves  and  finally  the  motor  tract  of  the  cord, 
together  with  the  respiratory  centre,  and  has  very  little  action  upon 
the  circulation.  Further,  it  is  most  probable  that  death  produced  by 
colchicum  is  not  due  to  any  direct  influence,  but  to  the  exhaustion 
produced  by  the  excessive  gastro-enteritis. 

As  was  first  pointed  out  by  Schroff,  and  since  confirmed  by  Rossbach,  the  ra- 
pidity of  death  in  colchicine-poisoning  is  not  at  all  in  proportion  to  the  size  of  the 
dose.  Thus,  Schroff  noticed  that  one  and  a  half  grains  of  colchicine  produced  death 
in  the  rabbit  in  fourteen  hours,  whilst  fifteen  grains  killed  in  eleven  hours.  This 
failure  of  relation  seems  to  be  explicable  only  by  the  supposition  that  colchicine 
kills  chiefly  by  its  irritant  action  on  the  alimentary  canal, [and,  not  being  in  any  dose 
corrosive,  requires  time  to  work  out  the  fatal  result,  through  the  instrumentality  of 
a  gastro-enteritis.  This  deduction  is  confirmed  by  the  long-protracted  course  of 
the  poisoning  after  small  doses.  Thus,  Aschoff  noted  death  on  the  ninth  day  in  a 
pigeon  which  had  received  one-fourth  of  a  grain  of  the  alkaloid. 

THERAPEUTICS. — Colchicum  is  of  no  value  in  practical  medicine  save 
in  the  treatment  of  gozit,  in  which  disease  it  has  long  been  recognized  as 
a  specific.  Our  acquaintance  with  its  physiological  action  is  not  suffi- 
ciently positive  to  establish  any  theory  as  to  the  method  in  which  the 
drug  acts.  It  may  be  that  it  simply  increases  the  throwing  of?  of  gout- 
poisons,  but  this  is  not  proved.  The  theory  advocated  by  Hugo  Schulz,11 
that  it  increases  very  greatly  the  circulation  in  the  capillaries  of  the  mus- 
cles and  joints,  and  thereby  brings  relief  in  gouty  states  of  passive  con- 
gestion, and  causes  absorption  of  gouty  exudates,  is  ingenious,  and  may 
or  may  not  be  true. 

Colchicum  may  be  used  to  prevent  the  coming  on  of  a  gouty  parox- 
ysm, or  to  lessen  the  severity  of  the  symptoms  when  the  paroxysm  has 
already  been  developed.  During  an  attack  of  gout,  from  ten  to  twenty 
drops  of  the  wine  of  colchicum  root  may  be  exhibited  every  four  hours 
until  some  decided  evidence  of  its  action,  such  as  nausea  or  slight 
purging,  is  induced.  It  should  always  be  borne  in  mind  that  although 
looseness  of  the  bowels  may  be  useful,  yet  severe  purging  is  to  be  avoided. 
In  some  cases,  especially  in  debilitated  subjects,  the  action  of  the  drug 
upon  the  bowels  should  be  restrained  by  the  use  of  opium  or  other  medi- 
cament. By  large  purgative  doses  of  colchicum  the  paroxysms  of  gout 
may  often  be  suppressed  ;  but  experience  has  shown  that  this  use  of  col- 
chicum is  dangerous,  the  suppression  being  sometimes  followed  by  seri- 
ous internal  disease,  apparently  due  to  a  transfer  of  the  gouty  irritation. 


526  GENERAL  REMEDIES. 

Between  the  paroxysms  colchicum  may  steadily  be  exhibited  to  the  gouty 
subject  in  small  doses  (ten  drops  of  the  wine  of  the  root  three  times  a 
day),  and  often  great  advantage  is  derived  from  its  combination  with 
potassium  iodide.  Ten  grains  of  the  iodide  and  ten  drops  of  the  colchi- 
cum wine  may  be  given  three  times  a  day. 

In  rheumatism  colchicum  has  been  highly  recommended,  but  is  of 
little  value.  Colchicum  has  been  administered  in  various  diseases,  but 
when  there  is  no  rheumatic  or  gouty  taint  is  at  present  very  rarely  used. 

TOXICOLOGY. — The  symptoms  of  poisoning  by  colchicum  have  been 
already  enumerated.  The  fatal  dose  varies,  but  is  small.  George  B. 
Wood 12  states  that  death  has  been  produced  by  two  drachms  and  a  half 
of  the  wine  of  colchicum  root,  and  Taylor13  records  a  case  in  which 
three  drachms  and  a  half  proved  fatal.  On  the  other  hand,  recovery 
has  taken  place  after  the  ingestion  of  an  ounce.*  According  to  the  ex- 
periments of  Schroff,  colchicine  is  eighty  to  one  hundred  times  stronger 
than  the  fresh  corm.  According  to  Heinrich  (quoted  by  Husemann), 
o.  1 5  grain  of  colchicine  will  produce  poisonous  symptoms  in  man,  and 
in  Krahmer'  s u  experiments  o.  3  grain  caused  in  an  adult  violent  serous 
purging,  lasting  for  four  days,  and  accompanied  by  severe  tenesmus. 
Casper  has  seen  death  result  from  a  quantity  of  the  wine  containing 
0.025  to  °-°3  gramme  (0.37-0.45  grain)  of  colchicine  ;  but,  according  to 
Husemann,  recovery  has  taken  place  after  the  ingestion  of  0.045  gramme 
of  the  alkaloid,  f  Suffet  and  Faastem  report  death  in  a  case  of  nephritis 
from  0.003  gramme  colchicine  dissolved  in  2.40  grammes  methyl  salicylate. 
The  treatment  of  colchicum-poisoning  is  as  follows.  If  the  stomach 
and  bowels  have  not  been  freely  evacuated,  administer  at  once  an 
emetic  and  a  cathartic,  so  as  to  empty  the  alimentary  canal  ;  allow  the 
patient  to  drink  freely  of  warm  water,  to  aid  in  these  operations  and  to 
act  on  the  kidneys.  Give  freely  of  tannic  acid,  as  the  only  known  chem- 
ical antidote,  although  experiments  upon  animals  have  shown  that  it  is 
not  to  be  relied  upon.  To  check  the  vomiting  and  purging,  administer 
opium  freely  ;  and  to  allay  the  irritation,  cause  the  patient  to  drink 
freely  of  albuminous  matter,  such  as  white  of  egg  dissolved  in  water  :  the 
tannic  acid  having  been  given  as  soon  as  possible  after  the  taking  of  the 
poison,  the  demulcents  are  useful  in  the  more  advanced  stages.  Symp- 
toms of  gastro-enteritis  or  of  collapse  are  to  be  met  as  they  arise. 

ADMINISTRATION. — Colchicum  is  never  used  in  substance  ;  the  wine 
of  the  root  is  deservedly  the  most  popular  preparation.  It  has  been 

*  See  case  in  Z,'  Union  Midicale,  Aug.  1848. 

t  George  W.  Major  (Canada  Med.  and  Surg.  Journ.,  Dec.  1873)  records  seventeen 
cases  of  poisoning  from  one  bottle  of  wine  of  colchicum  seeds,  occurring  in  Montreal,  seven 
of  which  proved  fatal.  The  patients  had  been  vomiting  and  purging  almost  continuously 
for  many  hours  when  first  seen,  and  the  symptoms  were  exactly  those  of  the  stage  of  col- 
lapse of  severe  cholera  morbus.  In  no  case  was  the  purging  bloody.  Consciousness  was 
preserved  to  the  last,  and  in  only  one  case  was  there  anything  like  convulsions.  There 
was  decided  numbness  of  the  extremities,  and  a  peculiar  hoarseness  of  the  voice  was 
especially  noted. 


ALTERATIVES.  527 

asserted  that  the  alkaloid  colchicine  (COLCHICINA,  U.  S. )  hypodermically 
administered  is  especially  efficacious  in  rheumatism;  the  dose  is  one- 
fiftieth  of  a  grain  (0.0013  Gm. ). 

The  official  preparations  from  the  seeds  are  :  the  tincture  (TiNCTURA 
COLCHICI  SEMINIS — ten  per  cent.),  dose,  half  a  teaspoonful  to  one  and  a 
half  teaspoonf  uls;  the  wine  (ViNUM  COLCHICI  SEMINIS — ten  percent.), 
dose,  half  a  teaspoonful  to  one  and  a  half  teaspoonf  uls ;  and  the  fluid 
extract  (FLUIDEXTRACTUM  COLCHICI  SEMINIS,  U.  S. ),  dose,  two  to  six 
minims  (0.12-0.36  C.c. ). 

The  important  preparations  of  the  root  are  :  the  wine  (ViNUM  COL- 
CHICI RADICIS,  U.  S. ,  1890 — forty  per  cent.),  dose,  ten  to  fifteen  minims 
(0.6-1.0  C.c. );  as  a  purgative  half  a  fluidrachm  (2  C.c.);  the  extract 
(EXTRACTUM  COLCHICI  CORMI,  U.  S.),  dose,  one  to  two  grains  (0.06- 
o.  10  Gm. ). 

ICHTHYOL. 

Ichthyol  is  a  substance  first  prepared  by  Schroeter  by  the  distillation 
of  a  peculiar  bituminous  sulphurous  mineral  obtained  from  the  deposits  of 
fossil  fish.  It  occurs  in  commerce  in  the  form  of  sodium  ichthyo-sul- 
phate  and  ammonium  ichthyo-sulphate.  Ammonium  ichthyol  is  a  red- 
dish-brown, clear,  thick  liquid,  of  a  hot  bituminous  taste  and  smell,  at  a 
high  heat  burning  without  ash,  making  with  water  a  clear,  reddish-brown 
solution  of  a  weak  acid  reaction,  which,  when  treated  with  hydrochloric 
acid,  yields  a  dark  resinous  precipitate.  Sodium  ichthyol  is  a  dark,  tar- 
like  substance  of  an  alkaline  reaction,  perfectly  soluble  in  water.  Both 
these  preparations  combine  with  fat  and  vaseline  in  all  proportions.  The 
ichthyol  preparations  are  said  to  contain  ten  per  cent,  of  sulphur. 

THERAPEUTICS. — According  to  Baumann  and  Schotten,  ichthyol  has 
little  apparent  action  on  the  general  system,  and  when  given  to  dogs 
in  doses  of  five  drachms  produces  no  symptoms  save  diarrhoea.  As  a 
local  remedy  it  has  been  extravagantly  praised  by  Unna,  Kiesner,  and  a 
large  number  of  German  dermatologists  and  surgeons,  and  has  also 
received  strong  encomiums  in  America.  When  applied  freely  in  a  pure 
form  to  the  sound  skin  it  produces  slight  irritation  and  burning.  It  is 
asserted  to  have,  when  used  as  a  local  application,  peculiar  alterative 
properties,  and  also  the  power  of  penetrating  through  the  skin  so  as  to 
be  able  to  act  as  an  alterative  anodyne  and  discutient  in  diseases  not 
only  of  the  skin  but  also  of  the  subjacent  tissues,  probably  having  also 
germicidal  powers.  The  cases  in  which  it  is  of  value  are  characterized 
generally  by  inflammatory  enlargement  or  inflammatory  pain. 

In  various  skin  diseases  ichthyol  has  been  used  with  alleged  remark- 
able results, — in  chronic  eczema,  chronic  urticaria,  acne,  intertrigo,  lupus, 
keloid,  etc.  In  lepra  Unna  combines  its  internal  and  external  use  (dose, 
fifteen  grains  (i  Gm.)  a  day).  It  has  also  been  recommended  in  the 
strongest  terms  for  the  relief  of  various  liberations  of  the  skin  and  for  the 
prevention  of  pitting  in  small-pox,  and  also  in  erysipelas.  In  lumbago 


528  GENERAL  REMEDIES. 

and  other  forms  of  muscular  rheumatism,  in  rheumatic  or  gouty  joint 
disease,  indeed,  in  almost  every  form  of  subacute  or  chronic  gout,  accord- 
ing to  Schweninger,  Lorenz,  and  others,  a  few  rubbings  with  pure 
ichthyol  or  a  fifty  per  cent,  ointment  will  produce  an  immediate  and  re- 
markable effect.  It  has  been  largely  used  in  the  treatment  of  sprains, 
contusions,  burns,  and  frost-bites.  If  one-half  that  has  been  said  of  it  be 
true,  it  is  a  local  remedy  of  extraordinary  power  and  value.  Schmidt  has 
even  seen  it  soften  and  disperse  a  lipoma,  and  D.  Hayes  Agnew  com- 
mends it  very  highly  in  the  treatment  of  recent  lymphatic  enlargements. 
In  sprains,  when  the  skin  is  intact  and  not  irritated,  the  ichthyol  itself  or 
a  fifty  per  cent,  ointment  may  be  employed.  In  erysipelas  Von  Nuss- 
baum  covers  the  affected  part,  after  thorough  disinfection,  with  a  thick 
layer  of  equal  parts  of  ichthyol  and  vaselin,  and  this  in  turn  with  a 
thick  layer  of  salicylated  cotton.  The  result  is  said  to  be  immediate,  the 
disease  disappearing  in  a  single  day.  In  various  skin  diseases  and  ulcer- 
ations  the  strength  of  the  application  may  vary  from  one  to  fifty  per  cent. 
Lorenz  affirms  that  in  acute  coryza  and  inflammations  of  the  nose  or 
mouth  a  mixture  of  one  to  ten  per  cent,  of  ichthyol  and  vaselin  is 
very  efficacious.  Both  Unna  and  Lorenz  deny  that  it  has  any  antiseptic 
properties. 

Ichthyol  Albuminate. — Ichthalbin  is  a  greenish-brown  powder,  made 
by  precipitating  albumin  with  ichthyol,  and  containing  seventy-five  per 
cent,  of  ichthyol.  It  is  insoluble  in  water,  but  soluble  in  alkaline  solu- 
tions ;  it  is  odorless,  almost  tasteless,  and  has  been  highly  praised  in 
syphilis  and  in  scrofidous  conditions  with  lowered  general  nutrition. 
Dose,  fifteen  to  thirty  grains  (1-2  Gm. )  three  times  a  day. 

ISAROL,  or  Ichthyodin,  made  from  crude  ichthyol  by  the  action  of  sulphuric 
acid,  is  said  to  contain  about  nine  per  cent,  of  sulphur,  to  be  soluble  in  water  and 
alcohol,  and  to  be  therapeutically  equivalent  to  ichthyol.  It  has  been  commended 
as  a  substitute  for  refined  ichthyol  on  account  of  cheapness. 

SARSAPARILLA.  U.  S. — The  roots  of  various  species  of  Smilax  inhabiting  Mexico 
and  northern  South  America  have  long  been  used  in  the  treatment  of  chronic 
syphilis  and  chronic  scrofulas.  They  contain  three  active  glucosides  belonging  to 
the  saponin  group,  namely,  parillin,  of  Palotta ;  saponin,  of  Otten  ;  sarsaponin,  of 
Schulz.  To  these  glucosides,  separate  or  combined,  various  names  have  been 
given  by  various  investigators,  such  as  smilacin,  salseparin,  sarsaparillin,  and  sar- 
illinic  acid.  Of  these  glucosides,  according  to  Robert,  sarsaponin  is  the  most 
important,  being  the  most  active  poison  to  the  red  blood-disks  known.  Palotta 
found  that  in  doses  of  thirteen  grains  parillin  causes  vomiting  and  circulatory 
depression,  but  Bocker  *  was  unable  to  obtain  such  results,  and  there  is  no  reason 
for  supposing  that  the  amount  of  these  saponins  in  sarsaparilla  is  sufficient  to  give 
to  the  drug  therapeutic  activity. 

Sarsaparilla  has  been  used  chiefly  in  the  advanced  stages  of  syphilis  as  an 
adjuvant  to  the  mercurials  and  iodides,  but  its  value  is  doubtful.  If  it  is  of  service 
it  is  in  those  cases  in  which  the  constitution  is  very  much  broken  down  by  the  disease. 
It  is  never  used  in  substance  ;  a  compound  decoction  was  formerly  much  employed, 
being  modelled  after  the  famous  Lisbon  diet-drink  ;  it  is  equivalent  to  the  present 
compound  fluid  extract  diluted.  The  Compound  syntp  of  Sarsaparilla  (SYRUPUS 


ALTERATIVES.  529 

SARSAPARILL^E  COMPOSITUS,  U.  S. )  is  an  excellent  vehicle  for  the  administration 
of  potassium  iodide,  whose  taste  it  very  well  disguises.  FLUIDEXTRACTUM  SAR- 
SAPARILL.<E,  U.  S.  {Fluid  extract  of  Sarsaparilla}.  Dose,  a  teaspoonful  three  times 
a  day.  FLUIDEXTRACTUM  SARSAPARILL^E  COMPOSITUM,  U.  S.  ( Compound  fluid 
extract  of  Sarsaparilla}  contains  sarsaparilla,  licorice  root,  sassafras,  and  meze- 
reum.  Dose,  a  teaspoonful. 

GUAIACI  RESINA.  U.  S. — Guaiac  resin  is  believed  to  be  diaphoretic  and  alter- 
ative, and  has  been  much  used  in  combination  with  sarsaparilla  in  chronic  syphilis. 
In  subacute  and  chronic  rheumatism  it  is  often  of  service.  As  suggested  by  William 
Murrell,  ten  to  thirty  grains  of  it  (0.6-2  Gm. )  may  be  given  in  electuary  as  an 
antirheumatic  laxative  in  tonsillitis,  chronic  rheumatism,  etc.  The  dose  of  the 
simple  tincture  (TINCTURA  GUAIACI — twenty  per  cent.,  U.  S.)  or  of  the  ammoniated 
tincture  (TINCTURA  GUAIACI  AMMONIATA — twenty  per  cent.,  U.  S.)  is  from  one 
to  two  teaspoonfuls  (4-7  C.c. ),  administered  preferably  in  milk,  three  or  four  times 
a  day. 

MEZEREUM.  U.  S.  Mezereon. — The  bark  of  the  Daphne  mezereum  is  said  to 
contain  a  volatile  acrid  principle  and  the  glucoside  daphnin.  In  overdoses  it  is  an 
active  poison,  producing,  it  may  be,  a  fatal  gastro-intestinal  inflammation.  In  some 
cases  the  symptoms  have  been  simply  collapse,  with  unconsciousness,  and  other 
nervous  disturbance  (case  in  British  Med.  Journ.,  1882,  ii.  521).  Internally,  meze- 
reum has  been  used  in  combination  with  sarsaparilla ;  externally  its  ointment,  for- 
merly official,  has  been  employed  as  a  stimulant  dressing  to  indolent  ulcers. 
Dose  of  the  fluid  extract  (FLUIDEXTRACTUM  MEZEREI,  U.  S.),  one  minim 
(0.06  C.c. ). 

JAMBUL. — The  bark  of  the  Eugenia  jambolana,  an  East  Indian  tree,  has  long 
been  used  in  India  as  a  stomachic  astringent  in  diarrhoea  and  as  a  specific  in  true 
diabetes.  Its  active  principle  has  not  been  determined,  but  appears  to  be  present 
in  the  bark,  in  the  seeds,  and  also  in  the  rind  of  the  fruit ;  *  neither  have  we  detailed 
knowledge  as  to  the  physiological  action  of  the  remedy. 

Thomas  Christy  *  found  that  when  sufficient  diastatic  matter  was  mixed  with 
fifty  grains  of  starch  to  convert  forty-five  per  cent,  of  the  latter  in  fifty  minutes  into 
sugar,  the  addition  of  twenty-five  grains  of  powdered  jambul  seeds  reduced  the  con- 
version of  the  starch  eighty-eight  per  cent.  In  Binz's3  experiments,  in  dogs  ren- 
dered diabetic  by  phloridzin,  according  to  the  method  of  Von  Mehring,  the 
exhibition  of  jambul  reduced  the  excretion  of  sugar  from  fifty  to  ninety  per  cent, 
without  producing  any  evidences  of  poisoning. 

In  human  glyco'suria  jambul  is  usually  without  perceptible  influence,  but  in 
some  cases  (literature  and  our  own  experience)  its  effects  are  more  marked.  It 
never  produces  any  disagreeable  effects,  and  from  fifteen  to  forty-five  minims  (0.9- 
2.7  C.c. )  may  be  given  three  times  a  day.  Vix  found  that  in  doses  of  ten  drachms 
(37  C.c.)  a  fluid  extract  made  from  the  rind  of  the  fruit  acted  efficiently  as  a  diuretic. 

THIOSINAMINE.  Allyl-sulphocarbamide ;  Allyl-sulpho-urea ;  Rhodalline. — 
This  substance,  which  is  prepared  from  the  oil  of  mustard,  occurs  in  colorless 
monoclinic  or  rhombic  crystals,  of  a  bitter  taste  and  feeble  garlic-like  odor.  It  is 
moderately  soluble  in  water,  very  soluble  in  alcohol  and  ether.  It  possesses  no 
bactericidal  properties,  and  in  the  doses  in  which  it  has  been  used  seems  to  exert  no 
influence  whatever  upon  the  general  system,  except  upon  the  blood-making  organs. 
Several  hours  after  its  injection  the  leucocytes  in  the  blood  are  greatly  diminished 
in  number,  falling,  according  to  Hebra,  in  some  cases  from  fourteen  thousand  to 
four  thousand.  This  condition  lasts,  however,  but  a  short  time,  and  is  followed  by 
a  pronounced  hyperleucocytosis.  During  the  latter  period  a  very  pronounced 
destruction  and  absorption  of  exudates  and  of  cicatricial  and  other  poorly  nourished 
tissues  are  said  to  occur. 

34 


53o  GENERAL  REMEDIES. 

Thiosinamine  was  introduced  into  medicine  by  Von  Hebra  for  the  treatment 
of  lupus  and  old  cicatrices  and  has  been  used  by  many  clinicians  in  lupus,  chronic 
glandular  inflammations,  scleroderma,  keloid,  urethral  strictures,  corneal  opacities, 
plastic  iritis  (G.  F.  Suker3),  and  sclerotic  conditions  of  the  ear  with  consequent 
deafness.  Unna  has  also  employed  it  locally  in  the  form  of  a  five  to  twenty  per 
cent,  soap  or  plaster  in  fibrous  tumors,  keloid,  leprous,  and  syphilitic  lesions,  and 
for  smallpox  scars.  Its  local  application  may  be  continued  for  some  hours,  and  is 
said  not  to  produce  irritation  or  pain.  George  E.  de  Schweinitz  informs  us  that  very 
extensive  trials  have  forced  him  to  the  conclusion  that  the  internal  administration 
of  thiosinamine  is  of  no  value  whatever  in  any  disease  of  the  eye. 

Dose,  in  capsule,  half  to  three  grains  (0.3-2  Gm. )  ;  hypodermically,  one  to 
four  grains  in  ten  to  fifteen  per  cent,  alcoholic  solution,  preferably  injected  into  the 
intracapsular  or  gluteal  region  ;  or,  when  the  disease  is  superficial,  in  the  neighbor- 
hood of  the  lesion.  Considerable  pain  is  said  to  be  produced  by  the  injection. 

TARAXACUM.  U.  S. — The  root  of  the  common  dandelion,  Taraxacum  offici- 
nale,  is  believed  to  have  the  property  of  altering  the  action  of  the  liver,  although  no 
effect  is  to  be  witnessed  from  a  single  dose  of  the  drug,  however  large, — other,  at 
least,  than  some  nausea.  Diuretic  properties  have  also  been  ascribed  to  taraxacum  ; 
but  the  only  evidence  brought  forward  to  establish  this  is  the  vulgar  name  which 
the  plant  bears  both  in  English  and  in  French.  If  taraxacum  be  useful  at  all,  it  is 
in  cases  of  dyspepsia  in  which  there  is  habitual  torpor  of  the  liver,  with  constipa- 
tion. Either  the  fluid  extract  (FLUIDEXTRACTUM  TARAXACI,  U.  S.)  or  the  solid 
(EXTRACTUM  TARAXACI,  U.  S.)  may  be  given  in  doses  of  two  to  three  drachms 
(8-i i  Gm.). 

STILLINGIA.  U.  S.  Queen' s  Root. — Stillingia  is  said  by  Bichy  to  contain  an 
alkaloid,  stillingine.  In  overdose  Stillingia  is  an  emeto-cathartic  ;  it  is  used  to  a 
considerable  extent  as  an  alterative,  especially  in  the  class  of  cases  in  which  sarsa- 
parilla  has  been  employed,  often  in  combination  with  it.  Dose  of  the  fluid  extract 
of  Stillingia  (FLUIDEXTRACTUM  STILLINGIA,  U.  S.)  is  one-half  to  one  fluidrachm 
(2-4C.c.). 

XANTHOXYLUM.  U.  S.  Prickly  Pear. — The  bark  of  two  American  spe.cies  of 
Xanthoxylum,  said  to  contain  berberine  and  other  alkaloids,  is  believed  by  various 
practitioners  to  resemble  mezereum  remedially,  and  has  been  especially  useful  in 
chronic  rheumatism.  Dose  of  the  fluid  extract  (FLUIDEXTRACTUM  XANTHOXYLI, 
U.  S. )  is  one-half  to  one  fluidrachm  (2-4  C.c. ).  Externally  xanthoxylum  is  some- 
times useful  as  a  mild  counter-irritant ;  thus,  in  chronic  pelvic  diseases,  much  tem- 
porary relief  is  often  obtained  by  a  hot  pack  applied  to  the  lower  part  of  the  trunk, 
made  with  four  ounces  of  fluid  extract  of  xanthoxylum  and  one  ounce  of  tincture  of 
cayenne  pepper  to  two  quarts  of  water. 

ANIMAL  DRUGS. 

There  have  recently  come  into  use  in  medicine  certain  substances 
derived  from  animal  tissues  which  have  the  property  of  widely  affecting 
nutrition  in  the  human  body,  and  which  probably  may  be  more  appropri- 
ately considered  under  the  head  of  Alteratives  than  in  any  other  of  the 
classes  included  in  the  scheme  of  the  present  volume. 

An  organic  remedy  whose  value  is  very  problematical  is  the  so- 
called  nuclein.  Originally  the  term  nuclein  was  applied  to  a  peculiar 
phosphorized  substance  isolated  from  the  nuclei  of  pus-cells.  Later 


ALTERATIVES.  531 

clinical  research  has  shown  that  there  are  in  nature  numerous  closely 
allied,  phosphorized,  proteid-like  bodies  to  which  the  name  may  be 
applied,  and  which  have  been  shown  by  Kossel  and  his  co-workers  to  be 
a  combination  of  nucleic  or  nucleinic  acid  with  a  proteid  body.  Nuclein 
on  a  large  scale  is  preferably  prepared  from  the  yeast-cell,  and  readily 
yields  nucleic  acid,  an  amorphous  white  powder  of  strong  acid  reaction, 
readily  soluble  in  alkalized  water,  containing  as  much  as  nine  per  cent,  of 
phosphorus,  but,  according  to  Chittenden,  no  proteid  matter.  It  occa- 
sionally exists  free  in  animal  cells  as  in  spermatozoids,  but  is  generally 
united  with  a  proteid.  Nuclein  is  furnished  to  commerce  especially  in  the 
form  of  a  five  per  cent,  solution,  of  which  the  dose  is  from  ten  to  sixty 
minims  hypodermically.  It  is  alleged  that  it  is  a  powerful  germicide,  and 
so  slightly  toxic  that  it  has  been  injected  intravenously  by  Vaughan  and 
McClintock  until  the  blood  of  the  animal  contained  one  and  one-eighth 
per  cent,  of  pure  nucleic  acid  without  serious  results.  It  has  been  espe- 
cially commended  in  the  treatment  of  tuberculosis,  puerperal  fever,  and 
other  germ  diseases. 

Among  these  animal  substances  are  certain  materials  whose  physio- 
logical and  therapeutic  value  is  doubtful,  but  whose  recent  importance  in 
medical  practice  has  been  such  as  to  forbid  them  being  passed  by  in  com- 
plete silence.  Among  these,  extracts  of  the  bone-marrow  and  of  the  spleen 
have  been  used  in  the  treatment  of  leucocythcsmia,  but  so  far  there  has 
been  no  great  success,  and  the  reason  of  the  failure  is  obvious  when  we 
remember  that  in  leucocythaemia  the  bone-marrow  and  the  spleen  are 
hypertrophied,  not  atrophied.  When  there  is  an  excess  of  white  cor- 
puscles, it  is  not  probable  that  glycerin  extracts  of  marrow  will  prove  val- 
uable, since  there  is  already  too  much  marrow  activity.  In  pernicious 
and  other  an&mias  extract  of  bone-marrow  has  been  employed  by  Frazer 
Hamilton,  J.  S.  Billings,  Jr. ,  and  others  with  varying  results.  All  that 
can  be  said  at  present  is  that  there  is  sufficient  evidence  to  warrant  the 
administration  of  the  medullary  glyceride  in  cases  of  severe  anaemia, 
although  the  probabilities  of  doing  good  are  not  great.  We  have  seen 
remarkable  results  follow  the  exhibition  of  splenic  extract  in  exophthalmic 
goitre  (see  U.  M.  M.  vii. ). 

It  is  somewhat  different  with  Brown-S€quard'  s  famous  elixir  of  testi- 
cles. As  we  know,  the  genital  glands  hold  some  relation  to  the  general  nu- 
trition. Their  removal  early  in  life  modifies  the  whole  physical  and  moral 
character  of  the  animal,  and,  therefore,  a  priori,  it  is  possible  that  there 
might  be  obtained  from  them  a  substance  which  would  have  some  effect 
upon  nutrition  ;  it  is,  however,  during  the  developmental  period  only  that 
these  glands  are  active  in  their  relation  to  nutrition,  and  clinical  results 
have  not  confirmed  the  assertions  of  Brown-S£quard  as  to  the  aphrodisiac 
and  general  stimulant  powers  of  his  elixir,  which  is  to-day  rarely  used. 
John  B.  Shober  asserts  that  the  mammary  gland  has  an  influence  on 
the  uterus,  and  affirms  that  he  has  derived  benefits  from  its  use  in  fibroid 
tumors  and  menonhagia. 


532  GENERAL   REMEDIES. 

GELATINUM— GELATIN.     U.S. 

Gelatin  is  an  albuminoid  body  derived  from  fibrous  and  cartilaginous 
tissues.  Its  use  in  medicine  depends  on  its  power  of  increasing  the 
coagulability  of  the  blood,  as  was  first  shown  by  Dastre  and  Floresco. 

Absorption  and  Elimination. — The  original  results  of  Dastre  and 
Floresco '  were  obtained  from  the  intravenous  injection  of  gelatin.  It  has 
been,  however,  since  then  abundantly  shown  that  the  drug  is  capable  of 
acting  after  hypodermic  injections,  and  it  must  be  absorbed,  therefore, 
from  the  subcutaneous  tissues.  Camus  and  Gley 2  assert  that  the  subcu- 
taneous injection  of  gelatin  can  have  no  effect  on  the  coagulability  of  the 
blood,  because,  being  an  undialyzable  substance,  it  is  incapable  of  absorp- 
tion. They  found  experimentally  that  the  introduction  of  gelatin  into 
the  peritoneal  cavity  did  not  increase  the  coagulability  of  the  blood, 
and  two  hours  after  the  injection  a  large  portion  of  the  gelatin  solution 
still  remained  in  the  peritoneal  cavity.  Lancereaux  and  Paulesco 3  deny 
the  correctness  of  the  conclusions  of  Camus  and  Gley,  claiming  that  sub- 
cutaneous injection  of  gelatin  is  equivalent  to  injecting  it  directly  into  the 
lymph  channels,  whence  it  may  be  taken  up  whether  dialyzable  or  not, 
pointing  out  as  analogous  the  fact  that  ascitic  fluid,  which  is  equally  un- 
dialyzable, is  frequently  absorbed.  They  found,  further,  that  the  intra- 
peritoneal  injection  of  gelatin  does  increase  the  coagulability  of  the 
blood,  and  that  the  solution  introduced  disappears  from  the  abdominal 
cavity. 

Concerning  the  question  of  its  absorption  from  the  intestinal  tract 
there  has  been  considerable  dispute.  It  is  impossible  that  gelatin  can  be 
absorbed  by  mucous  membranes  unchanged,  since  being  an  albuminoid  it 
is  not  dialyzable.  Many  substances,  however,  are  capable  of  producing 
changes  in  the  physical  properties  of  gelatin.  Thus  it  has  been  shown  by 
the  experiments  of  Dastre  and  Floresco  that  if  maintained  at  a  tempera- 
ture of  even  no0  C.  for  a  long  period  of  time  it  loses  the  property  of 
jellying  ;  strong  solutions  of  the  iodides  and  chlorides  also  destroy  the 
property  of  solidifying.  These  changes  are  probably  similar  to  those 
which  take  place  in  the  digestion  of  this  substance.  The  digestion  of 
albuminoids  such  as  gelatin  is  similar  to  that  of  the  true  albumins  ;  that 
is,  the  albuminoid  is  converted  by  peptic  digestion  first  into  a  substance 
allied  to  the  albumoses,  known  as  gelatose,  and  later  into  a  substance 
known  as  gelatin-peptone,  all  of  these  derivatives  being  soluble  in  water 
at  ordinary  temperatures.  According  to  the  experiments  of  H.  C. 
Wood,  Jr.,*  these  substances,  arising  from  the  digestion  of  gelatin,  like 
the  gelatin  itself,  increase  distinctly  the  coagulability  of  the  blood,  and 
being  dialyzable  are  easily  absorbed.  These  results  seem  to  indicate 
clearly  that  gelatin  given  by  the  mouth  and  being  digested  is  capable 
of  influencing  the  clotting  of  the  blood.  And  despite  the  contrary  opinions 
of  several  authors,  there  can  be  to-day  little  doubt  but  that  gelatin  acts 
when  given  by  the  stomach. 


ALTERATIVES.  533 

From  the  experiments  of  Dastre  and  Floresco  it  would  seem  probable 
that  the  gelatin  introduced  intravenously  was  eliminated  largely  un- 
changed, since  these  authors  found  that  the  urine  of  a  dog  so  treated 
solidified  on  cooling. 

It  seems  probable  that  in  its  passage  through  the  kidneys  gelatin 
acts  as  a  local  irritant.  Freudweiller 5  and  others  have  asserted  that  in 
cases  of  hematuria  it  increases  rather  than  diminishes  the  amount  of  bleeding 
from  the  kidney.  On  the  other  hand,  Schwabe,6  Hahn,7  and  many  other 
authors  have  found  that  bleeding  from  the  kidney  was  cured  by  the  drug. 

PHYSIOLOGICAL  ACTION. — That  the  coagulum  produced  by  gelatin  is 
a  true  clot,  and  not  as  was  by  some  believed,  a  jelly,  is  shown  by  the 
following  facts  :  The  process  of  clotting  takes  place  at  the  temperature  of 
38°  C. ,  at  which  temperature  gelatin  will  not  jellify,  and  gelatose, 
which  does  not  jellify  at  all,  causes  the  blood  to  clot  in  about  one-third 
the  normal  time.  Further,  it  was  found  by  Dastre  and  Floresco  that  ap- 
parently the  gelatin  does  not  enter  into  the  composition  of  the  clot,  since 
the  serum  which  is  expressed  from  the  clot  is  capable  of  solidifying  on 
cooling,  showing  that  at  least  it  contains  a  considerable  proportion  of  the 
injected  gelatin. 

There  has  been  considerable  discussion  as  to  the  cause  of  this  increase  in  the 
coagulability  of  the  blood.  Zibell8  believes  that  it  is  due  to  the  contained  lime. 
This,  however,  seems  extremely  improbable,  for  according  to  his  own  experiments 
the  proportion  of  lime  present  is  only  six-tenths  of  one  per  cent,  and  one  gramme  of 
gelatin  representing  only  0.006  gramme  of  lime  is  capable  of  distinctly  increasing 
the  rapidity  of  coagulation.  Dastre  and  Floresco  assert,  moreover,  that  gelatin  is 
not  capable  of  overcoming  the  delayed  coagulation  produced  by  decalcification  of  the 
oxalic  acid,  but  that  it  is  capable  of  overcoming  the  anti-coagulant  effect  of  peptone. 
Edsall  believes  that  the  increase  in  the  rate  of  clotting  depends  upon  the  more 
rapid  destruction  of  the  red  blood-corpuscles.  Moll 16  claims  to  have  shown  that 
gelatin  increases  the  fibrinogen  and  has  an  agglutinizing  effect  on  the  red  corpuscles. 

In  discussions  concerning  the  cause  of  the  gelatin  clot,  investigators 
have  curiously  overlooked  a  fact  known  for  a  long  time,  namely,  that 
gelatin  is  not  alone  in  its  effect  upon  the  coagulability  of  the  blood. 
Various  albuminoid  bodies  likewise  accelerate  coagulation. 

THERAPEUTICS. — Gelatin  has  been  employed  in  nearly  all  forms  of 
bleeding,  whether  internal  or  external  ;  thus,  for  example,  in  epistaxis, 
htematemesis,  and  other  local  hemorrhages  its  topical  application  is  valu- 
able. Internally  it  has  given  good  results  in  hemoptysis,  heematuria, 
purpura  hamorrhagica,  hemophilia,  and  the  like.  Kehr9  has  found  it 
useful  for  staunching  the  hemorrhage  following  operations  on  the  biliary 
system.  Lemoine 10  has  found  it  useful  to  check  the  bleeding  following 
leech-bites.  Manicotide  and  Christodulo,11  and  Bertimo-Besdetnoff,12  rec- 
ommend its  local  application  to  the  uterus  in  menorrhagia,  metrorrhagia, 
and  other  uterine  hemorrhages. 

Gelatin  has  also  been  employed  in  the  treatment  of  inoperable  aneur- 
ism, and  appears  to  be  of  value  when  the  aneurism  is  sacculated  (see 
Lancereaux  ",  M. ) 


534  GENERAL  REMEDIES. 

ADMINISTRATION. — The  intravenous  injection  of  gelatin,  we  believe, 
is  absolutely  unjustifiable,  on  account  of  the  very  imminent  danger  of  the 
formation  of  thrombi.  In  cases  where  an  immediate  action  is  not  neces- 
sary, we  believe  that  the  administration  of  gelatin  by  the  mouth  is  the 
best  method,  since  it  avoids  the  danger  of  infection,  allows  of  frequently 
repeated  doses,  and  is  probably  equally  efficient.  We  have  seen  haem- 
optysis and  long-standing  menorrhagia  controlled  immediately  by  the 
use  of  gelatin  by  the  mouth.  Rocchi la  recommends  the  administration 
of  gelatin  through  the  rectum.  The  dose  we  have  employed  by  the 
mouth  represents  from  one  to  four  drachms  of  the  dry  gelatin  three  or 
four  times  daily.  This  may  be  given  preferably  in  the  form  of  a  ten  per 
cent,  jelly,  which  may  be  flavored  to  taste.  It  must  be  remembered  in 
this  connection  that  the  ordinary  gelatin  as  prepared  for  culinary  purposes 
contains  only  three  or  four  per  cent,  of  gelatin  itself,  and  must  be  used  in 
correspondingly  large  quantities  to  have  any  effect. 

In  those  cases  of  severe  hemorrhage  where  immediate  control  of  the 
bleeding  is  necessary  and  where  local  application  is  not  practicable,  re- 
course may  be  had  to  the  hypodermic  administration.  Under  these  cir- 
cumstances the  gelatin  should  be  given  in  warm  solutions  of  from  two  to 
five  per  cent,  in  normal  saline,  of  which  from  one  hundred  to  two  hundred 
c.c.  (3-6  fluid  ounces)  may  be  given  at  a  dose.  The  technic  for  these 
injections  is  precisely  the  same  as  that  employed  for  hypodermoclysis. 
Great  care  must  be  taken  in  the  preparation  of  these  solutions,  as  in  a 
large  number  of  cases  not  only  pyogenic  infection  but  fatally  ending  tetanus 
have  been  reported  from  the  hypodermic  use  of  gelatin.  According  to 
Dorfler  even  repeated  boiling  does  not  render  the  solution  absolutely  free 
from  danger,  since  even  if  bacteria  are  killed  certain  toxins  may  not  be 
destroyed.  The  patient  may  thus  die  of  tetanus,  although  no  germs  are 
introduced.  For  hypodermic  administration  there  have  been  placed  upon 
the  market  sterilized  solutions  of  gelatin,  which  are  tested  upon  guinea- 
pigs  and  guaranteed  to  be  sterile  and  free  from  toxin.  These  solutions 
are  preferable,  but  should  be  sterilized  by  boiling  for  twenty  minutes  im- 
mediately before  using.  The  prolonged  boiling  does  not  change  the 
coagulating  effect  of  the  drug  on  the  blood.  Locally  gelatin  may  be  ap- 
plied by  means  of  a  tampon  saturated  with  a  hot  ten  per  cent,  solution. 
The  glycerinated  gelatin  (GELATINUM  GLYCERINATUM,  U.  S. )  occurs 
in  pieces  and  contains  about  fifty  per  cent,  of  gelatin. 

DUCTLESS  GLANDS. 

The  so-called  Ductless  Glands,  which  may  on  occasion  be  used  with 
advantage  as  remedial  agents,  are  the  thyroid  body,  the  suprarenal  cap- 
sules, and  perhaps  the  thymus  gland  and  the  spleen. 

THYROID  BODY. 

The  exact  function  of  the  thyroid  body  is  not  definitely  known;  the 
removal  of  it  causes  death  in  both  dog  and  man.  In  the  dog  the  lethal 


ALTERATIVES.  535 

result  takes  place  in  the  midst  of  tetanoid  symptoms,  death  occurring 
usually  during  a  convulsion.  In  man  its  absence,  congenital  or  opera- 
tive, produces  the  disease  known  as  myxcedema,  first  described  by  Ord. 
The  symptoms  of  this  disease  are  increasing  weakness  associated  with 
swelling  of  the  body,  enlargement  and  thickening  of  the  skin,  mucoid 
exudation  into  the  subcellular  tissue,  and  a  very  extraordinary  slowing 
of  all  functions.  The  appetite  is  feeble,  the  movements  are  slow,  the 
temperature  is  subnormal,  and  the  patient  thinks  with  great  slowness  ; 
as  the  days  go  on  the  universal  slowing  of  function  becomes  more  and 
more  marked  until  the  subject  sinks  into  a  condition  of  complete 
apathy  with  very  much  lowered  temperature  and  a  failure  of  all  vital 
activities. 

Baumann 1  isolated  from  the  thyroid  gland  a  proteid  substance  con- 
taining iodine,  which  he  asserted  to  be  the  active  principle  of  the  body. 
The  activities  of  this  substance,  which  is  variously  known  as  thyroiodin 
or  iodothyrin,  have  been  called  in  question  by  Gottlieb*  and  Wormser,* 
who  state  that  it  is  incapable  of  stopping  the  progress  of  symptoms 
caused  by  thyroidectomy.  But  the  contrary  results  achieved  by  E.  Roos,4 
Arthur  Hennig,  Truebel,  Ewall,  E.  Levy,5  Hildebrandt,6and  Baumann  and 
Goldmann,7  seem  to  confirm  the  claims  of  Baumann  ;  and  even  if  the  sub- 
stance be  not  the  sole  active  principle  of  the  gland,  much  therapeutic 
virtue  must  be  conceded  to  it.  Thyreoantitoxin,  which  was  described  by 
Frankel,8  contains  no  iodine,  and  appears  not  to  be  active  (Roos)  ;  a 
statement  which  is  also  true  of  the  principle  separated  by  Drechsel. 
(See  Robert  Hutchinson.9)  It  would  appear  probable  from  the  various 
researches  that  thyroiodin  is  the  chief  active  principle  of  the  thyroid 
body,  but  that  there  is  also  in  the  gland  a  second  substance  which  has 
physiological  activity. 

PHYSIOLOGICAL  ACTION. — In  elaborate  experiments  of  G.  Ballet  and 
E.  Enriquez 10  upon  dogs  it  was  found  that  half  an  hour  to  two  hours 
after  the  ingestion  of  a  full  meal  of  the  sheep's  thyroid  there  was  usually 
elevation  of  temperature,  with  great  increase  of  the  pulse-rate,  thc-ugh  in 
some  cases  the  tachycardia  alone  developed.  Rarely  there  were  general 
excitement  with  paroxysms  of  violent  tremblings  and  dyspnoea.  The 
subcutaneous  injection  of  the  extract  of  the  thyroid  caused  immediate 
fever,  tachycardia,  crises  of  trembling  and  dyspnoea,  extreme  agitation, 
and  in  two  cases  distinct  exophthalmos.  Continuous  thyroid-feeding 
produced  conjunctivitis,  general  wasting,  and  derangement  of  the  diges- 
tion, but  in  no  case  death.  On  the  other  hand,  repeated  hypodermic 
injections  of  the  extract  led  to  rapid  emaciation,  paroxysms  of  violent 
diarrhoea  and  melanaemia,  sometimes  polyuria,  sometimes  albuminuria, 
with  great  weakness  of  the  hind  legs,  occasionally  amounting  to  paralysis, 
followed  by  torpor,  collapse,  and  death.  Tumefaction  of  the  thyroid 
lobes  was  noted  in  some  cases  during  life,  and  after  death  the  thyroid 
body  was  found  to  be  greatly  enlarged  and  mottled  with  ecchymoses. 
By  microscopic  examination  there  were  revealed  marked  evidences  of 


536  GENERAL  REMEDIES. 

inflammatory  change  in  the  thyroid  gland,  with  destruction  of  the  alveolar 
and  epithelial  cells  and  the  development  of  sclerotic  tissue. 

In  man  thyroidismus ,  so  called,  has  been  developed  in  a  number  of 
cases  by  the  excessive  administration  of  the  gland.  The  chief  symptoms 
are  progressive  loss  of  weight,  shortness  of  breath,  weak,  rapid  pulse, 
and  general  nervousness. 

As  the  result  of  his  own  experiments,  Hertoghe11  asserts  that  the 
thyroid  extract  lessens  the  activity  of  the  pelvic  organs  of  women,  whilst 
it  stimulates  the  thoracic  genital  organs,  so  that  it  causes  arrest  of  men- 
struation but  increases  the  secretion  of  milk. 

According  to  Ott,  the  drug  depresses  reflex  action  in  the  frog. 

Circulation. — Vamossy  and  Vas  12  state  that  the  intravenous  injection 
of  iodothyrin  has  no  effect  on  pulse-rate,  blood-pressure,  or  respiration, 
and  attribute  the  symptoms  seen  after  its  ingestion  entirely  to  disturb- 
ances of  metabolism.  But  Haskovec,13  Oliver  and  Schafer,14  and  Ott15 
agree  that  the  thyroid  extract  causes  a  slight  fall  of  pressure,  with  some 
increase  in  pulse-rate.  According  to  Haskovec  the  fall  of  the  pressure  is 
due  to  depression  of  the  heart  muscle,  while  the  increased  pulse-rate  is 
brought  about  by  accelerator  stimulation.* 

Respiration. — Ott  found  the  respiratory  rate  increased  in  the  rabbit  by 
iodothyrin. 

Blood. — According  to  Vamossy  and  Vas,  and  Bell,16  the  thyroid  extract 
has  practically  no  effect  on  the  red  blood-corpuscles  or  haemoglobin.  M. 
L.  Perry  "  found,  as  the  result  of  thyroid-feeding  in  the  insane,  no  change 
in  the  number  of  the  white  blood-corpuscles,  but  a  marked  lessening  of 
the  percentage  of  the  multinuclear  and  a  corresponding  increase  of  the 
mononuclear  leucocytes,  results  which  agree  substantially  with  those  of 
Mosely,18  save  that  the  latter  found  some  lessening  in  the  total  number  of 
white  corpuscles.  Bell  and  Vamossy  and  Vas,  on  the  other  hand,  found 
an  increase  in  the  number  of  leucocytes  brought  about  by  the  thyroid 
body. 

Nutrition. — Although  Scholz,19  Richter,20  and  Paul  Mayer,21  failed  to 
get  evidences  of  increased  nitrogenous  elimination  over  intake,  never- 
theless, the  concordant  results  of  Roos,22  Gluzinski  and  Limberger,18 
David,24  Schondorff,25  Napier,  Mendel,  Ord,  and  others,  leave  no  room 
for  doubt  that  there  is  an  increase  in  the  destruction  of  proteid  sub- 
stances brought  about  by  the  continued  administration  of  the  thyroid. 
Roos  found  that  there  is  not  only  an  increase  in  the  excretion  of  nitrogen 
but  also  in  phosphorus  and  chlorides.  Irsai,  Vas,  and  Gara2*  have  shown 
that  these  facts  hold  true  in  goitrous,  and  Vermehren  in  myxcedematous, 
subjects. 

But  the  loss  of  weight  is  not  entirely  due  to  the  destruction  of  albu- 
minous tissues.  Thus,  in  Schondorff' s  experiments,  out  of  2.2  kilos  lost  in 
a  three  weeks'  experiment,  there  was  only  sufficient  increase  of  nitrogen 

*  The  claim  of  Cyon  (A.  G.  P.,  1898,  77,  42)  that  iodothyrin  will  restore  tone  to  an 
atropinized  vagus  has  been  disproven  by  Femgvessy  (  W.  K.  W.,  1900,  xiii.  125.) 


ALTERATIVES.  537 

excreted  to  account  for  one  kilo  of  bodily  tissues.  Bleibtreu  and  Vendel- 
stadt  attribute  only  one-sixth  of  the  weight-loss  to  the  breaking  down  of 
the  proteids.  The  conclusion  seems,  therefore,  inevitable  that  there  must 
be  under  the  influence  of  thyroid-feeding  not  only  increased  katabolism 
of  proteid,  but  also  of  fatty  tissues.  This  conclusion  is  confirmed  by 
the  results  of  Magnus- Levy,27  who  found  an  increase  in  the  absorption  of 
oxygen  and  giving  off  of  CO2  brought  about  by  thyroiodin.  In  myx- 
cedematous  subjects  the  increase  in  the  demand  for  oxygen  may  amount 
to  ninety  per  cent.  Magnus-Levy  found  Frankel's  thyreoantitoxin  to  be 
without  effect  on  the  exchange  of  gases.  Schondorff28  states  that  the 
destruction  of  nitrogenous  tissues  does  not  begin  until  the  store  of  rese'rve 
fat  is  exhausted. 

Bettmann  M  and  W.  D.  James  M  report  glycosuria  following  free  use  of 
the  thyroid  extract.  Forges 31  has  found  in  the  dog  that  the  excretion  of 
sugar  may  persist  for  weeks  after  the  withdrawal  of  the  thyroid. 

THERAPEUTICS. — It  is  evident  that  a  myxcedematous  condition  of 
the  body  is  the  result  of  the  absence  from  the  blood  of  some  principle 
or  principles  which  are  supplied  in  the  normal  animals  by  the  thyroid 
gland,  and  which  may  be  furnished  to  the  blood  by  feeding  with  thyroid 
glands.  It  is  further  apparent  that  the  myxcedematous  patient  who  has 
been  relieved  by  such  artificial  supply  must  relapse  when  the  supply  is 
cut  off  ;  so  that  treatment  of  a  myxasdema  consists  of  two  stages  ;  first, 
that  in  which  large  amounts  of  the  gland  are  administered  in  order  to 
remove  the  results  which  have  been  produced  by  the  lack  of  the  thyroid 
principle  ;  second,  the  protracted  stage  of  convalescence  in  which  small 
doses  of  the  gland  are  given  continuously  in  order  to  prevent  the  recur- 
rence of  the  myxcedemic  symptoms. 

The  destruction  of  fatty  tissues  under  its  use  would  seem  to  render  the 
drug  of  great  value  in  obesity.  Unfortunately,  however,  the  system  soon 
becomes  accustomed  to  it,  and  although  there  is  nearly  always  temporary 
benefit  in  properly  selected  cases  of  obesity  (see  page  20),  the  patients 
are  very  apt  to  relapse,  even  despite  the  continued  use  of  the  drug.* 

The  diseases  in  which  the  thyroid  body  has  been  given  include  nearly 
all  the  chronic  and  many  of  the  acute  troubles  known  to  humanity.  In  some 
of  them  it  has  seemed  to  be  of  benefit,  but  in  most  has  proved  useless. 

In  various  forms  of  skin  disease,  especially  psoriasis  (Bergmann"),  it 
has  been  recommended.  It  has  even  been  asserted  to  be  of  value  in 
lupus  (Gould33). 

In  mental  disturbances,  such  as  melancholia  or  idiocy,  not  dependent 
on  myxcedema,  it  may  be  tried,  although  the  reported  results  (Bell, 
Dobrowsky 34)  are  not  brilliant,  and  our  own  trials  have  been  an  unbroken 
series  of  failures. 

The  recorded  trials  of  it  by  Hertoghe  and  by  Mosely  in  uterine 
troubles  indicate  that  it  will  prove  of  service  in  menorrhagia,  endometritis, 

*  See  Grawitz  (Munchen.  Med.  Woch.,  1896,  43,  312),  Mathieu  (Gaz.  de  Hdp.,  Paris. 
1896,  69),  and  Yorke  Davies  (Brit.  Med.  Journ.,  1894,  ii.  42.) 


538  GENERAL  REMEDIES. 

and  kindred  disorders.  Diaballa  and  Illye"s 35  report  its  use  in  a  case  of 
nephritis  with  increase  of  the  quantity  of  urine  and  urea  and  diminution  of 
the  amount  of  albumin. 

Very  interesting  is  the  report  of  R.  Lepine 36  of  a  case  of  progressive 
myopathy,  in  which  muscles  not  very  badly  involved  so  improved  that 
the  patient,  who  had  taken  sixty  grammes  a  week  of  the  fresh  gland, 
returned  to  his  work,  refusing  to  stay  longer  in  the  hospital.  Murray 37 
has  found  it  useful  in  ununited fractures. 

In  simple  goitre, — the  goitre  of  Switzerland, — before  calcareous  de- 
generation has  taken  place,  thyroid  treatment  will  often  cause  destruction 
and"  absorption  of  the  overgrown  gland.  The  extract  has  been  used  by 
J.  William  White  with  asserted  excellent  results  in  bringing  about  the 
absorption  of  large  contracting  cicatricial  masses  which  resembled  true 
keloid.  It  has  been  employed  in  old  syphilitic  and  other  leg  ulcers,  and 
may  be  cautiously  tried  in  almost  all  forms  of  disturbed  nutrition  not 
attended  by  a  tendency  to  emaciation. 

In  any  case  the  occurrence  of  symptoms  of  thyroidism  should  be  the 
signal  for  the  lessening  or  withdrawal  of  the  dose.  In  exophthalmic  goitre 
the  extract  is  a  priori  contra-indicated,  the  most  probable  explanation  of 
the  symptoms  of  the  disease  being  an  excess  of  the  thyroid  principles  in 
the  system,  and  in  several  cases  in  which  we  have  tried  it  it  has  very  dis- 
tinctly aggravated  the  symptoms.  It  would  also  seem  to  be  contra- 
indicated  in  diabetes  mellitus. 

ADMINISTRATION. — The  thyroid  gland  may  be  given  raw  or  very 
slightly  boiled,  to  the  amount  of  a  quarter  to  half  of  the  gland  of  the 
sheep  daily.  The  glycerin  extract  or  the  dried  and  powdered  gland 
is,  however,  thoroughly  efficient  and  usually  preferable.  A  grain  of 
the  dried  gland  (GLANDULE  THYROIDE^:  SICC^E,  U.  S. )  may  in  the 
beginning  of  the  treatment  be  exhibited  three  times  a  day,  the  dose  being 
increased  until  fifteen  or  twenty  grains  (1-1.3  Gm. )  a  day  are  taken,  or 
some  nervousness,  shortness  of  breath,  rapid  pulse,  or  other  physiological 
symptoms  are  produced.  The  dose  of  iodothyrin  is  about  the  same  as 
that  of  the  dried  gland  (fifteen  grains). 


SUPRARENAL  CAPSULES. 

It  has  long  been  known  that  the  so-called  Addison's  disease,  which  is 
characterized  by  a  progressive  asthenia,  a  peculiar  bronzing  of  the  skin, 
anaemia,  and  loss  of  digestive  power,  with  excessive  vomiting,  results 
from  atrophic  or  destructive  disease  of  the  suprarenal  capsules,  but  the 
immediate  cause  of  the  symptoms  has  never  been  satisfactorily  explained. 
In  1895  Oliver  and  Schafer1  and  Szymonowicz  and  Cybulski2  published 
almost  simultaneously  papers  demonstrating  the  extraordinary  effects  of 
these  bodies  on  the  circulation. 

In  1897  Abel3  separated  a  body  in  the  form  of  benzoyl-chloride  from 
the  suprarenal  capsules,  to  which  he  gave  the  name  of  epinephrin,  and 


ALTERATIVES.  539 

which  possessed  to  a  marked  degree  the  characteristic  physiological  action 
of  the  adrenal  glands.  Subsequently  he  succeeded  in  separating  the  pure 
base.  In  1900  Von  Furth  separated  an  active  body,  to  which  he  gave  the 
name  of  suprarenin,  and  in  1901  Takamine  described  a  method  by  which 
he  isolated  a  principle,  to  which  he  gave  the  name  of  adrenalin. 

All  of  these  substances  are  extremely  active  stimulants  to  the  circulation,  as  small 
a  quantity  as  0.016  milligramme  (  ffaf  Gr.  )  of  adrenalin  per  kilo  injected  intravenously 
being  sufficient  to  markedly  elevate  the  blood-pressure.  Suprarenin  of  Von  Furth 
seems  to  be  the  same  body  as  adrenalin  of  Takamine.  Epinephrin,  on  the  other 
hand,  while  being  very  closely  allied  seems  to  be  both  chemically  and  physiologi- 
cally a  different  material.  Abel4  regards  adrenalin  as  an  epinephrin  hydrate, 
since  he  found  that  by  dehydration,  either  with  mineral  acids  or  by  heating  in 
vacuum,  adrenalin  is  converted  into  epinephrin.  He  insists  on  the  formula  for 
adrenalin  of  C10H13NO3^H2O  although  most  authorities  agree  on 


P>om  our  present  knowledge  it  seems  almost  impossible  to  say  posi- 
tively in  which  form  the  active  principle  occurs  in  nature,  since  the  com- 
plicated processes  involved  in  the  isolation  in  either  instance  might  be 
sufficient  to  cause  the  slight  difference  in  their  formula.  Practically,  how- 
ever, it  would  seem  that  both  adrenalin  and  epinephrin  represent  the 
physiological  activity  of  the  suprarenal  capsules. 

Dreyer5  found  the  active  principle  of  the  suprarenals  in  the  vein 
coming  from  the  suprarenal  capsule,  and  that  stimulation  of  the  splanch- 
nics  increased  the  amount  present  in  the  blood.  From  these  experi- 
ments it  would  seem  that  the  active  principle  of  this  vein  is  the  product 
of  a  true  glandular  secretion.  This  is  confirmed  by  the  observation  of 
Pettit,6  that  the  adrenals  are  affected  by  glandular  poisons,  as  pilocarpine, 
in  the  same  manner  as  are  the  other  glands  of  the  body. 

Langlois  7  concludes  from  his  experiments  that  there  must  be  more  than 
one  active  substance  in  the  gland  ;  a  view  which  is  also  adhered  to  by 
Corona  and  Moroni.8  It  would  seem  that  one  of  the  functions  of  the 
glands  is  to  destroy  toxic  substances. 

It  seems  established  that  the  adrenal  bodies  contain  a  considerable  amount  of 
neurin,  a  toxic  substance  resulting  from  katabolism  of  nervous  tissue,  and  that  this 
substance  appears  in  the  urine  of  persons  suffering  from  Addison's  disease  ;  and 
Albanese  has  shown  that  animals  are  less  resistant  to  neurin  after  extirpation  of 
their  adrenals.  Boinet9  (confirmed  by  J.  E.  Abelous10)  has  found  that  this  applies 
also  to  atropine  and  nicotine.  Langlois  and  Charrin  "  discovered  that  the  repeated 
injection  of  certain  toxins  in  sublethal  doses  produced  an  hypertrophy  of  the  supra- 
renal capsules  ;  but  that  instead  of  being  physiologically  more  active,  such  hyper- 
trophied  glands  lose  their  reaction  towards  ferric  chloride  and  also  their  effects  on 
the  blood-pressure.  The  fact  that  the  hypertrophied  glands  affect  the  circulation 
less  than  do  the  normal  is  very  strong  evidence  that  the  circulatory  poison  is  not 
the  same  principle  as  the  antitoxic  substance.* 

*  An  interesting  confirmation  of  the  fact  is  the  observation  of  Caussade"  that  the 
glycerin  extract  of  the  suprarenals  when  injected  continuously  produces  an  hypertrophy 
of  the  suprarenals  precisely  as  do  other  toxic  bodies  ;  suggesting  that  the  gland  destroys 
its  own  secretion  when  in  excessive  amount. 


540  GENERAL  REMEDIES. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Locally  applied  the  ex- 
tract of  the  suprarenals  acts  as  a  powerful  constrictor  of  the  blood-vessels. 
It  has  of  itself  no  local  anaesthetic  properties,  but  when  used  in  con- 
junction with  cocaine,  enhances  the  powers  of  that  drug,  probably  by  its 
action  on  the  blood-vessels. 

Elimination. — The  active  principle  of  adrenals  is  very  rapidly  de- 
stroyed or  eliminated  in  the  system,  since  the  effects  do  not  last  much 
over  ten  or  fifteen  minutes.  Cybulski  discovered  that  the  urine  of  ani- 
mals poisoned  with  suprarenals  is  capable  of  producing  a  rise  in  the 
blood-pressure,  and  therefore  believed  that  the  active  principle  is  elimi- 
nated by  the  kidneys.  Ott  and  Harris 13  confirm  this  fact,  but  assert  that 
it  can  be  shown  only  after  enormous  doses  have  been  given.  It  would 
seem,  therefore,  that  only  a  part  of  the  drug  is  eliminated  by  the  kidneys. 
Langlois  u  found  that  maceration  with  the  liver  destroyed  the  active  prin- 
ciple of  the  gland,  that  ligation  of  the  hepatic  vein  prolonged  the  duration 
of  its  effect,  and  that  when  injected  into  the  portal  vein  the  suprarenal 
had  comparatively  small  influence  upon  the  circulation.  This  last  fact  has 
been  also  noted  by  Carnot  and  Joserand,15  who  further  determined  that 
injection  into  the  femoral  artery  likewise  destroys  the  activity  of  adrenalin. 
It  would  seem,  therefore,  that  it  is  largely  oxidized  in  the  liver  and  mus- 
cular tissue.  Erhmann33  believes,  however,  that  adrenalin  is  neither 
eliminated  nor  destroyed,  because  he  finds  remaining  in  the  blood  after 
the  pressure  has  fallen  to  the  normal  more  than  sufficient  of  the  principle 
to  act  as  a  circulatory  stimulant,  and  because  the  blood  of  such  an  animal 
is  capable  of  causing  a  rise  of  pressure  in  another  animal. 

General  Effect. — The  most  manifest  action  of  suprarenal  bodies  is 
upon  the  circulation,  so  that  after  the  exhibition  of  anything  like  the 
therapeutic  dose  the  only  symptoms  produced  are  connected  with  the 
circulation. 

Toxic  doses  of  the  extract  caused  in  the  frog  progressively  increasing 
loss  of  power  without  a  true  paralysis,  which  seems  to  be  of  spinal  origin, 
since  Gourfein  and  Oliver  and  Schafer  find  that  after  ordinary  toxic  doses 
the  nerve-trunks  and  muscles  preserve  their  activity  up  to  death  ;  on  the 
other  hand,  Vincent 16  asserts  that  the  suprarenal  extract  is  a  muscle- 
poison,  producing,  when  given  to  the  frog  in  overwhelming  doses,  a  pecu- 
liar rigidity  similar  to  that  brought  about  by  veratrine. 

According  to  Abel17  and  Abbott,18  epinephrin  kills  by  arrest  of  the 
respiration.  This  paralytic  effect  upon  the  respiratory  centres  is  preceded, 
if  the  dose  has  not  been  too  large,  by  an  enormous  increase  in  the  rate  of 
the  breathing.  The  lethal  dose  for  a  rabbit,  according  to  Abel,  is  about 
ten  milligrammes. 

The  injection  of  the  suprarenal  extract  or  its  active  principle  has  been  shown 
by  a  number  of  observers  to  produce  glycosuria.  Croftan 19  found  in  the  suprarenal 
extract  a  diastatic  ferment  which  was  capable  of  producing  glucose  from  glycogen, 
but  Hurter  and  Richards20  have  shown  that  Takamine's  adrenalin  does  not  affect 
solutions  of  glycogen,  although  it  causes  the  occurrence  of  sugar  in  the  urine. 


ALTERATIVES.  541 

They  attribute  this  effect  to  an  action  on  the  pancreas,  since  they  found  degenera- 
tion of  the  islands  of  Langerhans  after  adrenalin-poisoning. 

Patton"  determined  that  adrenalin  was  capable  of  causing  the  formation  of 
sugar  from  the  proteids  after  the  destruction  of  the  carbohydrates  of  the  body; 
the  glycosuria  he  therefore  regarded  as  a  true  diabetes. 

Nutrition. — Although  the  effect  of  suprarenal  feeding  on  nutrition  seems 
to  be  of  minor  importance,  it  has  been  abundantly  proven  that  either  the 
dried  capsules  or  adrenalin  is  capable  of  producing  glycosuria.  This  is 
accompanied  with  an  increased  amount  of  sugar  in  the  blood  and  appar- 
ently disappearance  of  glycogen  from  the  liver  (see  Paton36). 

Drummond37  has  shown  that  adrenalin  is  capable  of  giving  rise  to 
acute  parenchymatous  nephritis. 

Circulation. — After  the  intravenous  injection  of  the  suprarenal  extract 
or  its  active  principle,  there  occurs  a  maxked  rise  of  the  blood-pressure 
accompanied  by  a  slowing  of  the  pulse.  When  the  blood-pressure  has 
reached  its  maximum,  the  pulse  becomes  rapid. 

According  to  Cyon,"  this  increase  in  the  rate  of  the  pulse  is  brought  about  by 
a  heightened  excitability  of  the  accelerator  centre.  Amberg  has  shown  that  the 
slowing  of  the  pulse  is  not  dependent  upon  a  rise  of  the  blood-pressure  as  is 
claimed  by  Gearheart,23  but  is  due  to  a  stimulation  of  the  inhibitory  centre,  being 
abolished  either  by  section  of  the  vagi  or  the  injection  of  atropine.  The  rise  of  the 
pressure  is  not  prevented  by  division  of  the  splanchnics  (Cyon)  nor  of  the  spinal 
cord  (Oliver  and  Schafer).  Meltzer  and  Meltzer24  and  Josue25  have  shown  that  the 
division  of  the  sympathetic  does  not  prevent  the  constriction  of  the  vessels  in  the 
ear  of  the  rabbit  on  the  corresponding  side.  In  fact,  according  to  the  former  in- 
vestigators, the  contraction  was  more  marked  on  the  side  whose  nervous  influences 
had  been  destroyed  than  on  the  other  side.  Gottlieb w  has  determined  that  the 
vessels  of  an  isolated  kidney  which  had  previously  been  dilated  with  chloral 
hydrate  were  contracted  by  the  suprarenal  extract.  The  pulmonary-pressure, 
according  to  both  Velich  and  Gearheart,  is  slightly  elevated  by  the  adrenals. 

Ott  and  Harris 1S  have  found  that  adrenalin  applied  externally  to  the  isolated 
frog  heart  produce  a  temporary  decrease  of  both  force  and  rate  followed  by  an 
increase  in  the  same,  and  Gottlieb  has  found  that  the  isolated  mammalian  heart  is 
also  stimulated  by  the  suprarenal  extract.  With  very  large  doses  the  rise  of  pres- 
sure is  followed  by  a  gradual  fall  to  the  zero  point,  the  heart  ceasing  in  diastole. 

From  the  results  of  these  observers  it  would  seem  that  epinephrin 
stimulates  the  muscular  walls  of  the  heart  and  of  the  blood-vessels  or  else, 
as  Gottlieb  believes,  their  contained  motor  ganglia  and  the  cardiac  inhibi- 
tory centres. 

A  remarkable  effect,  first  demonstrated,  we  believe,  by  Josu6, — and 
confirmed  by  Kulbs34,  Erb35  and  others, — is  atheroma  and  even  calcifica- 
tion of  the  arteries  following  the  repeated  injections  of  adrenalin.  Kulbs 
has  demonstrated  in  the  rabbit  not  only  hardening  of  the  walls,  but  aortic 
aneurism  which,  in  one  case  ruptured  with  fatal  hemorrhage.  This  oc- 
curred after  thirty-one  injections  given  twice  a  day.  According  to 
Erb  these  changes  are  dependant  upon  a  direct  toxic  influence  on  the 
muscle-fibers  of  the  vessel  walls.  Besides  the  lesions  in  the  arterial  walls, 


542  GENERAL  REMEDIES. 

pulmonary  oedema  has  been  reported  by  Kulbs  and  others  as  a  secondary 
result  of  the  use  of  adrenalin. 

THERAPEUTICS. — There  is  at  present  considerable  clinical  as  well  as 
experimental  evidence  to  show  that  the  extract  of  the  suprarenal  capsule 
is  of  value  in  the  treatment  of  Addison'  s  disease.  It  is  plain,  however, 
that  when  the  lesion  of  the  adrenals  is  cancerous  or  tubercular,  supplying 
artificially  to  the  system  an  active  principle  prepared  by  those  bodies 
cannot  affect  the  progress  of  the  local  disease  and  therefore  cannot  bring 
about  a  cure. 

The  most  important  therapeutic  use  of  this  drug  depends  upon  its 
influence  upon  the  blood-vessel  walls  when  locally  applied.  It  is  used  to 
counteract  the  vascular  engorgement  in  the  treatment  of  various  inflam- 
mations of  the  mucous  membranes,  as  rhinitis,  pharyngitis,  conjunctivitis 
and  the  like. 

According  to  Konigstein ""  and  De  Schweinitz,  the  retinal  vessels  are 
not  affected  when  the  drug  is  instilled  into  the  eye.  It  does  not  dilate 
the  pupil  *  nor  influence  accommodation.  It  seems  to  possess  the  power 
of  penetrating  the  skin  and  of  whitening  the  hyperaemic  skin  of  chronic 
eczema, 

It  is  difficult  to  say  precisely  what  value  this  method  of  treatment 
has  in  acute  inflammation.  De  Schweinitz28  is  of  the  opinion  that, 
although  the  application  of  the  suprarenal  solutions  will  produce  a 
blanching  of  the  inflamed  part,  it  does  not  hasten  the  cure  of  the  dis- 
ease, and  Kyle  has  seen  cases  of  acute  coryza  made  decidedly  worse 
by  the  treatment.  In  liay  fever  it  frequently  gives  good  results,  but  in 
many  cases  fails  entirely  to  relieve  the  symptoms.  On  account  of  its 
local  vaso-constrictor  action  it  is  also  of  use  in  controlling  local  hemor- 
rhages, as  epistaxis,  hczmatemesis,  enteric  hemorrhages  in  typhoid  fever. 
Various  authors  recommend  it  for  the  purpose  of  preventing  hemorrhage 
during  operations  on  the  throat  and  eye.  As  pointed  out  by  Kyle,29 
operations  done  under  adrenalin  ischaemia  are  likely  to  be  followed  by 
post-operative  bleeding.  Its  effect  in  constricting  the  blood-vessels  is  not 
likely  to  make  it  of  any  value  as  a  styptic  in  internal  hemorrhages. 
Carnot  and  Joserand M  have  shown  that  if  injected  intravenously  it  does 
not  produce  visceral  haemostasis.  Moreover,  these  authors  find  that  its 
action  as  a  local  styptic  differs  very  markedly  in  different  portions  of  the 
body.  Thus,  when  injected  in  the  kidneys  it  has  no  haemostatic  action  at 
all  ;  much  less  power  when  applied  to  the  intestines  or  stomach,  than  in 
the  nose. 

Suprarenal  extract,  and  its  active  principle,  have  been  suggested 
and  to  a  certain  extent  used,  as  circulatory  stimulants  in  conditions  of 
sudden  circulatory  failure,  especially  in  shock  during  operation.  The  ex- 
treme fugaciousness  of  its  action  makes  it,  however,  even  in  these  acute 

*  Meltzer,  Ott,  and  Harris  assert  that  after  section  of  the  cervical  sympathetic  it  does 
dilate  the  pupil. 


ALTERATIVES.  543 

conditions,  of  comparatively  little  value,  and  the  effects  of  its  repeated 
use  in  causing  arterial  and  pulmonary  oedema,  render  its  repeated  use  very 
dangerous.  We  have  seen  patients  whom,  we  believe,  were  being  killed 
by  confidence  in  this  drug  as  a  circulatory  stimulant.  Internally  it 
has  been  recommended  by  Cohen  for  the  relief  of  asthma  and  hay  fever, 
and  by  Floersheim Sl  in  endocarditis,  but  it  is  extremely  doubtful  if  it  is  of 
value  in  either  of  these  conditions.  Schafer32  recommends  its  employ- 
ment in  uterine  hemorrhages,  as  does  also  Floersheim.  The  former 
believes  that  it  controls  the  hemorrhage  by  stimulation  of  the  uterine 
muscle. 

ADMINISTRATION. — Locally  the  suprarenal  gland  may  be  used  in  the 
form  of  a  watery  extract  of  from  five  to  twenty  per  cent.  Adrenalin  may 
be  applied  in  strengths  varying  from  i  to  100  to  i  to  10,000,  either  by 
atomizer  or  by  tampon.  Internally  the  dried  suprarenals  (GLANDULE 
SUPRARENALES  Sicc.<E,  U.  S. )  may  be  given  in  doses  of  from  three  to 
five  grains  (0.2-0.3  Gm.).  Of  the  i  to  1000  solution  of  adrenalin  from 
five  to  thirty  minims  (0.6-2.0  C.c. )  may  be  given  hypodermically.  In 
Addison's  disease  the  crude  gland  is  preferable  to  any  of  the  active 
principles. 

PITUITARY  BODY. — We  have  very  little  knowledge  of  the  physiologi- 
cal value  of  the  hypophysis  and  almost  none  of  its  therapeutic  value. 
Its  extract  causes  a  marked  rise  of  pressure,  which  Oliver  and  Schafer l 
attribute  to  a  contraction  of  the  arterioles,  and  slowing  of  the  pulse,  which, 
according  to  Cyon,2  is  not  prevented  either  by  section  of  the  vagi  or  by 
atropine.  Several  investigators  have  failed  to  find  any  pharmacological 
activity  in  the  hypophysis  cerebri.  The  explanation  of  this  discrepancy 
is  offered  by  the  discovery  of  Howell,3  that  the  pituitary  gland  proper  is 
destitute  of  active  properties,  the  stimulant  principle  residing  slowly  in 
the  infundibular  body  sometimes  known  as  the  posterior  lobe  of  the 
hypophysis.  Schiff4  has  found  that  the  pituitary  body  causes  an  in- 
creased elimination  of  phosphates  without  corresponding  increase  of  the 
nitrogenous  elements. 

We  know  of  no  condition  in  which  the  pituitary  body  is  of  therapeutic 
use.  Mairet  and  Bosc 5  have  tried  it  in  epilepsy,  but  with  no  benefit 

SPLEEN. — In  a  case  of  severe  chronic  exophthalmic  goitre  which  was 
under  H.  C.  Wood's  care  some  years  ago  an  acute  splenitis  ending  in 
abscess  developed.  In  the  second  or  third  week  of  the  attack  the  en- 
larged thyroid  body  began  to  diminish,  and  by  the  fifth  week  had  disap- 
peared. After  a  protracted  and  extremely  severe  illness  the  woman 
finally  recovered  from  the  splenic  abscess,  and  has  since  remained  free 
from  any  symptoms  of  exophthalmic  goitre. 

In  myxcedema,  cretinism,  etc. ,  it  is  well  known  that  the  spleen  is  fre- 
quently enlarged,  suggesting  that  there  is  some  relation  between  this 
organ  and  the  thyroid  body.  That  the  splenic  extract  is  not  inert  is  shown 


544  GENERAL  REMEDIES. 

by  the  discovery  of  Oliver  and  Schafer,  that  its  intravenous  injection  in  the 
dog  produced  a  fall,  followed  by  a  marked  rise,  in  the  arterial  pressure. 

We  have  used  the  splenic  extract  in  various  cases  of  exophthalmic 
goitre,  and  have  found  that  two  practical  difficulties  attend  its  adminis- 
tration. If  it  be  given  by  the  mouth  in  sufficiently  large  doses  to  produce 
distinct  effect  it  is  very  apt  to  cause  nausea  and  sick  stomach.  If  it  be 
given  hypodermically  it  frequently  causes  local  abscesses.  The  few  trials 
we  have  made  of  it  indicate  that  it  is  at  least  worthy  of  being  essayed  in 
this  intractable  disorder.  Clark '  has  found  the  extract  of  spleen  useful 
in  cases  of  insanity  dependent  on  physical  exhaustion,  as  in  puerperal 
•weakness  or  an&mia. 

TOXINS   AND    ANTITOXINS. 

The  second  class  of  animal  substances  to  which  value  as  remedial 
agents  must  be  allowed,  consists  of  those  which  are  the  products  of  bac- 
terial growth  in  the  animal  organism.  The  history  of  the  develop- 
ment of  these  substances,  .of  their  physiological  activity,  and  of  their 
value  in  the  treatment  of  disease  is  of  such  extent  that  in  a  treatise  like 
the  present  the  subject  cannot  be  thoroughly  discussed  ;  only  a  very 
brief  mention  of  the  more  important  remedies — of  their  value  and  method 
of  use — can  be  made.  For  details  the  reader  is  referred  to  special  trea- 
tises on  bacteriology. 

It  is  now  known  that  many  and  probably  all  pathogenic  germs  pro- 
duce in  the  animal  organism  two  classes  of  substances  capable  of  violently 
affecting  nutrition,  which  substances  are  believed  by  chemists  to  be  of 
albuminous  nature. 

To  one  class  has  been  given  the  name  toxin,  to  the  other  that  of  anti- 
toxin. The  toxin  is  the  substance  produced  by  the  bacteria  beneficial  to 
the  bacteria  themselves,  whilst  the  antitoxin,  although  produced  by  the 
bacteria,  is  hostile  to  them.  In  infectious  diseases  there  is  a  battle  be- 
tween the  toxins  and  the  human  animal  aided  by  the  antitoxins.  The 
toxin  has  a  twofold  action.  It  acts  locally  as  a  poison  and  also  affects 
the  general  system.  Thus,  the  bacillus  of  diphtheria,  growing  upon  the 
throat,  forms  there  a  toxin  which  attacks  the  immediately  surrounding 
tissue,  and  so  weakens  it  that  the  germ  is  capable  of  overcoming  the 
natural  resistance  of  the  part.  By  and  by,  as  the  toxin  is  absorbed  into 
the  blood,  it  affects  the  general  system  and  produces  the  constitutional 
symptoms  and  some  of  the  wide-spread  lesions  of  diphtheria.  That  the 
role  of  the  toxins  is  important  is  shown  by  the  fact  that  various  pathogenic 
bacteria  introduced  into  the  living  animal  without  any  accompanying 
toxin  are  unable  to  overcome  the  resistance  of  the  tissues  and  fail  to 
develop. 

The  mode  of  action  of  the  antitoxin  in  infectious  diseases  has  been  the 
subject  of  a  large  amount  of  surmise  and  study,  but  while  a  number  of 
interesting  theories  have  been  suggested,  notably  that  of  Ehrlich,  it  must 
be  confessed  that  we  have  no  positive  knowledge  of  the  manner  in  which 


ALTERATIVES.  545 

this  substance  acts  in  infectious  diseases.  It  seems  probable  that  the 
actions  of  different  serums  are  not  the  same.  If  antitoxin  be  given  to 
an  animal  suffering  from  an  infectious  disease  due  to  local  lodgement  of  a 
pathogenic  germ,  the  first  evidence  of  its  beneficial  action  is  the  failure  of 
the  germs  to  grow,  though  they  are  not  killed. 

The  toxin  of  tubercle  bacillus,  prepared  in  various  manners,  was  orig^ 
inally  recommended  in  the  treatment  oi  phthisis  \yy  Koch,  under  the  name 
of  tuberculin.  The  theory  of  this  method  of  treatment  is  that  it  increases 
the  reaction  of  the  body  to  the  invasion  of  the  micro-organism,  leading 
thus  to  its  destruction.  While  a  number  of  authorities,  notably  Von 
Ruck,1  believe  that  the  use  of  tuberculin,  in  conjunction  with  other 
methods  of  treatment,  gives  better  results  than  can  be  obtained  without 
it,  it  certainly  cannot  be  regarded  in  any  sense  as  a  cure.  It  is  largely 
used  as  a  diagnostic  measure  by  the  veterinarian,  and  occasionally  in 
human  medicine.  When  tuberculin — that  is,  tubercular  toxin — is  in- 
jected into  the  blood  in  certain  small  quantity,  it  produces  no  febrile 
reaction  in  the  normal  individual  because  there  is  not  enough  of  it  present 
in  the  system.  If,  however,  the  injected  toxin  be  added  to  a  toxin  which 
has  been  previously  produced  in  the  body,  and  which  is  already  in  the 
blood,  the  aggregate  amount  will  be  capable  of  producing  a  hectic  fever, 
which  will  demonstrate  the  existence  of  a  toxin-producing  focus  in  the 
body, — i.e.,  of  tuberculosis. 

The  toxin  produced  by  the  streptococci  was  at  one  time  largely  used  in 
the  treatment  of  cancer,  but  the  clinical  results  have  been  such  that  the 
procedure  has  been  almost  abandoned. 

SERUM  ANTIDIPHTHERICUM.  U.  S.  Antidiphtheric  Serum. — 
Diphtheria  Antitoxin. — The  U.  S.  Pharmacopoeia  requires  that  the 
.antidiphtheritic  serum  shall  be  of  the  standard  strength  established  by 
the  U.  S.  Marine  Hospital  Service,  and  it  should  always  be  freshly  pre- 
pared, as  even  when  preserved  in  the  best  manner  it  gradually  loses  its 
power,  the  annual  loss  varying  from  ten  to  thirty  per  cent.  Although  the 
abundant  clinical  evidence  appears  to  demonstrate  beyond  all  doubt  that 
diphtheria  antitoxin  is  an  absolute  specific  in  diphtheria,  it  is  essential 
that  it  be  used  early,  as  it  acts  chiefly  by  arresting  the  growth  of 
the  bacilli.  If  the  antitoxin  be  given  late  in  the  disorder  it  may  arrest  the 
further  growth  of  the  germ,  but  the  patient  may  die,  nevertheless,  because 
the  tissues  are  already  fatally  poisoned  with  the  toxin,  or,  perchance,  have 
already  undergone  an  irreparable  degeneration.  Again,  there  is  in  every 
bad  case  of  diphtheria  after  the  first  twenty-four  hours  a  general  septic 
infection :  so  soon  as  lodgement  has  been  fairly  effected  by  the  Loffler 
bacillus,  and  local  tissue-change  set  in,  streptococci  and  other  septic  germs 
begin  to  develop  rapidly  in  the  dying  tissues,  and  very  soon  give  origin 
to  a  general  septic  infection,  which  in  most  fatal  cases  of  diphtheria  is  an 
important  factor  in  the  causation  of  death.  Evidently  a  Loffler  bacillus 
antitoxin  is  useless  against  a  streptococcus  toxin. 

The  absolute  importance  of  the  early  use  of  the  antitoxin  during 

35 


546  .GENERAL   REMEDIES. 

diphtheria  is  very  evident.  There  are  very  few,  if  any,  well-observed 
cases  of  diphtheria  on  record  in  which  it  has  been  positively  determined 
that  the  antitoxin,  administered  during  the  first  few  hours  after  the  out- 
break of  the  disease,  has  failed  to  bring  about  a  cure.  On  the  other 
hand,  statistics  seem  to  show  that  if  the  injection  be  postponed  to  the 
fifth  day,  the  mortality-rate  is  not  reduced  by  the  use  of  antitoxin.  Our 
modern  municipal  scientific  methods,  notwithstanding  all  their  laudations, 
are  liable  to  become  causes  of  death.  A  case  of  suspected  diphtheria 
presents  itself  to  the  practitioner  ;  already  the  child  has  been  sick,  it  may 
be,  one  or  two  days.  A  culture-tube  is  prepared,  sent  to  the  municipal 
laboratory,  examined,  and  the  result  sent  back  to  the  practitioner,  who 
then  goes  to  see  the  patient.  It  is  very  fortunate  if  not  more  than  one 
day  is  lost  in  this  way,  and  the  loss  of  those  hours  may  well  mean  the 
loss  of  the  life,  for  the  time  has  elapsed  during  which  the  antitoxin  would 
best  act.  There  is  no  reason  at  present  for  believing  that  the  antitoxin 
used  in  moderate  quantity  does  harm  when  the  child  has  not  diphtheria. 
When,  therefore,  any  case  presents  the  clinical  aspect  of  diphtheria  the 
antitoxin  should  be  used  at  once.  For  educational  purposes,  and  for 
rendering  definite  our  knowledge,  the  municipal  laboratories  are  very 
useful ;  for  purposes  of  treatment  the  less  attention  paid  to  them  probably 
the  better  for  the  patients. 

The  use  of  antitoxin  in  any  case  of  diphtheria  should  not  interfere 
with  the  usual  local  and  general  treatment. 

As  it  is  never  possible  in  any  case  of  human  diphtheria  to  know  how 
much  of  the  toxin  is  in  the  system,  exact  antitoxin  dosage  is  impossible, 
but  some  general  working  rule  must  be  formed,  especially  as  there  are  a 
large  number  of  serums  upon  the  market  of  varying  strength.  Universal 
consent  now  seems  to  have  been  given  to  the  recognition  of  Behring's 
antitoxin  unit,  which  is  one  cubic  centimeter  of  an  antitoxin  serum  of  such 
strength  that  this  amount  of  it  is  capable  of  overcoming  ten  times  the 
minimum  fatal  dose  of  the  toxin  for  the  gunea-pig.  The  antitoxin  solu- 
tion should  be  injected  deeply  into  the  buttocks  or  back  with  every  pos- 
sible antiseptic  precaution.* 

The  greatest  danger  after  that  of  not  using  diphtheria  antitoxin  early 
enough  is  that  it  be  not  given  freely  enough.  The  ordinary  dose  of  diph- 
theria antitoxin  for  an  adult  is  from  two  thousand  to  five  thousand  units, 
according  to  the  severity  of  the  case.  In  very  virulent  cases,  however, 
it  may  be  advisable  to  exceed  this  dose,  since  frequently  when  the 
ordinary  quantity  fails  a  dose  of  ten  thousand  to  twelve  thousand  units 
proves  efficacious.  Since  the  injections  are  practically  harmless,  it  seems 
better  to  err  on  the  side  of  too  large  than  too  small  dosage,  although 
Musser 2  has  recommended  the  use  of  comparatively  small  doses  of  five 
hundred  to  one  thousand  units  repeated  at  frequent  intervals  every  six 
hours. 


*  After  an  especially  dangerous  exposure  to  diphtheria,  the  antitoxin  may  be  em- 
ployed as  a  prophylactic,  in  doses  of  from  two  hundred  to  five  hundred  units. 


ALTERATIVES.  547 

It  is  affirmed  that  the  milder  method  is  less  apt  to  be  followed  by  dis- 
agreeable antitoxin  symptoms  ;  but  as  these  disagreeable  symptoms  are 
of  little  importance,  the  superior  promptness  and  certainty  and  the 
avoidance  of  frequent  disturbance  of  the  patient,  which  attend  the  more 
heroic  method,  seem  to  us  to  make  it  preferable. 

The  dose  of  antitoxin  for  children  should  be  proportionately  much 
larger  than  in  adults,  and  the  American  Pediatrical  Society  recommends 
that  in  children  over  two  years  of  age,  in  cases  of  moderate  severity,  from 
fifteen  hundred  to  two  thousand  units  should  form  the  initial  dose  ;  in 
children  under  two  years,  quantities  up  to  one  thousand  units  may  be 
given. 

In  most  cases  the  injection  of  the  antitoxin  is  followed  in  a  very  few 
hours  by  a  fall  of  temperature  and  a  decrease  of  the  local  diphtheritic 
symptoms.  Occasionally,  but  not  usually,  this  amelioration  is  preceded 
by  a  temporary  rise  of  temperature.  Sometimes  the  disagreeable  symp- 
toms produced  by  the  injection  appear  in  a  few  hours  ;  perhaps  more 
commonly  they  are  not  developed  until  from  six  to  nine  days  ;  and  it  is  even 
affirmed  that  they  may  be  delayed  to  nine  weeks,  and  that  they  have  led 
to  the  mistaken  diagnosis  of  scarlet  fever  or  other  exanthema.  The  char- 
acteristic symptoms  are  rise  of  temperature,  with  eruption  upon  the  skin, 
and  rarely  swelling  and  pain  in  the  joints.  The  skin  eruption  may  be 
purely  erythematous,  is  often  scarlatinoid,  and  perhaps  as  frequently 
rubeoloid,  and  sometimes  it  takes  the  form  of  a  severe  urticaria.  There 
is  evidence  to  show  that  these  after-effects  follow  much  more  frequently 
upon  the  use  of  diluted  antitoxin  than  after  injections  of  concentrated 
serums,  and  it  seems  to  us  probable  that  they  are  produced  in  some  way 
by  the  serum  itself  and  not  by  the  antitoxin. 

Tetanus. — Despite  the  vigorous  claims  of  various  scientific  authori- 
ties concerning  the  value  of  tetanus  antitoxin,  the  results  with  this  method 
of  treatment  have  not  been  very  brilliant.  Goodrich,*  in  a  collection  of 
two  hundred  and  twenty-six  reported  cases,  found  that  sixty-four  per  cent, 
of  those  treated  by  other  methods  recovered,  and  only  sixty-three  per 
cent,  of  those  treated  by  antitoxin.  The  published  mortality  of  other 
authors  who  have  employed  tetanus  antitoxin  varies  from  thirty-five  to 
sixty  per  cent. 

In  the  laboratory,  tetanus  in  the  lower  animals  can  be  cured  with 
almost  absolute  certainty  by  the  proper  use  of  antitoxin.  The  causes 
of  the  discrepancy  between  laboratory  and  practical  results  have  been 
pointed  out  by  Tsuzuki.4  This  author  found  that  tetanus  antitoxin  was 
capable  of  saving  mice  only  when  the  dose  of  the  toxin  was  not  more  than 
two  or  three  times  the  minimum  fatal  dose,  and  when  the  antitoxin  was 
injected  within  six  hours  after  the  administration  of  the  toxin.  He  further 
found  that  the  antitoxin  had  much  more  effect  if  injected  in  the  neighbor- 
hood of  the  inoculation  with  the  toxin  than  when  administered  subcuta- 
neously  in  another  part  of  the  body. 

It  is  very  evident  from  these  results  that,  in  cases  of  human  tetanus, 


548  GENERAL    REMEDIES. 

where  the  virulence  of  the  infection  is  unknown  and  where  there  is  usually 
a  considerable  amount  of  toxin  in  the  system  before  the  outbreak  of  the 
symptoms,  tetanus  antitoxin  cannot  be  expected  to  rank  as  an  infallible 
cure  for  this  disease.  Nevertheless,  especially  in  those  cases  which  are 
seen  early,  the  immediate  use  of  antitoxin,  since  it  need  not  interfere  with 
other  methods  of  treatment,  appears  to  be  advisable. 

Unfortunately,  the  unit  of  dose  for  the  tetanus  antitoxin  does  not  seem 
fully  established.  Behring 5  has  prepared  a  toxin  of  such  power  that  one 
cubic  centimetre  will  kill  in  from  four  to  five  days  four  million  grammes 
of  living  tissue.  Behring' s  unit  for  tetanus  antitoxin  is  the  amount  suffi- 
cient to  neutralize  ten  cubic  centimetres  of  this  test-toxin.  The  dose, 
according  to  Behring,  should  be  at  least  one  hundred  units  (ten  cubic 
centimetres  of  Behring' s  serum).  Tizzoni  has  very  strenuously  objected 
to  Behring' s  conclusions. 

Streptococcus  Infections. — The  streptococcus  antitoxin  has  been  recom- 
mended in  the  treatment  of  erysipelas,  puerperal  septic&mia,  and  similar 
conditions.  The  reports  of  the  results,  however,  do  not  seem  to  be  very 
encouraging.  In  three  hundred  and  fifty  cases  collected  by  the  American 
Gynaecological  Society,  the  mortality  in  puerperal  sepsis  treated  with 
streptococcus  antitoxin  was  thirty-three  per  cent. ,  which  is  no  less  than 
the  ordinary  mortality  rate  in  these  cases.  It  is  evident  that  a  strepto- 
coccus antitoxin  can  prove  of  no  value  in  staphylococcus  infections. 
Streptococcus  antitoxin  has  also  been  used  in  the  treatment  of  secondary 
infections  with  the  streptococcus  occurring  in  diphtheria  and  scarlet  fever. 
There  is  no  generally  recognized  unit  of  streptococcus  antitoxin,  and 
therefore  cannot  be  any  definite  dosage  ;  so  that  the  practitioner  can  only 
follow  the  directions  given  with  the  antitoxin  serum  by  the  manufacturing 
firm. 

Cholera. — Lazarus  discovered  that  the  blood-serum  of  human  beings 
who  have  recovered  from  an  attack  of  Asiatic  cholera  possesses  proper- 
ties which  render  it  capable  of  protecting  animals  from  fatal  doses  of  the 
spirillum  of  Asiatic  cholera.  He  regarded  this  substance  as  being  of  the 
nature  of  an  antitoxin,  and  the  protective  action  of  the  human  serum  as  sim- 
ilar to  the  antitoxin  of  diphtheria,  tetanus,  etc.  The  studies  of  R.  Pfeiffer, 
however,  have  shown  that  the  principle  contained  within  the  blood-serum 
is  not  of  the  nature  of  an  antitoxin,  but  is  bactericidal  ;  it  acts  by  causing 
rapid  disintegration  of  the  introduced  cholera  organism,  and  thus  pre- 
vents the  rapid  multiplication  that  brings  about  the  death  of  the  exposed 
animal.  A  few  minutes  after  the  simultaneous  introduction  of  the  cholera 
vibrio  and  of  the  blood-serum  into  the  peritoneal  cavity  of  small  animals, 
such  as  the  guinea-pig,  the  micro-organisms  begin  to  disintegrate,  and 
very  soon  they  are  completely  destroyed, 

Pfeiffer  also  showed  that  dead  cholera  organisms  are  still  toxic  and 
capable  of  acting  similarly  to  the  living  germs.  Haffkin  has  applied 
this  method  to  the  immunization  of  human  beings  to  cholera  ;  he  cul- 
tivates the  germ  in  bouillon,  and  after  a  certain  growth  has  been  ob- 


ALTERATIVES.  549 

tained,  heats  sufficiently  to  kill  the  germ  without  completely  destroying  the 
cholera  poison  which  adheres  to  its  body,  and  which  is  a  very  sensi- 
tive substance.  Injections  of  such  cultures  in  human  beings  are  followed 
by  a  local  reaction  and  febrile  movements  and  the  appearance  of  a  pro- 
tective substance  in  the  blood-serum  in  man  similar  to  that  present  after 
an  attack  of  the  disease.  Two  injections  are  commonly  made  at  the 
interval  of  about  a  week,  after  which  the  protection  of  the  individual  is 
believed  to  be  complete.  This  method  has  been  applied  on  a  large  scale 
in  India,  and  apparently  with  a  measure  of  success. 

Hay- Fever. — Dunbar's  Hay  Fever  Antitoxin  is  at  present  obtained  by 
inocculating  healthy  horses  with  a  toxin  obtained  from  the  pollen  of  cer- 
tain flowering  grasses  and  plants.  Dunbar  in  1903  isolated  from  the 
pollen  an  active  toxin  the  exact  nature  of  which  he  could  not  determine 
further  than  saying  it  was  a  toxalbumin.  Hay-fever  patients  showed  a 
marked  reaction  to  this  toxin,  at  any  time  of  the  year,  if  it  was  brought  in 
contact  with  the  mucous  membrane  or  injected  subcutaneously  and  these 
attacks  were  instantly  relieved  by  the  application  of  the  antitoxin. 

When  Dunbar's  antitoxin  was  first  used  in  America,  the  reported  re- 
sults by  Mayer,  McCoy  and  others  were  so  favorable  that  the  use  of  the 
treatment  rapidly  spread.  In  the  year  1904,  the  results  obtained  were 
not  so  favorable  and  the  use  of  the  antitoxin  rapidly  sank  in  popular- 
ity. This  difference  in  results  is  probably  dependant  on  the  difference 
between  European  hay-fever  which  occurs  in  the  early  summer  and  the 
American  type  which  occurs  in  the  late  Summer  or  early  Fall.  The  first 
cases  in  this  country  were  treated  by  an  antitoxin  especially  prepared  by 
Dunbar  and  his  assistants  from  ragweed  pollen  and  sent  to  a  few  well 
known  specialists.  In  the  summer  of  1904  the  product  obtained  was  that 
produced  by  Schimmell  &  Co. ,  from  flowering  grasses  and  was  used  pro- 
miscuously without  attention  to  detail.  From  the  results  of  1903  and 
1904,  it  seems  that  in  America  the  antitoxin  to  be  of  any  value  must  be 
prepared  from  the  pollen  of  goldenrod,  ragweed  or  one  of  the  toxic  plants 
which  bloom  late  in  the  summer.  In  exceptional  cases  of  mild  hay-fever, 
frequently  called  rose  cold,  the  antitoxin  prepared  from  the  grasses  is 
more  efficient.  The  results  of  the  summer  of  1905  confirm  this  assump- 
tion and  since  the  antitoxin  prepared  by  Schimmell  &  Company  was  put 
on  the  market  and  given  more  attention  to  the  treatment  in  details,  the 
results  were  very  favorable. 

The  present  status  of  the  antitoxin  treatment  of  hay  fever  is  that  in 
the  majority  of  cases  of  true  hay  fever  in  which  the  attack  begins  about 
the  second  week  in  August,  the  careful  use  of  the  antitoxin  will  give  more 
or  less  benefit.  To  obtain  the  greatest  relief  the  treatment  should  begin 
4  or  5  days  before  the  expected  attack  and  keep  up  regularly  throughout 
the  whole  hay-fever  season.  References  to  the  literature  may  be  found 
in  the  article  of  H.  W.  Loeb.8 

Bubonic  Plague. — Pest. — The  discovery  by  Yersin,  in  1894,  of  the 
bacillus  of  the  bubonic  plague  has  caused  protective  measures  to  be 


550  GENERAL  REMEDIES. 

employed  in  combating  that  disease.  Several  methods  are  now  in  use  ; 
that  of  Yersin  consists  in  the  immunization  of  horses  or  other  large  ani- 
mals to  injections  of  the  plague  bacillus,  and  the  use  of  the  blood-serum 
obtained  from  these  animals  in  a  manner  similar  to  the  employment  of  the 
antitoxin  of  diphtheria. 

Haffkin's  method,  which  has  been  used  on  a  larger  scale,  and  ap- 
parently with  less  doubtful  results  than  that  of  Yersin,  is  in  principle 
similar  to  the  protective  inoculation  for  cholera.  Bouillon  cultures  of 
the  plague  bacillus  (the  organisms  being  obtained  directly  from  human 
cases  of  the  plague)  are  incubated  for  about  two  weeks.  The  bouillon 
is  finally  heated  to  60°  C. ,  for  about  twenty  minutes,  in  order  to  kill  the 
bacillus,  after  which  half  of  one  per  cent,  of  carbolic  acid  is  added  in  order 
to  preserve  the  serum  from  accidental  contamination  by  micro-organisms. 
The  injections  are  made  into  the  soft  tissues  of  the  thigh,  the  entire 
culture  being  used.  Two  injections  are  usually  employed,  at  intervals  of 
six  days.  The  symptoms  are  elevation  of  temperature  and  swelling  about 
the  point  of  inoculation,  most  marked  after  the  first  injection.  The  sec- 
ond inoculation  is  believed  to  give  protection.  The  statistics  gathered 
from  India,  where  the  plague  has  prevailed,  are  highly  encouraging  as  to 
the  value  of  this  procedure.  The  serum  is  of  no  use  in  the  treatment  of 
developed  cases  of  the  plague. 

Another  method  of  protection  which  is  being  employed  is  that  of 
Lustig,  who  produces  from  the  dead  plague  bacillus,  by  treatment  with 
acids  and  then  alkalies,  a  nucleo-proteid,  whose  inoculation  into  animals 
and  human  beings  gives  active  immunity  to  the  plague  organism.  The 
blood-serum  from  animals  so  immunized  may  be  used  in  the  treatment  of 
the  developed  plague  ;  or,  injected  into  healthy  human  beings,  affords  a 
passive  immunity  which,  however,  endures  only  a  few  weeks.  It  is, 
therefore,  capable  of  use  in  protecting  for  a  short  time  a  community 
exposed  to  the  plague,  although  less  reliable  than  Haffkin's  serum.  Its 
advantage  is  that  it  affords  immediate  protection,  whereas  the  other  means 
employed  require  a  number  of  doses  before  the  protective  action  appears. 

The  blood-serum  of  human  beings  and  animals  who  have  withstood 
injections  of  the  plague  bacillus  possesses  agglutinating  properties  for  the 
plague  organisms  ;  this  agglutination,  however,  does  not  appear  early  in 
the  infection,  but  is  a  phenomenon  of  the  convalescence.  Its  usefulness, 
therefore,  in  the  diagnosis  of  the  plague  is  somewhat  doubtful. 

Snake-poisoning. — Sewall  appears  to  have  been  the  first  to  demonstrate 
the  possibility  of  producing  immunization  against  the  venom  of  serpents, 
having  proved  as  long  ago  as  1887  that  it  was  possible  by  a  series  of  in- 
oculations of  increasing  intensity  temporarily  to  immunize  pigeons  against 
the  rattlesnake-poison. 

The  serum  of  the  blood  of  the  artificially  immunized  animal  has  been 
found  to  be  of  remedial  value  in  snake-poisoning,  and  has  been  put  upon 
the  market  commercially.  Its  use  as  a  prophylactic  is  justifiable  only  in 
certain  conditions  when  there  is  about  to  be  an  extraordinary  exposure  to 


ALTERATIVES.  551 

a  possible  snake-bite,  since  the  immunity  it  confers  lasts  only  for  a  short 
time.  The  value  of  the  serum  as  a  curative  agent  has,  however,  been 
proven  not  only  in  the  laboratory  but  also  in  a  number  of  recorded  cases 
of  snake-bite  ;  so  that  it  should  be  carried  by  those  whose  duties  or 
desires  lead  them  into  tropical  countries  where  poisonous  serpents  abound. 

Antitoxin  for  snake-venom,  suggested  almost  simultaneously  by  Phisalix  and 
Bertrand,1  and  Calmette,2  was  first  practically  prepared  by  Calmette.  As  was  origi- 
nally shown  by  Mitchell  and  Reichert,3  snake-venom  contains  two  toxic  substances — 
a  local  and  a  constitutional  poison.  The  serum  of  Calmette  is  prepared  from  cobra- 
venom,  which  contains  comparatively  little  of  the  local  irritant,  and,  according  to 
McFarland,*  immunizes  only  against  the  generally  acting  element  of  snake- 
venoms.  Poisons  of  the  American  snakes,  such  as  the  rattlesnake,  the  moccasin, 
etc.,  are  mostly  highly  irritating  venenes.  In  an  effort  to  produce  an  antitoxin 
which  would  be  efficacious  against  these  serpents,  McFarland  was  unsuccessful  in 
producing  an  immunity  in  the  horse  to  the  local  irritant  action  of  the  poison,  although 
he  obtained  a  serum  which  overcame  the  constitutional  effect  of  these  venoms. 
Although  Calmette  claims  that  his  antitoxin  is  efficacious  not  only  against  various 
serpent-poisons,  but  against  scorpion-bites,  McFarland  has  shown  that  although  it 
destroys  the  nerve-depressant  poison  it  does  not  overcome  the  effects  of  a  great 
local  irritation  which  is  caused  by  such  venoms  as  rattlesnake-poisoning,  and  is  not 
a  certainly  life-saving  remedy.  More  recently  Noguchi 5  has  succeeded  in  obtaining 
a  rattlesnake  antivenin.  Fraser6  asserts,  however,  that  the  dose  of  antivenin 
required  to  afford  an  efficient  degree  of  immunity  is  so  large  as  to  make  it  imprac- 
ticable in  human  poisoning.  He  claims  that  350  c.c.  are  necessary  to  cure  a  man  of 
one  hundred  and  seventy  pounds  weight ;  the  ordinary  quantity  recommended  is  15 
to  20  c.c.  . 

As  the  result  of  experiments  by  various  observers,  it  has  been  estab- 
lished that  venomous  serpents  are  poisoned  by  snake-venom  only  with 
the  greatest  difficulty  ;  that  the  ordinary  non-poisonous  snakes  share 
this  immunity  to  a  distinctly  less  degree  ;  and  that  certain  of  the  higher 
animals,  notably  the  mongoose,  are  distinctly  resistant  to  the  poison.  It 
is  probable  that  the  immunity  in  the  higher  animals  is  an  inherited, 
' '  acquired  character, ' '  due  to  the  repeated  survival  of  generations  of  bit- 
ten animals,  the  immunity  of  the  individual  being  partially  transmitted 
to  the  offspring. 

According  to  the  reports  of  missionaries,  the  various  compounds 
prepared  by  the  ' '  witches ' '  in  Africa  for  the  cure  of  snake-bite  have  the 
liver  of  the  serpent  in  their  combination  ;  and  T.  R.  Fraser,  of  Edin- 
burgh, has  experimentally  proved  that  the  bile  of  poisonous  serpents  is  a 
very  active  antidote  to  the  poison,  neutralizing  the  venom  when  mixed 
with  it  in  equal  quantities.  Even  the  bile  of  ordinary  snakes  has  a 
feeble  antidotal  power.  When  after  a  bite  it  is  possible  to  kill  the  snake, 
all  of  its  bile  should  be  injected  into  the  immediate  neighborhood  of  the 
wound. 

LECITHIN. 

Lecithin  is  a  complex  fatty  body  representing  the  phosphorus-holding  molecule 
of  the  central  nervous  system.  It  occurs,  however,  not  only  in  the  higher  animals 
but  in  many  of  the  food-stuffs,  and  is  especially  abundant  in  embryonal  tissues,  as 


552  GENERAL   REMEDIES. 

eggs  and  seeds.  There  are  several  varieties  of  lecithin  so  that  the  lecithin  of  eggs, 
for  example,  is  not  chemically  the  same  as  that  found  in  the  human  nervous  system. 
The  human  lecithin  is  a  di-stearyl-glycerophosphate  of  cholin,  but  any  other  fatty 
acid  as  oleic  or  palmitic,  may  be  substituted  for  the  stearic  ;  thus  we  may  have  a 
palmityl  or  an  oleyl  lecithin.  It  is  not  probable  that  there  is  any  marked  difference 
in  the  physiological  properties  of  the  different  forms  of  lecithin. 

Lecithin  occurs  a  yellowish,  waxlike  substance,  soluble  in  ether  and  alcohol. 
In  water  it  swells  up  and  forms  a  sort  of  emulsion  but  strictly  speaking  is  not  dis- 
solved. 

PHYSIOLOGICAL  ACTION. — It  has  been  shown  by  H.  C.  Wood,  Jr.,1  that  lecithin 
is  non-toxic,  and,  unless  injected  in  enormous  quantities,  has  practically  no  physi- 
ological action.  Amounts  equivalent  to  0.2  gramme  per  kilo  somewhat  slow  the 
respiration  and  pulse,  but  do  not  materially  alter  the  blood-pressure. 

Lecithin  is  unstable  and  easily  decomposed  into  its  component  parts,  one  of 
which,  choline,  is  poisonous.  Choline  is  closely  related  to  the  actively  toxic  sub- 
stance, neurine.  These  poisonous  principles  seem  to  be  in  the  nature  of  alkaloids. 
Their  toxic  effects  consist  principally  in  paralysis  of  the  respiration,  of  the  peripheral 
motor  nerves  and  of  the  spinal  cord,  stimulation  of  the  peripheral  ends  of  the  pneu- 
mogastric  nerve,  and  temporary  rise  of  the  blood-pressure  followed  by  a  fall,  which 
with  toxic  doses  brings  it  below  normal. 

Danilewsky "  found  that  pups,  to  which  were  administered  lecithin,  increased 
in  weight  more  rapidty  than  did  the  control  animals,  and  that  there  was  an  augmen- 
tation in  the  number  of  red  blood-cells  without,  however,  a  corresponding  increase 
in  the  percentage  of  haemoglobin.  Serono  *  obtained  a  similar  result  in  studies  made 
upon  human  beings,  and  also  determined  greater  elimination  of  urea,  despite  which 
fact  there  was  a  gain  in  weight.  This  increase  in  the  weight  is  probably  attributable, 
as  Serono  points  out,  to  a  stimulation  in  cellular  reproduction  brought  about 
through  the  excess  of  protoplasmic  phosphorus  in  the  parent  cell. 

THERAPEUTICS. — Claude  and  Zaky 4  and  Gilbert  and  Fournier5  have  employed 
lecithin  in  tuberculosis,  with  resulting  gain  in  weight.  Serono  finds  it  of  some  value 
in  chlorosis,  but  less  active  than  the  iron  salts.  Lancereaux  and  Paulesco6  em- 
ployed it  in  two  cases  of  pancreatic  diabetes  with  gain  in  weight  and  diminution  in 
the  amount  of  sugar.  The  dose  is  from  0.1-0.3  gramme  (1-5  grains).  It  was  at 
first  used  hypodermically  because  of  the  fear  that  it  would  be  broken  up  by  the  di- 
gestive juices  into  its  component  parts  the  remedial  of  which  is  very  doubtful. 
Danilewsky  and  Gilbert  and  Founier  assert,  however,  that  it  acts  when  given  by 
the  mouth  as  well  as  when  given  hypodermically,  although  it  must  be  administered 
in  larger  doses. 


ALTERATIVES. 


553 


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xxvii. 

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CACODYLIC  ACID. 

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2.  LIEGEOIS    ....  Gaz.  des  Hop.,  1869. 

3.  KEYES A.  J.  M.  S.,  Jan.  1876. 

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5.  GAILLARD   ....  A.  G.  M.,  Nov.  1885. 

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478. 

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Syph.,  xi.  no. 

16.  SILVA C.  K.  M.,  1888,  ix. 


554 


GENERAL   REMEDIES. 


REFERENCES.- 

17.  KLEMPERER  .  .   .  V.  A.  P.  A.,  1889,  cxviii.  3. 

18.  YIRCHOVV    .  .   .   .  B.  K.  W.,  1888,  xxv.  4. 

19.  LENTERT    ....  Fort.  M.,  1895,  xiii.  5. 

20.  PREVOST     .   .  .   .  R.  M.  S.  R.,  1882-83.  6- 

21.  BINET R.  M.  S.  R.,  1891.  7. 

22.  VON  BOECK    .   .   .  S.  Jb.,  cxlv.  8. 

23.  SCHRODER  .  .   .   .In.  Dis.,  Wiirzburg,  1893.  9. 

24.  GUTTENBERG  and  GURBER  .  M.  M.  W.,  1895, 

xlii.  10. 

25.  HELLER Charite  Annal.,  1895,  xx.  n. 

26.  MIALHE Chimie  Applique'e.  12. 

27.  JEANNEL S.  Jb.,  cxliii.  9.  13- 

28.  ARNOZAN    ....  Journ.  de  Bordeaux,  Dec  14. 

1883.  15 

S.  Jb.,  cxliii.  9.  16. 

M.  News,  xliii.  682.  17- 

Guy  H.  R.,x.  35.  18. 
Amer.  Med.,  1902,  iv. 


ROSENBACH 
McPHEDRAN 


>9 

3°. 
31- 

32.  WOOD,  JR.  . 

33 


MAX  and  SORGE  .  Vierteljahrs,    f.    gericht. 
Med.  1905,  xxix.  85. 

IODIPIN. 

.    \VlNTERNITZ       .     .  M.  M.  W.,  1903. 

.  SCHUSTER  ....  W.  M.  P.,  1901,  xlii. 
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IODINE. 

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,  HARNACK   .  .  .  .  B.  K.  W.,  1882. 

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Soc.    Erlangen,    1894-98, 

26-30. 
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Derm.,  1873. 

SEE L.  M.  R.,  i.  777. 

,  EHLERS Ann.  de  Derm,  et  Syph., 

1890. 
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lehre,  Berlin,  1870,  252. 
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114. 
TROUSSEAU    .   .   .  B.  A.  R.  B.,  xxv. 

WOLF B.  K.  W.,  1886,  580. 

KAMMERER    .   .   .  V.  A.  P.  A.,lix.  467,  Ix.  527. 

ROSE V.  A.  P.  A.,  xxxv. 

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ZEISSL Z.  K.  M.,  xxvii. 

ZEISSL Wien.   Med.   Presse,   1898, 

xxxix. 

PREVOST  and  BINET  .  R.  M.  S.  R.,  1890. 
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JONES Beale's  Archives,  i. 

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HAIG L.  L.,  1893,  i. 

DA  COSTA  .  .   .  .  A.  J.  M.  S.,  Jan.  1875. 

SQUIER M.  News,  1891,  lix. 

WALLACE   .   .   .   .  Liverpool  Med.  Surg. Rep., 

1871. 
MARSHALL    .  .  .  T.  G.,  Feb.  1888. 

ANTEN A.  E.  P.  P.,  1902,  xlviii. 

LESSER A.  D.  S.,  1903,  Ixiv. 

STOCKMAN  and  CHARTERIS  .  B.  M.  J.,  1901,  ii. 

BESNIER B.  M.  S.  H.,  xx. 

BJELOGOLOWY  .   .  A.  V.  K.,  Bd.  x. 

IODOFORM. 

ZELLER Z.  P.  C.,  viii.  70. 

HOYGES A.  E.  P.  P.,  x.  405. 


-  Continued. 

RUMMO A.  de  P.,  1883,  144. 

FLOUCAUD  ....  Thesis,  Montpellier,  1872. 

KREVET Th.  M.,  1888,  ii. 

KRONACHER  .  .   .  M.  M.  W.,  1887,  xxxiv.  546. 

LUBERT Fort.  M.,  v.  343. 

HEYN  and  DROVSING  .  Fort.  M.,  v.  33. 

OLSEN Norsk    Mag.    for    Legevi- 

densk,  1886. 

KONIGE Th.  M.,  April,  1887. 

SATTLER     ....  Fort.  M.,  v.  362. 

BRUNS Th.  M.,  May,  1887. 

ELSBERG     ....  P.  M.T.,  1873,  iv.  4. 
LANGENSTEIN  .  .  W.  M.  W.,  1882,  xxxii.  1051. 

5.  CZERNY W.  M.  W.,  1882,  xxxii.  180. 

SAMTER  and  RETZLAFF  .  T.  G.,  1889. 

ROBERT A.  I.  P.  T.,  1901,  viii. 

ANSCHUTZ  .  .   .   .  B.  K.  C.,  1900,  xxviii.  233. 

IODOL. 
MAZZONI     .  .   .   .  B.  K.  W.,  1885. 

MARCUS B.  K.  W.,  1886. 

PAH  i In.  Dis.,  Berlin,  1886. 

LANGENSTEIN  .  .  T.  G.,  1887,  768. 

PICK Viertelj.  f.  Derm.  u.  Syph., 

1886. 
CERVESATO    .   .   .  B.  K.  W.,  1889,  xxvi. 

ARISTOL. 

NEISSER B.  K.  W.,  1890,  xix. 

QUINQUAUD  and  FOURNIOUX  .  C.   R.  S.   B. 
1890. 

THIOSINAMINE. 
VON  HEBRA  .  .  .  M.  P.  D.,  1893,  ix. 
SUKER M.  A.,  1902. 

COD-LIVER  OIL. 
CAMPBELL  ....  Brit,  and   For.  Med.-Chir. 

Rev.,  1856,  xvii.  21. 
NAUMANN  ....  A.  Hk.,  1865,  536. 

BERTHE L'Union  M6d.,  1856,  x. 

BUCHHEIM  .   .   .   .  A.  E.  P.  P.,  iii. 

GAD A.  A.  P.,  1878. 

HARE B.  M.  S.  J.,  cxvi.  279. 

RANDOLPH  and  ROUSSEL  .  P.  M.  T.,  xiv.  239. 
BOUILLOT   ....  Compt.-Rend.  Acad.  Sci., 

1892,  cxv. 


CALCIUM 

CHOSSAT 

ROLOFF    

HAUBNER    .  .   .  . 

VOIT     

HEGAR 

BOKER  

PERL 

RIESELL  . 


9.  TEISSIER 


DUSART   

PlORRY      . 


12.    BODDAERT  .     . 


PHOSPHATE. 

C.  R.  A.  S.,  xiv. 

V.  A.  P.  A.,  xlvi.  302. 

S.  Jb.,  cli.  138. 

Z.  Bi.,  xvi.  198. 

S.  Jb.,  cli. 

S.  Jb.,  cli. 

V.  A.  P.  A.,  lxxiv«54. 

Hoppe  -  Seyler's       Med.- 

Chem.  Untersuch.,  318. 
Le  Mouvement  M6d.,  Sept. 

1875- 

A.  G.  M.,  6  s.,  xv. 
Journ.     de    Chim.    Med., 

1863,  ix. 
A.  Pharm.,  1895,  ii. 


COLCHICUM. 

ALBERS D.  Kl.,  1856,  xxxvi. 

ROSSBACH  ....  Pharmak.  Untersuch.,  ii. 

FERRER U.  M.  M.,  i. 

PASCHKIS    .       .   .  S.  Jb.,  cci.  232. 


ALTERATIVES. 


555 


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-15- 


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THYROID  BODY. 
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GOTTLIEB    .   .   .   .  D.  M.  W.,  1896,  xxii. 

WORMSER  .   .   .   .  A.  G.  P.,  Ixvii.  505. 

Roos     ......  M.  M.  W.,  1896,  xliii. 

LEVY    ......  D.  M.  W.,  1896. 

HILDEBRANDT  .   .  B.  K.  W.,  1896,  xxxiii. 
BAUMANV  and  GOLDMANN  .  M.  M.  W.,  1896. 
FRANKEL    ....  Aertzl.  Central.  Anzeiger, 

1895- 

HUTCHINSON    .   .  B.  M.  J.,  1896,  i. 
BALLET  and  ENRIQUEZ  .  Med.  Mod.,  1895,  vi. 
HERTOGHE    .  .   .  B.  A.  R.  B.,  1896. 
VAMOSSY  and  VAS  .  M.  M.  W.,  1897,  xliv. 
HASKOVEC     .   .   .  W.  M.  B.,  1895,  xviii.  ;  A. 

I.  P.  T.,  1901,  viii.  167. 
OLIVER  and  SCHAFER  .  J.  P.,  1895. 
OTT  .......  Med.  Bull.,  1898,  xx.  89. 

BELL     ......  Phys.  and  Surg.,  1898,  xx. 

3°9- 
PERRY  ......  N.  Y.  M.  R.,  1896. 


18.  MOSKLY M.  News,  1898,  Ixxii.  353. 

19.  SCHOLZ Centralbl.  f.  innere  Med., 

1895,  104. 

20.  RICHTER     ....  Centralbl.  f.  innere  Med., 

1896,  65. 

21.  MAYER D.  M.  W.,  1896,  xxii. 

22.  Roos Z.  P.  C.,  1896,  xxi. 

23.  GLUZINSKI  and  LIMBERGER  .  Centralbl.  f.  in- 

nere Med.,  1897,  xviii.  4. 

24.  DAVID Zeitsch.    f.    Heilk.,     1896, 

xvii.  439. 

25.  SCHONDORFF    .   .  A.  G.  P.,  1896,  Ixiii.  423. 

26.  IRSAI,  VAS,  and  GARA  .  D.  M.  W.,  1896,  xxii. 

27.  MAGNUS-LEVY.  .  S.  Jb.,ccliii.  19;  D.  M.W., 

1896,  xxii. 

28.  SCHONDORFF    .  .  A.  G.  P.,  1897,  Ixvii.  395. 

29.  BETTMANN     .  .   .  B.  K.  W.,  1897,  xxxiv. 

30.  JAMES B.  M.  J.,  Aug.  4,  1894. 

31.  POYES B.  K.  W.,  1900,  xxxvii.300. 

32.  BERGMANN    .  .  .  S.  Jb.,  1897,  ccliii.  18. 

33.  GOULD B.  M.  J.,  1898,  ii. 

34.  DOBROWSKY  .   .   .  Ann.  d.  Kinderheilk.,  1896, 

xxi. 

35.  DIABALLA   and    ILLYES  .  A.  E.  P.  P.,  1897, 

xxxix.  273. 

36.  LEPINE Lyon  M.,  1896,  Ixxxii. 

37.  MURRAY Annals   of   Surgery,    1900, 

xxxi.  696. 

SUPRARENAL   CAPSULES. 

1.  OLIVER  and  SCHAFER  .  J.  P.,  1895,  xviii. 

2.  SZVMONOWICZ  and  CYBULSKI  .  Cb.  P.,  ix. 

3.  LANGLOIS  .   .   .   .  C.  R.  S.  B.,  1896,  10  s.,  iii. 

4.  ABEL Johns  Hopkins Hosp.  Bull., 

July,  1897. 

5.  ABEL A.  J.  P.,  1899,  ii..  No.  3; 

Bericht.  d.  Deutsch. 
Chem.  Gesellsch.,  1903, 
xxxvi,  1839.  Journ.  Biol. 
Chem.  1905  i. 

6.  DREYER A.  J.  P.,  1899,  ii.  203. 

7.  PETTIT C.  R.  S.  B.,  1896, 10  s.,  iii. 

322. 

8.  CORONA  and  MORONI  .  Rif.  M.,  1898,  xiv.  433. 

9.  BOINET C.  R.  S.  B.,  1896, 10  s.,  iii. 

364- 

10.  ABELOUS     .   .   .  .  C.  R.  S.  B.,  1895,  10  s.,  ii. 

11.  LANGLOIS  and  CHARRIN  .  C.  R.  S.  B.,  1896, 

10  s.,  iii.  14. 

12.  CAUSSADE  .   .   .  .  C.  R.  S.  B.,  1896,  iii.  67. 

13.  OTT  and  HARRIS  .  T.  G.,  1903,  xxvii.  378. 

14.  LANGLOIS  .  .   .   .  A.  de  P.,  1898,  x.  124. 

15.  CARNOT  and  JOSERAND  .  C.  R.  S.  B.,  1902, 

liv.  1472. 

16.  VINCENT     .  .   .  .  J.  P.,  1892,  xxii.  in. 

17.  ABEL Z.  P.  C.,  1899,  xxviii.  318. 

18.  ABBOTT J.  M.  R.,  1903,  iv.  329. 

19.  CROFTAN    ....  Am.  Med.,  1902,  iii.  113. 

20.  HURTER   and    RICHARDS  .  M.    News,    1902, 

Ixxx.  201. 

21.  PATON        .  .  .  .  J.  P.,  xxix.  286. 

22.  CYOS A.  G.  P.,  1899,  Ixxiv.  97. 

23.  GEARHEART  .  .  .  A.  E.  P.  P.,  1900,  xliv.  161. 

24.  MELTZER    ....  Am.  Med.,  1903,  v.  216. 

25.  JOSUE C.  R.  S.  B.,  1903,  Iv.  30. 

26.  GOTTLIEB  .   .   .   .  A.  E.  P.  P.,  1899,  xliii. 

27.  KONIGSTEIN  .   .   .  Wien.  Med.   Presse,  1897, 

xxxviii.  857. 

28.  DE  SCHWEINITZ  .  T.  G.,  1902.  xxvi.  433- 


556 


GENERAL  REMEDIES. 


29.  KYLE T.  G.,  1902.  xxvi.  438. 

30.  CARNOT  and  JOSERAND  .  C.  R.  S.  B..  1903,  liv. 

1346. 

31.  FLOERSHEIM    .  .  M.  News,  1902,  Ixxx.  17. 

32.  SCHAFER     .   .   .   .  B.  M.  J.,  1901,  i.  1009. 

33.  EHRMANN  ....  A.  E.  I'.,  P.,  1905,  liii.  97. 

34.  KCI.BS A.  E.  P.  P.,  1905,  liii.  140. 

35-  ERB A.  E.  P.  P.,  liii.  173. 

36.  PATON J.  P.,  1904,  xxxi.  92. 

37.  DRUMMOND   .   .   .  J.  P.,  xxxi.  89. 

PITUITARY  BODY. 

1.  OLIVER  and  SCHAFER  .  J.  P.,  1895,  xviii. 

2.  CYON A.  G.  P.,  1898,  Ixxiii. 

3.  HOWELL J.  Ex.  M.,  1898. 

4.  SCHIFF 2.    K.    M.,    1897,    xxxii., 

Suppl.,  284. 

5.  MAIRET  and  Bosc  .  A.  de  P.,  1896,  100. 

SPLEEN, 
i.  CLARK Ed.  M.  J..  1898,  iii.  152. 

THYMUS  GLAND, 
i.  MACKENZIE  .   .   .  A.  J.  M.  S.,  1897,  cxiii. 

ANTITOXINS. 

1.  VON  RUCK  ....  Journal    of    Tuberculosis, 

1903,  v.  165. 

2.  MUSSER U.  M.  M.,  March,  1900. 

3.  GOODRICH  ....  Annals  of    Surgery,    Dec. 

1897. 


REFERENCES.— Continued. 

TSUZUKI A.  I.  P.  T.,  1901,  viii.  19. 


5.  BEHRING    .  .  .  .  D.  M.  W.,  1900,  xxvi.  29. 

6.  LOEB Ann.  Otol.  Rhin.  Laryng., 

June,  1905. 

SNAKE-POISON. 

1.  PHISALIX  and  EERTRAND  .  C.  R.  A.  S.,  1894. 

cxviii.    356 ;    1895,    cxxi, 

754- 

2.  CALMETTE     .   .   .  C.  R.  S.  B.,  1894,  10  s.,  i. 

in  ;  Ann.  de  1'Inst.  Pas- 
teur, 1895,  ix.  225. 

3.  MITCHELL  and  REICHERT  .  Publications  of 

the  Smithsonian  Institute, 
1886. 

4.  MCFARLAND  .   .   .  J.  A.  M.  A.,  Dec.  14,  1901. 

5.  NOGUCHI     .   .   .   .  U.  P.  M.  B.,  1904,  xvii.  154. 

6.  FRASER B.  M.  J.,  1896,  i.  957. 

LECITHIN. 

1.  WOOD,  JR U.  P.  M.  B.,  1902. 

2.  DANILEWSKY    .   .  C.  R.  S.  B.,  1897,  iv. ;  C.  R. 

A.   S.,   1896,  cxxiii. ;    A. 
G.  P.,  1895,  Ixi. 

3.  SERONO A.  I.  B.,  1897,  xxvii. 

4.  CLAUDE  and  ZAKY  .  R.  T.,  1901,  Ixviii. 

5.  GILBERT  and  FOURNIER  .  C.  R.  S.  B.,  1901, 

liii. 

6.  LANCEREAUX  and  PAULESCO  .  B.  A.  M.,  1901, 

xlv. 


FAMILY  IV.— ANTIPERIODICS. 


CINCHONA.     U.S. 

THE  U.  S.  Pharmacopoeia  formerly  recognized  three  varieties  of 
Cinchona, — namely,  Cinchona  Flava  or  Yellow  Cinchona,  Cinchona  Pal- 
lida  or  Pale  Cinchona,  and  Cinchona  Rubra  or  Red  Cinchona.  At  present, 
under  the  general  heading  of  Cinchona,  it  recognizes  the  bark  of  all 
species  of  the  genus  yielding  when  assayed  by  the  official  process  not 
less  than  five  per  cent,  of  the  alkaloids  and  two  and  five-tenths  per 
cent,  of  quinine. 

The  genus  Cinchona  contains  numerous  species,  yielding  quinine 
and  its  congeneric  alkaloids,  indigenous  to  the  western  and  northern 
portions  of  South  America,  where  they  grow  upon  the  slopes  of  the 
Andes,  at  an  altitude  of  from  five  to  ten  thousand  feet.  Formerly  the 
only  cinchona  known  to  commerce  was  collected  by  the  cascarilleros,  or 
woodmen,  and  exported  in  large  bundles  or  bales,  usually  covered  by 
raw  hide  (jseroons).  The  natural  commerce,  however,  in  the  quinine 
barks  has  almost  disappeared  under  the  conjoint  influence  of  excessive 
production  by  cultivation  and  reckless  destruction  of  the  original  for- 
ests. At  present  the  world's  market  is  supplied  with  the  cinchona 
barks  chiefly  from  plantations  in  the  Himalaya  Mountains,  in  Ceylon, 
and  in  Java.  For  a  full  account  of  this  most  important  industry  the 
reader  is  referred  to  the  very  able  article  by  H.  H.  Rusby  in  the  United 
States  Dispensatory. 

CHEMICAL  CONSTITUTION. — Besides  tannic,  kinic,  and  kinovic  acids, 
and  other  important  substances,  the  cinchona  barks  contain  quinine 
and  quinidine,  cinchonine  and  cinchonidine.  Out  of  these  alkaloids 
quinicine  and  cinchonicine  are  readily  formed  artificially,  but,  so  far 
as  is  known,  they  do  not  exist  in  nature.  There  are  therefore  two 
isomeric  alkaloidal  groups  :  quinine,  quinidine,  quinicine  ;  cinchonine, 
cinchonidine,  cinchonicine.* 

The  official  preparations  of  Cinchona  are  the  fluid  extract  (FLUID- 
EXTRACTUM  CINCHONA,  U.  S. ),  dose,  thirty  minims  (2  C.c. ),  and  the 
compound  tincture  (TINCTURA  CINCHONA  COMPOSITA,  U.  S. ),  Hux- 
Aant's  tincture,  dose,  one  to  three  fluidrachms  (4-7  C.c.). 

*  Out  of  the  quinine  alkaloidal  groups  have  been  formed  by  chemists  various  isomeric 
alkaloids.  For  physiological  study  of  these,  see  Archiv  Physiol.  Norm,  et  Path.,  1893,  v- 

557 


558  GENERAL  REMEDIES. 


QUININA— QUININE.     U.  S. 

This  alkaloid  was  first  distinctly  separated  from  the  other  ingredi- 
ents of  fhe  bark  by  Pelletier  and  Caventou  in  1820.  When  quinine  is 
precipitated  by  an  alkali  from  a  solution  of  its  salt,  it  usually  falls  as  a 
hydrate,  which  may  be  crystalline.  By  sufficient  heat  the  hydrate  is 
melted  and  the  water  is  driven  off.  On  cooling,  the  alkaloid,  now  free 
from  water,  forms  a  white,  opaque,  crystalline  mass. 

The  neutral,  official  quinine  sulphate  (  QUININE  SULPHAS,  U.  S. )  oc- 
curs in  light  silky  crystals,  soluble  in  seven  hundred  and  forty  parts  of 
cold  or  in  thirty  of  boiling  water,  readily  soluble  in  alcohol,  very  freely 
so  in  acidulated  solutions,  nearly  insoluble  in  ether.  Therefore,  when  it 
is  administered  either  by  the  subcellular  tissue  or  by  the  rectum  the 
alkaloid  should  be  given  in  the  form  of  the  bisulphate  and  in  distinctly 
acidulated  water. 

The  authority  mentioned  found  that  one  thousand  parts  of  blood  which  was 
defibrinated  and  deprived  of  its  gases  at  a  temperature  of  36°  C.  dissolved  in  an 
hour  only  0.398  part  of  pure  quinine.  Water  saturated  with  carbonic  acid  gas  dis- 
solves the  quinine  sulphate  pretty  freely  ;  and  Kerner  also  experimentally  deter- 
mined that  when  a  neutral  solution  of  a  salt  of  quinine  is  added  to  a  very  dilute  so- 
lution of  sodium  carbonate  no  precipitate  occurs.  It  would  appear,  then,  that 
the  quinine  is  held  in  solution  in  the  blood  by  reason  of  the  loosely  combined  car- 
bonic acid  gas  in  that  fluid. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Quinine  is  distinctly  irri- 
tant to  the  mucous  membranes,  but  has  little  or  no  influence  upon  the 
sound  skin.  As  stated  as  long  ago  as  1765  by  Pringle,  the  cinchona 
bark  itself  is  distinctly  antiseptic.*  More  recent  researches  have  demon- 
strated that  quinine  is  actively  germicidal,  and  that  in  the  proportion  of 
one  part  to  three  hundred  it  will  preserve  for  a  long  time  flesh,  meal,  milk, 
butter,  urine,  albumin,  etc.,  and  will  check  very  markedly  the  alcoholic 
fermentation  in  honey  or  in  syrup. 

According  to  the  experiments  of  Binz,  the  larger  infusoria,  such  as  Paramecia 
and  Colpoda,  are  killed  by  a  solution  of  quinine  of  the  strength  of  i  in  800  immedi- 
ately, of  i  in  1000  after  some  minutes,  of  i  in  20,000  after  some  hours.  Upon 
the  ordinary  mould  Penicillium,  upon  Vibrios  and  Bacteria,  as  well  as  upon  the 
higher  infusoria,  quinine  acts  with  a  similar  fatality.  In  the  case  of  the  Vibrios 
and  Bacteria  a  decidedly  stronger  solution  than  the  one  mentioned  is  required  to 
quiet  movement.  Bochefontaine  found  that  a  solution  of  one  per  cent,  was  needed 
for  a  vigorous  rapid  action,  and  that  some  active  granules  could  even  be  found  in 
it  after  three  days. 

The  fact  that  fungi  will  appear  after  a  time  in  an  ordinary  solution  of 
quinine  sulphate  demonstrates  that  at  least  upon  some  of  the  lower  organ- 

*  Mayer,  Pavisi,  Hallier  (Das  Cholera-Contagium,  Leipsic,  1867),  Herbst,  Polli,  and 
especially  Binz  (  Virchow's  Archiv,  1869,  xlvi.  68;  and  Untersuchungen  uber  das  Wesen 
der  Chininwirkung ,  20). 


ANTIPERIODICS.  559 

isms  it  has  some,  but  comparatively  little,  influence,  although  on  others  it 
acts  with  much  power. 

Absorption  and  Elimination. — Owing  to  its  insolubility  in  simple 
water  or  alkaline  solutions,  quinine  can  enter  the  body  with  rapidity  only 
under  circumstances  in  which  it  is  exposed  to  the  solvent  power  of  acids. 

Taken  into  the  stomach,  the  quinine  salt  is  dissolved  by  the  acid  gas- 
tric juice  ;  but  if  it  be  not  absorbed  at  once,  passing  into  the  intestines  it 
is  liable  to  be  precipitated  by  the  alkaline  juices  and  the  bile  .acids. 

That  a  considerable  portion  of  ingested  quinine  can  be  recovered  from  the 
faeces  has  been  proven  by  Kerner 1  and  other  chemists.  It  is  probable,  however,  that 
some  of  this  fecal  quinine  has  been  absorbed  and  subsequently  cast  out  by  the  liver 
as  a  very  insoluble  biliary  salt,  since  Albertoni  and  Ciotto  **  found  that  when  they 
injected  quinine  into  the  jugular  vein  it  failed  to  appear  in  the  bile,  although  when 
given  by  the  mouth  it  was  freely  eliminated  with  that  secretion. 

Quinine  is  eliminated  chiefly  through  the  kidneys,*  escaping  in  large 
part  unchanged,  but  probably  in  part  undergoing  alteration,  f 

According  to  Briquet,1  quinine  may  generally  be  found  in  the  urine  half  an  hour 
after  the  administration  of  a  large  dose.  Its  removal,  according  to  the  researches 
of  Binz,  goes  on  slowly,  for  it  is  stated  that  in  six  experiments  only  a  little  more 
than  two-thirds  of  the  ingested  quantity  was  excreted  in  the  first  forty-eight  hours. 
Further,  De  Renzi,3  Yvon,  and  Dietl 4  have  found  it  in  the  urine  six  ©r  seven  days 
after  the  ingestion  of  the  last  dose.  It  is  probable  that  some  of  the  quinine  is  elimi- 
nated through  other  channels  than  the  kidneys,  since  Binz  had  found  it  in  the  saliva 
of  a  poisoned  dog,  and  Landerer 5  states  that  he  has  detected  it  in  the  urine,  sweat, 
tears,  milk  of  nursing  women,  and  in  the  serum  of  dropsical  effusions,  while  Al- 
bertoni and  De  Renzi  found  it  abundant  in  the  bile  when  it  had  been  taken  by  the 
mouth,  but  not  when  it  had  been  given  hypodermically.  Merkel 97  discovered  that 
in  the  dog  from  eighty-six  to  eighty-eight  per  cent,  of  the  quinine  escaped  unchanged 
from  the  kidneys,  the  remainder  being  converted  into  new  substances.  F.  K. 
Kleine 98  determined  that  29  per  cent,  escaped  through  the  urine  in  twenty-four  hours, 
the  elimination  being  at  its  height  in  about  six  hours  after  the  taking  of  the  drug. 

As  the  blood  is  alkaline,  a  priori  it  would  be  expected  that  the  qui- 
nine salt  would  be  precipitated  in  the  blood  ;  that  this  does  not  occur  is, 
according  to  the  researches  of  Kerner,  due  to  the  solvent  power  of  the 
carbonic  acid  in  normal  blood. 

*  See  analyses  of  Landerer  (Repertorium  fur  Pharmacie,  1836,  xxv.),  of  Dietl 
(  Wiener  Medizinische  Wochenschrift,  1852),  of  Briquet,  of  Binz,  and  of  De  Renzi  (Bull. 
Therap.,  xci.  45). 

t  G.  Kerner  (Pfliiger's  Archiv  fur  Physiologic,  1870)  asserts  that  the  quinine  as  ex- 
creted is  in  an  amorphous,  uncrystallizable  form.  He  also  has  discovered  in  the  urine 
of  persons  taking  quinine  a  peculiar  substance,  sometimes  amorphous,  sometimes  in 
acicular  prismatic  crystals,  free  from  bitter  taste,  possessing  the  quinine  inflorescence, 
which  he  believes  to  be  a  derivative  formed  in  the  body  from  the  ingested  alkaloid.  He 
has  not  been  able  to  get  this  substance  in  such  quantity  as  to  analyze  it  or  further  examine 
it,  but  has  produced  a  principle  (dihydroxyl-quinine)  which  he  believes  to  be  identical 
with  it  by  acting  on  quinine  with  the  potassium  permanganate.  An  elaborate  series 
of  experiments  have  shown  that  the  dihydroxyl-quinine  is  physiologically  inert.  This 
dihydroxyl-quinine  must  be  produced  in  small  amount,  if  at  all,  as  there  is  abundant 
evidence  that  quinine  is  largely  excreted  as  quinine  (see  Pharm.  Journ.  and  Trans., 
ix.  1255. 


56o  GENERAL  REMEDIES. 

The  question  as  to  the  rate  and  completeness  of  the  elimination  of 
quinine  is  one  of  great  practical  importance.  It  is  evident  that  it  is  both 
absorbed  and  eliminated  more  rapidly  when  it  is  given  in  solution  or  in 
the  form  of  the  acid  salt  than  when  taken  in  pill  6r  capsule.  Under 
favorable  circumstances,  with  the  dose  not  too  large,  it  is  probable  that 
absorption  is  practically  complete  within  two  hours  after  the  taking  of 
the  quinine  into  the  stomach,  so  that  the  maximum  effect  of  the  single 
dose  is  probably  reached  in  from  one  to  two  hours.  Thau  determined 
that  from  a  third  to  somewhat  less  than  half  of  the  ingested  quinine 
escapes  from  the  body  in  the  first  six  hours,  and  that  in  the  first  twelve 
hours  about  three-fourths  are  excreted.  Welitschkowski 6  found  an  elim- 
ination of  sixty-five  per  cent,  the  first  day  and  twenty-five  per  cent,  the 
second  day.  Prior  gives  the  second  day  as  the  usual  final  limit  of  elimina- 
tion. We  think  it  more  than  probable  that  after  a  few  doses  the  alkaloid  is 
practically  eliminated  in  forty -eight  hours,  but  that  when  it  has  been  given 
continuously,  or  when  kidney  disease  or  great  feebleness  of  circulation 
exists,  the  system  may  contain  a  notable  amount  of  the  quinine  for  a 
longer  period.  The  researches  of  Welitschkowski  are  in  accord  with 
those  of  Jiirgensen  and  Thau  in  showing  that  in  cardiac  and  renal  disease 
and  in  low  fevers  elimination  proceeds  very  slowly,  more  of  the  alkaloid 
being  thrown  off  in  the  second  than  in  the  first  six  hours  after  its  inges- 
tion. 

General  Effects. — The  first  symptoms  of  cinchonism,  as  produced  by 
full  therapeutic  doses  (ten  grains)  in  man,  are  usually  ringing  in  the 
ears,  slight  fulness  in  the  head,  and  perhaps  some  deafness.  With  the 
use  of  larger  doses  these  symptoms  are  intensified  :  the  deafness  is  very 
marked,  disturbed  vision  may  exist,  and  the  flushed  face,  with  a  sense 
of  distention  in  the  head,  may  point  towards  a  cerebral  congestion,  which 
is  in  some  cases  relieved  by  spontaneous  epistaxis.  In  decided  cin- 
chonism, giddiness  and  staggering  in  walking  are  very  common.  After 
toxic  doses,  severe  headache,  delirium,  stupor,  complete  deafness  and 
blindness,  dilated  pupils,  embarrassment  of  respiration,  great  weakness, 
convulsions,  paralysis,  and  finally  collapse  may  result,  either  comatose 
or  delirious.  Quinine  deafness  usually  passes  off  rapidly,  but  may  be 
permanent. 

In  the  lower  animals  large  doses  of  quinine  frequently  cause  violent  epilepti- 
form  convulsions.  Given  to  dogs  in  sufficient  quantity,  it  produces  restlessness, 
followed  by  muscular  tremblings,  which  have  been  compared  to  those  of  paralysis 
agitans,  loss  of  power  deepening  into  more  or  less  complete  paralysis,  great  dysp- 
noea, and  cerebral  symptoms,  such  as  anaesthesia,  blindness,  stupor,  or  violent  de- 
lirium, dilated  pupils,  coma,  and  convulsions.  When  the  drug  is  introduced  by  the 
stomach,  vomiting  generally  occurs,  and  at  times  diarrhoea  also.*  Death  has  been 


*See  F.  M.  Melier  (Mi-moires  de  V  Acadi-nrie,  1843,  xii.  722),  William  O.  Baldwin 
(Amer.  Journ.  Med.  Sci.,  April,  1847),  and  P.  Briquet  (  Traite  therap.  de  Quinquina, 
Paris,  1855). 


ANTIPERIODICS.  561 

shown  by  Heubach  to  be  produced,  at  least  in  the  lower  animals,  by  a  failure  of  the 
respiration.* 

A  close  physiological  study  of  quinine  can  best  be  made  by  investi- 
gating its  effects  upon  the  different  systems  of  organs  seriatim,  and  this 
shall  now  be  done. 

Cerebrum. — According  to  the  experiments  of  Briquet,  a  solution  of 
quinine  sulphate  injected  into  the  carotid  will  in  some  cases  produce 
meningitis.  In  doing  this,  it  is  evident  that  the  salt  acts  as  an  irri- 
tant to  the  membranes  of  the  brain  rather  than  as  a  nervous  stimulant : 
indeed,  experimental  evidence  proving  that  quinine  is  a  cerebral  stimu- 
lant seems  to  us  to  be  wanting.  The  chief  proof  that  the  alkaloid  does 
act  as  a  nervous  stimulant  lies  in  the  fact  that  persons  who  have  been 
taking  it  regularly  for  some  time  will  occasionally,  upon  the  sudden  with- 
drawal of  their  daily  dose,  manifestly  be  less  active  without  than  with  it. 
Briquet  may  be  right  in  his  belief  that  in  small  doses  it  acts  as  a  nervous 
stimulant,  but  the  proof  of  his  correctness  at  present  is  clinical  rather  than 
experimental.  When  given  in  toxic  doses  to  the  lower  animals,  probably 
all  of  the  cinchona  alkaloids  produce  epileptiform  attacks. 

J.  Jakoubowich 7  has  noticed  such  effect  with  quinine  in  dogs,  and  it  has  been  pro- 
duced with  cinchonidine  in  various  animals.  Chirone  and  Curci  found  that  in  the 
pigeon  this  action  of  cinchonidine  is  prevented  by  ablation  of  the  cerebral  hemi- 
spheres, but  Albertoni 8  objects  with  much  force  that  these  observers  gave  the  pigeon 
the  alkaloid  too  soon  after  the  ablation,  while  it  was  still  profoundly  affected  by  the 
shock  and  hemorrhage  of  the  operation.  Albertoni  found  that,  if  the  pigeon  is 
allowed  to  recover,  the  cinchonidine  is  capable  of  causing  convulsions ;  also  that 
in  dogs  with  the  motor  zone  of  the  cerebral  cortex  destroyed,  the  alkaloid  causes 
epileptiform  attacks,  and  that  therapeutic  doses  do  not  increase  the  excitability  of 
the  cerebral  cortex  in  the  dog. 

The  production  of  convulsions  in  the  lower  animals  is  of  great  inter- 
est in  connection  with  the  fact  noted  for  quinine  by  Brown-Sequard  and 
confirmed  by  Albertoni  as  regards  cinchonidine,  that  in  epileptics  the 
attacks  are  rendered  decidedly  more  frequent  by  the  cinchona  alkaloids. 
The  present  evidence  indicates  that  this  increase  is  not  due  to  an  influ- 
ence upon  the  cerebral  cortex,  but  can  hardly  be  considered  sufficient  to 
be  conclusive.  In  very  large  doses  quinine  without  doubt  abolishes  the 
functions  of  the  cerebrum. 

Louis  Dupuis 9  found  that  reflex  action  may  be  normal  in  poisoned  dogs  and 
rabbits,  although  there  is  complete  loss  of  sensibility  :  if  this  be  correct,  the  toxic 
dose  of  quinine  must  paralyze  the  perceptive  centres  in  the  cerebrum. 

*  The  present  is  perhaps  as  suitable  a  place  as  any  to  notice  certain  researches  upon 
the  relations  of  alkaloids  to  protoplasms.  The  relation  between  medicinal  substances  and 
the  tissues  upon  which  they  act  is  certainly  a  very  close  one,  and  very  probably  is  chem- 
ical in  its  nature.  Rossbach  (Pharm.  Untersuch.,\.  iii.)  found  that  various  alkaloids 
sensibly  modify  the  properties  of  albumin,  and  believes  that  they  form  a  chemical  com- 
pound with  it.  Under  the  influence  of  the  poison  the  albumin  coagulates  at  a  much 
lower  temperature,  and  is  deprived  of  its  affinity  for  ozone.  The  alkaloids  also  precipi- 
tate the  albumin  from  its  ozonized  solution. 

36 


562  GENERAL  REMEDIES. 

Special  Senses. — The  disorders  of  special  senses  caused  by  quinine 
are  due  to  an  action  upon  the  peripheral  sense  organs  ;  an  action  which 
is  probably  directly  exerted  upon  the  nerve-structure  involved,  and  is  not 
a  secondary  result  of  changes  in  the  circulation  of  the  organ,  although  it 
is  still  believed  by  many  authorities  that  the  drug  acts  directly  upon  the 
aural  and  retinal  circulation. 

In  regard  to  the  aural  action  of  quinine,  Roosa11  affirms  that  large  doses  of 
quinine  cause  congestion  of  the  blood-vessels  of  the  middle  ear,  and  in  our  own 
observation  in  persons  suffering  from  unilateral  chronic  inflammation  of  the  middle 
ear,  small  doses  of  quinine  will  produce  tinnitus  aurium  of  the  diseased  ear  without 
affecting  the  sound  ear.  Again,  the  fact,  long  since  pointed  out  by  Kirchner,10  that 
in  the  lower  animals  killed  with  quinine,  very  great  congestion  of  the  middle  internal 
ear  and  the  labyrinth,  with  bloody  exudation  and  in  some  cases  hemorrhage,  are 
present  after  death,  has  been  abundantly  confirmed  ;  but  Wittmaack,9*  as  the  result 
of  his  experimental  investigations,  believes  that  these  changes  are  not  caused  directly 
by  the  quinine,  but  are  the  result  of  the  long  drawn  out  suffocation  which  precedes 
death.  Wittmaack  further  finds  that  the  ganglionic  cells  of  the  cochlear  ganglion  are 
very  distinctly  altered  by  the  poison,  the  anatomical  changes  being  demonstrable 
four  hours  after  the  taking  of  the  fatal  dose.  He  was  also  able  to  detect  alterations 
in  the  protoplasm  in  these  cells,  as  the  result  of  chronic  poisoning  with  quinine. 

Analogy  would  indicate  that  as  in  the  retina  so  also  in  the  peripheral  aural 
apparatus,  the  first  effect  of  quinine  upon  the  circulation  is  a  spasm  of  the  vessels, 
but  at  present  there  is  no  proof  of  this.  The  evidence  still  indicates  (not  demon- 
strates) that  quinine  does  cause  congestion  of  the  peripheral  nerve  aural  apparatus, 
but  whether  this  is  or  is  not  preceded  by  a  period  of  ischaemia,  and  whether  it 
is  primary  or  secondary  to  the  action  of  the  drug  upon  the  nerve-endings  them- 
selves, is  undetermined. 

More  or  less  complete  amblyopia  may  be  produced  by  quinine  and  end 
in  permanent  loss  of  sight.*  In  most  of  the  numerous  recorded  cases 
the  amount  of  quinine  ingested  has  been  very  large,  but  we  have  seen  in 
one  individual  twelve  grains  of  quinine  repeatedly  produce  temporary 
blindness.  The  disturbance  of  vision  may  come  on  abruptly  or  gradually. 
When  fully  developed  it  is  usually  accompanied  by  dilatation  of  the  pupils, 
absence  of  the  light  reflex,  and  imperfect  response  to  accommodative 
effort.  There  have  also  been  noted  nystagmus,  divergent  strabismus, 
anaesthesia  of  the  conjunctiva,  and  increased  ocular  tension. 

When  the  blindness  is  not  complete  there  is  usually  pronounced  contraction 
of  the  field,  or,  in  rare  cases,  scotomata.  The  disturbance  of  vision  may  subside 
with  the  specific  action  of  the  drug,  but  it  may  persist  for  days  or  months,  or  even 
permanently.  The  color-sense  is  probably  first  affected  ;  certainly  it  usually  does 
not  recover  itself  until  after  the  return  of  central  vision.  The  ophthalmoscopic  ex- 
amination commonly,  but  not  always,  has  revealed  pallor  of  the  optic  disks,  with 
excessive  lessening  in  the  size  of  the  retinal  vessels ;  indeed,  in  some  cases  there 
has  been  complete  obliteration  of  the  vessels  of  the  optic  nerve.  Graefe  has,  how- 

*  According  to  Rogers  (Journ.  Amer.  Med.  Assoc.,  1889),  one  or  two  hours  after  the 
ingestion  of  twenty  grains  of  cinchonine  sulphate  there  can  usually  be  observed  paresis 
of  accommodation,  which  may  increase  until  it  becomes  almost  complete.  It  seems 
hardly  possible  that  this  phenomenon,  if  an  habitual  one,  could  have  been  overlooked  by 
other  observers. 


ANTIPERIODICS.  563 

ever,  noted  quinine  blindness  with  normal  ophthalmoscopic  appearances,  whilst 
Dickinson  describes  congestion  of  the  retina  and  choroid,  and  Gruening  M  and 
Mellinger87  record  hyperaemia  of  the  disk.  The  pathogenesis  of  quinine  amaurosis 
in  dogs  has  been  studied  by  Brunner,  De  Schweinitz,88  Burabaschew,89  De  Bono,90 
Holden,91  and  Druault.9*  The  visual  disturbances  are  due  to  a  degeneration  of 
the  ganglion  cells  of  the  retina  and  the  optic  nerves,  which,  with  the  tracts,  finally 
become  completely  atrophic.  The  primary  lesion  is  in  the  nuclei  of  the  cells,  where 
it  may  be  demonstrated  ten  hours  after  the  injection  of  the  drug.  The  breaking 
down  of  the  least  resisting  elements  of  the  inner  retinal  layers — the  ganglion  cells 
and  nerve-fibres — is  commonly  believed  to  be  caused  partly  by  a  lessened  blood- 
supply  due  to  spasm  of  the  retinal  vessels  and  partly  by  a  direct  action  of  the  drug 
on  the  protoplasm  of  the  cells.  An  ascending  atrophy  of  the  optic  nerve  follows. 
The  spasm  of  the  retinal  vessels  has  been  attributed  to  an  action  of  the  drug  on 
the  vaso-motor  centres,  which  is  unlikely,  and  to  its  influence  on  the  vessel  walls  or 
on  the  peri  vascular  vaso-motor  plexus.  De  Bono's  theory,  that  paralysis  of  the 
neuro-epithelium  of  the  retina  causes  the  amaurosis,  has  not  been  confirmed.* 

Spinal  Nerves  and  Centres. — Schlockow  was  the  first  to  notice  a 
stage  of  increased  reflex  activity  produced  in  the  frog  by  quinine  ;  its 
existence  was  subsequently  denied  by  A.  Eulenburg,12  but  has  been  reaf- 
firmed by  H.  Heubach13  and  by  David  Cerna,14  who  agree  in  finding  that 
it  occurs  only  after  very  minute  doses.  In  his  investigations  made  in  the 
laboratory  of  the  University  of  Pennsylvania,  Cerna  found  that  this  stage 
of  excitement  is  probably  caused  by  a  stimulant  influence  upon  the  pe- 
ripheral sensory  nerves,  as  it  did  not  occur  when  the  abdominal  aorta  was 
tied  previous  to  the  exhibition  of  the  alkaloid.  Two  facts,  first  pointed 
out  by  T.  A.  Chaperon,15  have  been  so  abundantly  substantiated  that  we 
must  accept  them  as  established.  They  are,  that  in  small  doses  quinine 
causes  in  the  frog  a  lessening  of  the  reflex  activity,  which  is  removed  by 
section  of  the  medulla,  and  in  large  doses  it  produces  a  permanent  palsy 
of  reflex  activity.  The  only  explanation  of  the  first  lessening  of  reflex 
activity  which  is  at  present  plausible  is  that  it  is  due  to  stimulation  of 
Setschenow's  centre. 

Sedgwick 16  combats  the  theory  just  spoken  of ;  he  believes  that  the  inhibition 
of  the  reflexes  is  such  as  occurs  when  a  sensitive  nerve  is  galvanized,  and  is  the 
result  of  a  stimulation  of  the  peripheral  afferent  cardiac  pneumogastric  nerve-end- 
ings by  the  quinine.  He  bases  his  theory  chiefly  on  the  fact  which  he  has  discov- 
ered, that  atropine  prevents  the  primary  inhibition  of  reflexes  by  quinine.  This  is, 
however,  readily  explainable  without  the  adoption  of  the  theory  of  Sedgwick,  and 
the  results  which  he  obtained  after  division  of  the  pneumogastrics  are  scarcely 
in  accord  with  his  theory. 

The  cause  of  the  permanent  influence  upon  reflex  activity  has  not  yet 
been  accurately  determined,  but  there  is  reason  for  supposing  that  pe- 
ripheral sensory  nerve-endings  are  first  paralyzed. 

*  For  discussion  of  the  subject,  with  resume  of  the  literature,  see  Toxic  Amblyopias, 
George  E.  de  Schweinitz,  1896,  and  Norris  and  Oliver's  Diseases  of  the  Eye,  1900,  iv.  832 ; 
for  case  of  blindness  lasting  twenty-one  days,  see  Brit.  Med.  Journ.,  1886,  i.  823. 


564  GENERAL  REMEDIES. 

Chaperon  and  Wild  found  that  the  motor  nerve-trunks  are  unaffected,  but  this 
does  not  prove  that  the  spinal  centres  are  paralyzed,  especially  as  Wild's  experi- 
ments seem  to  show  that  the  nerve-endings  in  the  muscles  are  attacked.  (See 
below. )  A.  Eulenburg  asserts  that  voluntary  movements  persist  after  reflex  actions, 
and  that  the  quininized  frog  will  turn  into  its  normal  position  when  laid  upon  its 
back,  although  ordinary  reflex  actions  are  completely  abolished.  This,  if  correct, 
certainly  shows  that  it  is  either  the  sensory  nerves  or  the  receptive  centres  of  the  cord 
whose  paralysis  by  quinine  puts  an  end  to  ordinary  reflex  movements.  So  that, 
accepting  the  various  results  reached  by  experimenters,  it  is  probable  that  in  frogs 
quinine  first  excites  and  then  paralyzes  the  peripheral  sensitive  nervous  system. 

Muscles. — According  to  the  experiments  of  H.  Robert,17  very  large 
doses  of  cinchonine,  and  probably  therefore  of  quinine,  lessen  the  excita- 
bility of  the  muscles.  This  is  confirmed  by  the  experiments  of  R.  B. 
Wild,18  who  finds  that  solution  of  quinine  i  to  1000  brought  in  contact 
with  the  isolated  muscles  of  the  frog  diminishes  the  irritability  of  the 
muscle  and  alters  to  some  extent  its  relations  with  stimulation.  The 
peripheral  nerve-endings  appear  to  be  more  sensitive  than  is  the  muscle, 
for  when  a  solution  of  i  to  4000  was  employed,  galvanization  of  the 
nerve  failed  to  elicit  a  response,  although  the  muscle  contracted  when 
the  current  was  applied  to  it  directly. 

Abdominal  Organs. — Upon  the  stomach  and  intestines  quinine  acts 
very  much  as  does  a  simple  bitter.  In  moderate  doses  it  stimulates  diges- 
tion and  increases  the  appetite  ;  in  large  doses  it  not  infrequently  causes 
nausea  and  vomiting.  When  there  is  any  morbid  irritability  of  the 
mucous  membrane  of  the  stomach  or  bowels,  its  irritant  action  is  often 
very  marked,  and  its  continued  use  in  large  doses  has  been  known  to 
cause  gastritis. 

The  statement  of  Piorry,19  that  a  large  dose  of  quinine  would  produce 
a  distinct  immediate  lessening  of  the  size  of  the  spleen  in  cases  of  inter- 
mittent, appears  not  to  be  correct. 

Several  observers  *  have  stated  that  the  exposed  spleen  of  an  animal  can  be 
seen  to  contract  when  quinine  sulphate  is  injected  into  the  stomach,  veins,  or 
cellular  tissue  ;  but  other  investigators  f  have  failed  in  their  attempts  to  produce 
this  asserted  contraction.  The  experiment  necessitates  such  abnormal  exposure  of 
the  organ  that  only  a  very  pronounced  and  very  constant  diminution  could  estab- 
lish the  assertion  that  quinine  produces  contraction  of  the  spleen,  and  our  present 
knowledge  indicates  that  the  alkaloid  has  no  immediate  decided  influence  on  the 
size  of  the  organ. 

Organs  of  Circulation. — Briquet,  who  first  studied  closely  the  action 
of  quinine  upon  the  circulation,  found  that  in  large  doses  it  lowers  the 

*  Piorry  (Archives  Generates  de  Medecine ,  1847),  Pages  (Gazelle  Medicate,  1846), 
Kuchenmeister  (Archiv fur  Physiol.  Heilkunde,  x.),  Mosler  (Pathologic  der  Leukaemie, 
Berlin,  1872,  451),  and  Jerusalimsky  ( Centralblatt f.  Med.  Wissen.,  1876,  476).  The  latter 
observer  believes  the  contraction  to  be  caused  chiefly  by  an  action  on  the  peripheral 
splenic  nerves  and  muscles. 

t  Magendie  ( Gaz.  Med.,  1847),  and  especially  L.  T.  Bochefontaine  (Recherches  experi 
mentelles  a  la  Contractilitt  de  la  Rate,  Paris,  1873). 


ANTIPERIODICS.  565 

arterial  pressure  in  the  lower  animals.  The  experiments  have  been 
confirmed  by  various  observers,  notably  by  Schlock ow,20  A.  Eulenburg, 
and  Cerna.  It  has  been  abundantly  proved  that  the  alkaloid  thrown 
into  the  jugular  vein,  introduced  into  the  coronary  artery,  or  in  any 
way  brought  in  contact  with  the  heart,  lessens  the  force  and  frequency  of 
the  pulsations,  and  finally  produces  diastolic  arrest  ;  also  that  this  result 
is  not  influenced  by  separation  of  the  mammalian  heart  from  the  nerve- 
centres,  and  occurs  in  the  cut-out  frog's  heart.  In  man,  very  large  doses 
of  quinine  (thirty  to  sixty  grains)  lower  the  force  and  frequency  of  the 
pulse  ;  a  pulse-rate  of  40  has  been  noted,  and  in  reported  cases  of 
quinine-poisoning  the  pulse  has  been  imperceptible  at  the  wrist.  Under 
the  latter  circumstances  the  pulse-rate  may  be  increased,  but  the  cardiac 
force  is  reduced  to  a  minimum.  The  evidence  is  conclusive  that  both  in 
man  and  in  the  lower  animals  quinine  in  sufficient  amount  is  a  powerful 
depressant  to  the  heart-muscle  or  ganglia.  * 

Schroff 21  found  that  in  the  quininized  animal  neither  galvanization  of 
a  sensitive  nerve  nor  asphyxia  was  able  to  produce  vascular  contraction 
and  rise  of  blood-pressure,  and  Jerusalimsky22  asserts  that  in  frogs  dila- 
tation of  the  vessels  can  be  seen.f  Further,  Kobert,  experimenting 
with  the  excised  organs  of  the  warm-blooded  animals,  and  Wild,  ex- 
perimenting with  the  tortoise,  prepared  according  to  the  method  of  Ste- 
vens and  Donaldson,  have  found  that  very  weak  solutions  of  quinine 
sulphate  (i  part  to  5000)  cause  enormous  dilatation  of  the  vessels,  with 
consequent  increased  rapidity  of  passage  through  them  of  liquid  under 
pressure.  It  is  probable,  therefore,  that  the_/a//  of  the  arterial  pressure 
in  poisoning  by  quinine  is  in  part  the  result  of  an  action  upon  the  vessels.  J 

Both  Schroff  and  Jerusalimsky  noticed  that  the  fall  of  arterial  pressure 
produced  by  quinine  is  preceded  by  a  rise  of  the  pressure,  accompanied 
by  an  increase  of  the  cardiac  action.  This  observation  has  been  con- 
firmed by  G.  S6e  and  Bochefontaine  ; 2S  but  no  observer  seems  to  have 
shown  that  the  rise  of  pressure  is  more  than  a  temporary  phenomenon. 
See  and  Bochefontaine  affirm  that  the  increased  cardiac  action  continues 
some  time  after  the  pressure  begins  to  fall.  The  primary  rise  of  pressure 
may  be  the  result  of  a  stimulant  action  upon  the  vaso-motor  centres,  as 
Jerusalimsky  found  that  it  was  not  produced  after  division  of  the  cord. 
It  is  not  improbable  that  it  is  due  to  disturbances  of  respiration.  Jerusa- 
limsky attributes  the  increase  in  the  pulse-rate  to  paralysis  of  the  in- 

*  Pantellejeff  (Centralbl.f.  Med.  Wissensch.,  1880,  xvii.  529)  states  that  atropine  will 
cause  the  heart  arrested  by  quinine  to  recommence  its  action. 

t  M.  Chirone  believes  that  by  quinine  the  heart  is  arrested  in  active  dilatation.  The 
theory  is  very  improbable.  See  Rivista  Clinica  di  Bologna,  abstracted  in  Journ.  de 
Physiol.  Norm,  et  Patholog.,  1876,  844. 

Heubach,  in  a  series  of  experiments  on  the  influence  of  galvanization  of  a  sensitive 
nerve  upon  the  circulation  after  the  exhibition  of  quinine,  failed  to  detect  any  paralyzant 
action  of  the  drug,  although  in  some  of  his  experiments  the  reflex  activity  was  paralyzed. 

J  When,  in  Wild's  experiments,  the  action  of  quinine  was  maintained  for  a  length  of 
time,  the  dilatation  was  finally  followed  by  contraction,  which  contraction  was  in  all  prob- 
ability the  outcome  of  a  post-mortem  rigidity. 


566  GENERAL    REMEDIES. 

hibitory  apparatus, — a  view  which  is  supported  by  the  assertion  of  Cerna 
that  previous  section  of  the  pneumogastric  prevents  the  quickening  of  the 
pulse-rate. 

We  have  never  been  able  to  perceive  any  depressant  action  upon  the 
circulation  in  man  after  ordinary  therapeutic  doses  (three  to  five  grains) 
of  quinine,  and  we  believe  that  in  tonic  doses  quinine  produces  no  percep- 
tible sedation  of  the  circulation,  but  that  the  largest  antiperiodic  doses 
have  a  distinct  influence.* 

Blood. — According  to  Bonorn  and  Arvedi,  to  Magendie,  to  Mon- 
neret,  to  Melier,  and  to  Baldwin,  in  animals  killed  with  quinine  the  blood 
is  found  to  be  dark,  defibrinated,  fluid,  and  incapable  of  forming  a  clot. 
Briquet,  however,  denies  that  this  alteration  of  the  blood  is  constant,  or 
even  common,  in  quinine-poisoning,  as  he  found  it  in  only  four  out  of 
twenty-three  dogs  so  sacrificed  ;  and  he  believes  that  it  is  merely  an  ac- 
cident dependent  upon  the  method  of  death, — a  conclusion  which  has 
been  confirmed  by  H.  A.  Hare.  In  a  series  of  analyses  Briquet  found 
that  the  continued  use  of  quinine  augments  the  proportion  of  fibrin,  but 
lowers  that  of  the  red  corpuscles. 

In  1867  f  Binz  announced  the  fact  that  quinine  added  to  human  blood 
in  the  proportion  of  i  part  to  4000  immediately  checks  and  in  a  short 
time  arrests  the  amoeboid  movements  of  the  white  blood-cells.  Con- 
firmation of  this  has  been  furnished  by  Scharrenbroich,24  by  Kerner,25  by 
Geltowsky,26  and  by  Jerusalimsky.  The  minimum  effective  strength  of 
the  solution  has  been  found  to  vary  in  different  species  of  animals,  and 
even  in  different  individuals  of  the  same  species. 

It  is  a  matter  of  great  interest  to  determine  whether  quinine  acts  in  the  living 
organism  as  on  the  stage  of  the  microscope  ;  and,  to  settle  this  point,  Binz  "  has 
experimented  according  to  the  method  of  Cohnheim.  He  found  that  when  the 
mesentery  of  curarized  frogs  to  which  quinine  had  been  given  was  exposed  upon 
the  stage  of  the  microscope,  no  accumulation  of  white  blood-cells  in  the  small  ves- 
sels, or  passage  of  them  out  into  the  tissues,  occurred  upon  irritation  ;  or,  if  after  a 
time  these  phenomena  commenced,  they  were  at  once  checked  by  a  small  hypo- 
dermic injection  of  the  alkaloid.  When  the  inflammatory  process  had  already  com- 
menced in  a  "  Cohnheim  frog,"  an  injection  of  quinine  would  cause  the  out-wan- 
dering of  the  corpuscles  to  cease,  and  would  bring  about  a  gradual  clearing  of  the 
white  cells  from  the  choked-up  vessels.  Binz  further  took  two  young  cats  and, 
after  poisoning  one  of  them  with  quinine,  examined  their  blood.  In  the  blood  of  the 
unpoisoned  animal  the  white  cells  were  far  more  abundant  than  in  that  of  the 
poisoned  cat.  From  these  facts  Binz  deduced  the  conclusion  that  quinine  acts  de- 
structively in  the  system  upon  the  white  blood-corpuscles,  in  the  same  way  as  when 
they  are  out  of  the  body.  George  R.  Cutter28  and  H.  A.  Hare29  have  experimen- 
tally confirmed  the  effect  of  quinine  in  preventing  the  extrusion  of  white  blood- 

*  Some  studies  have  been  made  upon  the  action  of  the  drug  on  the  capillaries  of  the 
brain,  but  the  evidence  is  contradictory  and  insufficient.  Consult  Psychological  and 
Medico-Legal  Journal,  1875,  33;  also  Archives  of  Medicine,  i.  33. 

f  Archiv  fur  Microscop.  Anatomie,  1867,  iii.  Consult  also  Experimented  Unter- 
suchungen  uber  das  Wesen  der  Chininzvirkung,  Berlin,  1868 ;  Virchow's  Archiv,  1869, 
xlv.  137;  Berlin.  Klin.  Wochenschrift,  Nov.  1871. 


ANTIPERIODICS.  567 

cells  from  the  frog's  mesentery,  and  A.  Martin30  has  also  found  that  the  action 
of  the  drug  is  apparent  in  the  centre  of  parenchymatous  organs,  such  as  the  liver. 

The  correctness  of  the  original  observation  of  Binz,  that  quinine 
checks  the  out-wandering  of  the  white  blood-corpuscles  in  the  irritated 
mesentery  of  the  Cohnheim  frog,  must  be  considered  as  established,  but 
the  question  as  to  whether  the  failure  of  the  blood-corpuscles  to  escape 
from  the  irritated  vessels  is  due  to  the  arrest  of  their  amoeboid  movements 
by  the  quinine  is  not  so  easily  answered. 

Schwalbe  *  could  detect  no  difference  in  the  blood  of  a  cat  before  and  after 
poisoning  by  quinine  ;  and  the  experiments  of  Geltowsky  upon  frogs  and  guinea-pigs 
have  yielded  similar  results  :  in  all  his  animals  after  fatal  poisoning  by  the  alkaloid 
the  movements  of  the  white  corpuscles  were  very  active.  In  a  series  of  experi- 
ments H.  A.  Hare  found  that  the  vessels  in  the  cinchonized  frog  were  much  more 
contracted  and  had  their  walls  much  thicker  than  in  a  corresponding  frog  without 
quinine.  This  contraction  of  the  vessels  is  thought  by  Hare  to  be  the  result  of  a 
direct  action  exerted  by  the  drug  upon  the  muscular  coat  of  the  arterioles.  It  is 
certain  that  the  alkaloid  reduces  very  markedly  the  force  of  the  heart.  The  theory 
that  quinine  prevents  the  out-wandering  of  the  blood-corpuscles  by  lessening  the 
force  which  is  driving  the  corpuscles  and  at  the  same  time  increasing  the  resistance  of 
the  capillary  walls,  seems  to  us,  however,  scarcely  sufficient ;  moreover,  E.  Maurel 9S 
has  found  that  when  the  minimum  fatal  dose  of  quinine  is  given  to  the  rabbit  the 
leucocytes  take  on  the  rounded  form  which  is  characteristic  of  the  early  stage  of  the 
quinine  action  in  drawn  blood. 

The  present  evidence  makes  it  probable  that  the  toxic  dose  of  quinine 
has  a  demonstrable  action  upon  the  white  blood-corpuscles,  but  that 
therapeutic  doses  have  no  apparent  influence.  Upon  the  red  blood-cor- 
puscles quinine  exerts  a  distinct  influence  in  inhibiting  their  functional 
activity. 

When  blood  is  drawn  from  the  body  and  allowed  to  stand,  acid  is  developed  in 
it  (see  Zunst,52).  Binzsl  believes  that  this  development  of  acid  is  due  to  oxidation, 
and  by  an  elaborate  series  of  experiments  has  determined  that  quinine  (also  berberine 
sulphate  and  sodium  picrate  in  almost  as  great  degree)  inhibits  these  changes  very 
greatly.  These  experiments  are  in  accord  with  the  previous  ones  of  A.  Schulte  : ss 
the  facts  may,  therefore,  be  considered  proven. 

If  ozonized  oil  of  turpentine  be  dropped  into  an  alcoholic  solution  of  guaiac 
resin,  no  alteration  of  color  occurs ;  but  if  a  drop  of  blood  be  added,  the  blue 
appears  at  once, — i.e.,  the  blood  acts  as  a  carrier  of  ozone  from  the  turpentine  to 
the  resin.  Binz  has  found  that  quinine,  even  in  so  small  an  amount  as  i  part  in 
20,000,  has  a  perceptible  influence  in  preventing  this.  Similarly,  when  sodium  car- 
bonate is  thrown  into  a  dilute  watery  solution  of  indigo  sulphate  until  the  reaction 
is  decidedly  alkaline,  and  a  little  blood,  and  subsequently  ten  drops  of  ozonized 
turpentine,  are  added,  a  green  color  begins  at  once  to  develop,  and  in  a  little  while 
passes  into  the  clear  yellow  of  isatin.  In  this  case  also  the  blood  acts  as  a  carrier 
of  ozone ;  and  Binz  and  his  pupil,  Ransone",84  have  determined  that  quinine  also 
inhibits  this  action,  one  part  of  it  added  to  a  thousand  of  the  mixture  delaying  the 
change  of  color  for  an  hour.  In  these  experiments  Binz  used  a  large  number  of 
different  salts  of  quinine,  and  found  that  they  acted  identically.  He  further  demon- 

*  Quoted  by  Kerner  (Pfliiger's  Archiv,  i.  203). 


568  GENERAL  REMEDIES. 

strated  that  the  action  of  the  alkaloid  was  on  the  red  blood-corpuscles.  He  also 
found  that  in  young  cats  to  which  he  had  given  a  very  large  but  not  fatal  dose  of 
quinine  the  freshly  drawn  blood  affected  the  tincture  of  guaiac  much  less  than  it 
normally  should.  According  to  Maurer  one  per  cent,  of  a  quinine  salt  added  to 
fresh  blood  rapidly  destroys  the  red  disks. 

There  is  no  sufficient  evidence  to  show  that  the  action  of  quinine  upon 
the  blood  has  any  close  relation  to  its  general  action  on  the  organism. 
It  is  not  probable  that  the  antipyritic  influence  of  quinine  is  due  to 
depression  of  the  ozonizing  power  of  the  red  disks,  and  so  far  as  the 
white  blood-corpuscles  are  concerned  Binz  has  shown  that  quinine  affects 
all  animal  germinal  matter  ;  and  it  is  probable  that  the  protoplasm  of  the 
nervous  system,  being  more  specialized  than  that  of  the  white  corpuscles, 
is  more  susceptible  to  the  influence  of  the  alkaloid.  Moreover,  various 
drugs  attack  the  white  and  the  red  corpuscles  and  do  not  otherwise  act  as 
does  quinine. 

Binz  states  that  both  conine  and  camphor  act  more  forcibly  upon  the  white  cor- 
puscles out  of  the  body  than  does  quinine,  and  T.  Lauder  Brunton  and  Theo. 
Cash  M  have  found  that  morphine,  veratrine,  and  codeine  check  the  ozonizing  power 
of  the  blood,  while  digitalin,  picrotoxin,  and  caffeine  increase  it.  Each  of  these 
principles  has  its  own  peculiar  physiological  action,  differing  from  that  of  quinine 
and  the  other  alkaloids.  It  seems  absurd  to  attribute  such  diverse  physiological 
actions  to  the  one  common  property  of  the  group,  and  we  think  that  we  must  con- 
sider the  antozonizing  power  of  quinine  as  simply  one  of  its  functions,  and  not  as 
the  basis  of  its  relations  with  the  human  organism. 

Uterus. — In  1871  Monteverdi36  announced  that  quinine  is  an  active 
uterine  stimulant,  but  in  so  doing  brought  forward  nothing  that  was  novel. 

As  long  ago  as  1855  John  S.  Wilson "  called  attention  to  the  uterine  action  of 
quinine,  and  in  1860  reasserted  his  belief,  which  in  the  meanwhile  had  been  con- 
firmed by  J.  H.  Rich;  in  1858  Jos.  J.  West*8  wrote:  "Many  regard  the  use  of 
quinine  as  dangerous  and  even  criminal  in  any  disease  in  pregnant  women.  The 
belief  of  these  persons  is  that  this  substance  exercises  a  direct  influence  upon  the 
uterus,  causing  powerful  contractions  and  expulsion  of  the  foetus.  And  to  support 
this  notion  they  are  ready  to  bring  forward  innumerable  instances  of  abortion  after 
its  use, — of  cases  of  sudden  suppression  relieved  by  a  prompt  use  of  the  same 
remedy."  He  then  goes  on  to  say  that  these  abortions,  etc.,  were  due  to  the  in- 
termittent fever,  and  not  to  the  drug.  Surely  this  is  enough  to  show  that  the  oxy- 
tocic  action  of  quinine  was  believed  in  many  years  ago  by  our  Southern  practitioners. 

The  answer  to  the  question,  Has  quinine  ecbolic  qualities  ?  should  be 
made  out  in  three  different  directions.  First,  Is  there  any  evidence  of 
quinine  producing  abortion  in  healthy  women  or  in  females  of  the  lower 
animals  ?  Second,  How  strong  is  the  evidence  of  its  producing  abortion 
in  women  suffering  from  ague  ?  Third,  What  is  the  evidence  in  regard 
to  the  action  of  quinine  during  labor  ? 

In  regard  to  the  first  of  these  sub-questions,  the  only  affirmative  evidence  we 
have  met  with  is  in  the  experiments  of  Rancillia,89  who  saw  abortion  in  two  bitches 


ANTIPERIODICS.  569 

follow  the  administration  of  from  six  to  nine  grains  of  quinine  :  as  the  pups  in  one 
case  were  already  dead  before  the  administration  of  the  drug,  it  would  seem  that 
this  investigation  was  not  on  such  a  scale  as  to  be  at  all  conclusive.  Moreover,  we 
have  given  quinine  to  two  pregnant  cats,  in  one  case  in  sufficient  quantity  to  cause 
death,  without  disturbing  the  products  of  conception.  Furthermore,  we  have  met 
with  no  evidence  that  quinine  is  capable  of  inducing  abortion  in  healthy  pregnant 
women.  Sayre's40  case  is  certainly  no  proof  whatever  that  quinine  will  originate 
labor,  as  labor  had  commenced  under  the  influence  of  the  hot  and  cold  douche  and 
other  measures  employed  before  the  quinine  was  given.  Chiara,41of  Milan,  has  fur- 
nished very  strong  evidence  that  quinine  is  incapable  of  originating  uterine  contrac- 
tions in  healthy  pregnant  women.  In  his  public  service,  two  doses  of  a  gramme 
(15.34  grains)  each  were  given  without  effect  daily  for  two  successive  days  to  eight 
women,  all  in  the  eighth  month  of  pregnancy.  It  being  necessary  to  cause  abortion, 
one  gramme  was  given  daily  to  one  woman  for  seven  days,  and  to  another  for  three 
days,  without,  in  either  instance,  any  effect,  so  that  the  labor  had  to  be  brought  on 
in  the  usual  manner. 

On  the  whole,  we  believe  that  the  first  question  must  be  answered — 
quinine  is  incapable  of  producing  abortion  during  quiet  pregnancy. 

In  answer  to  the  second  sub-question,  some  evidence  has  already  been 
adduced  to  indicate  that  abortion  may  be  so  caused,  but  it  is  opposed  by 
much  stronger  facts. 

To  evidence  already  quoted  may  be  added  the  assertion  of  Walraven*2  that  he 
has  frequently  seen  the  exhibition  of  quinine  followed  by  abortion,  the  record  of  two 
cases  of  such  character  by  Burt,tt  and  no  doubt  the  affirmations  of  others  which  we 
have  not  seen.  Opposed  to  this,  however,  is  the  overwhelming  fact  that  the  great 
body  of  the  profession  have  for  centuries  been  giving  quinine  in  one  form  or  other  to 
pregnant  women  indiscriminately,  and  if  abortion  had  been  produced  it  must  have 
been  noted  long  ago.  Further,  direct  testimony  is  not  wanting.  Malaria  often  in- 
duces abortion,  and  Erwin,44  James  C.  Harris,16  and  A.  Russwurm  **  testify  from  per- 
sonal experience  that  quinine  will  arrest  abortion  from  such  cause.  J.  A.  Ashford,47 
Beauchamp,*  Rooker,*  J.  S.  May,*  and  A.  d'Arcourd  have  given  quinine  to  hun- 
dreds of  pregnant  women,  suffering  from  malaria,  in  large  doses  without  disturbing 
the  uterus. 

Other  testimony  might  be  adduced  ;  but  it  is  incredible,  in  the  face  of 
daily  experience,  that  even  the  largest  therapeutic  doses  of  quinine  are 
abortifacient  in  malarial  fevers  or  in  health. 

In  regard  to  the  third  sub-question,  f  it  seems  to  us  proved  that  qui- 
nine in  full  doses  (ten  to  twenty  grains)  is  a  stimulant  to  the  uterine  con- 
tractions during  labor.  The  pains  it  produces  so  exactly  simulate  the 
natural  ones  as  to  indicate  that  they  are  not  so  much  caused  by  a  specific 
action  of  the  drug  as  by  its  arousing  the  general  nervous  forces  of  the 
system.  Be  this  as  it  may,  most  of  the  leading  accoucheurs  of  Philadel- 
phia and  of  New  York  are  accustomed  to  rely  upon  quinine  in  cases  of 
uterine  inertia  from  exhaustion.  J 

*  See  American  Practitioner,  1870. 

t  For  details  of  the  evidence  the  reader  is  referred  to  the  third  edition.  Consult  also 
Practitioner,  xvii.,  xviii.,  xix. 

J  Certain  experiments  of  Wild  (Brit.  Med.  Journ.,  1887,  ii.)  suggest  that  the  quinine 
may  act  directly  upon  the  muscle-fibres  of  the  uterine  walls.  He  found  that  when  the 


57o  GENERAL  REMEDIES. 

Voluntary  Muscles. — C.  G.  Sauterson,48  in  a  series  of  experiments 
upon  both  cold-  and  warm-blooded  animals,  has  found  that  quinine  acts 
directly  upon  the  muscle-fibres,  increasing  the  susceptibility  and  power 
of  the  muscle,  but,  especially  in  the  cold-blooded  animal,  causing  it  to 
become  fatigued  more  readily  than  normal. 

Nutrition. — Ranke  was  the  first  to  notice  that  quinine  produces  a  great 
decrease  in  the  elimination  of  uric  acid,  and  thereby  provoked  many  in- 
vestigators to  the  making  of  researches. 

Ranke  was  confirmed  by  H.  V.  Bosse49  and  by  G.  Kerner.  The  latter  ob- 
server found  that,  when  about  nine  grains  of  quinine  were  taken  in  divided  doses 
during  the  course  of  the  day,  the  urea  was  decreased  not  quite  one-eighth,  the  uric 
acid  to  a  little  less  than  one-half,  the  kreatinine  was  slightly  increased,  and  the 
nitrogenous  material  decreased  about  one-ninth.  When  a  very  large  dose  (thirty- 
eight  grains)  was  taken  in  the  morning,  the  urea  and  the  kreatinine  were  each  de- 
creased about  one-fourth,  as  was  also  the  collective  nitrogenous  material  ;  the 
phosphoric  acid  was  lessened  about  one-fifth,  and  the  uric  acid  about  four-fifths. 
Zuntz  (quoted  by  G.  Strassburg50 )  found  that  twenty-five  grains  of  quinine  reduced 
his  elimination  of  urea  nearly  forty  per  cent.  A.  Schulte  also  found  that  1.8  grammes 
of  quinine  depressed  the  elimination  by  the  kidneys  thirty-nine  per  cent ;  yet  in  the 
experiments  of  Unruh  51  the  action  of  the  alkaloid  in  depressing  urea  elimination  was 
not  constant,  and  in  the  trials  of  H.  Oppenheim52  the  excretion  of  urea  was  actually 
increased.  Nevertheless,  the  experiments,  upon  the  dog,  of  Rabuteau83  and  of 
Hermann  von  Boeck54  bear  strong  evidence  to  the  fact  that  quinine  does  decrease 
the  elimination  of  urea. 

Considering  all  the  evidence,  and  especially  the  rather  recent  very 
elaborate  studies  of  Prior, K  we  are  warranted  in  believing  it  established 
that  quinine  powerfully  depresses  the  elimination  of  the  nitrogenous  excre- 
tory principles.  That  such  decrease  is  due  to  diminished  formation,  and 
not  to  lessened  elimination,  seems  proved  by  the  fact  that  in  Prior's 
experiments  there  was  no  increase  of  nitrogenous  excretion  beyond  the 
normal  following  the  omission  of  the  quinine.  It  seems,  therefore,  to  be 
established  that  quinine  has  a  direct  or  indirect  depressing  influence  upon 
the  tissue-changes  of  the  human  organism. 

Contrary  to  what  might  have  been  expected,  Strassburg,  in  an  elab- 
orate series  of  experiments,  found  that  quinine  had  no  decided  effect 
upon  the  elimination  of  carbonic  acid  either  in  healthy  or  in  fevered 
rabbits.  These  observations  of  Strassburg  are  opposed  by  those  of  Bock 
and  Bauer,56  who  found  that  in  cats  large  doses  of  the  alkaloid  cause  in 
the  first  stage  of  their  action  lessened  carbonic  acid  production,  but  that 
when  the  convulsions  appear  the  carbonic  acid  is  increased  as  the  result 
of  the  increased  muscular  activity.  R.  H.  Chittenden 57  found  that  fatal 
doses  of  quinine  given  to  fasting  rabbits  had  no  decided  effect  upon  car- 
solution  of  quinine  sulphate,  i  part  to  1000,  was  brought  in  contact  with  the  isolated 
oesophagus  of  the  frog,  the  oesophagus  first  shortened,  and  afterwards  lengthened  be- 
yond its  normal  limit,  the  change  probably  being,  as  believed  by  Wild,  due  to  stimulation 
first  of  the  weak  longitudinal  muscular  fibres,  and  later  of  the  more  internal  stronger  cir- 
cular fibres,  as  the  quinine  penetrated  the  coats.  The  muscle-fibres  of  the  oesophagus  are 
similar  to  those  of  the  uterus. 


ANTIPERIODICS.  571 

bonic  acid  production  until  just  before  death,  when  both  the  animal  tem- 
perature and  the  excretion  of  carbonic  acid  fell  distinctly.  On  the  other 
hand,  small  doses  of  quinine  seemed  to  cause  a  gradual  falling  off  in  the 
carbonic  acid  elimination.  Although  the  evidence  is  somewhat  contra- 
dictory, it  indicates  that  any  action  of  quinine  upon  carbonic  acid  elimi- 
nation must  be  very  feeble  and  uncertain. 

THERAPEUTICS. — At  present  our  estimate  of  the  value  of  quinine  in 
disease,  an'd  our  knowledge  of  its  therapeutic  use,  rest  solely  upon  clin- 
ical observation,  although  recent  discoveries  have  enabled  us  to  frame  a 
very  plausible  explanation  of  the  method  by  which  it  overcomes  malarial 
disease. 

On  account  of  its  power  of  arresting  or  preventing  putrefactive  fer- 
mentation by  killing  the  microscopic  entities  which  produce  such  changes, 
Binz  has  recommended  quinine  in  the  so-called  septic  diseases. 

The  chief  evidence  which  he  produces  is  in  some  ten  experiments  made  upon 
dogs  and  rabbits.  In  each  of  these  experiments  two  similar  animals  were  poisoned 
with  putrescent  liquids,  and  to  one  of  the  pair  quinine  was  freely  administered.  In 
two  cases  the  cinchonized  animal  recovered,  while  its  fellow  perished  ;  in  three  ex- 
periments neither  of  the  animals  died  ;  and  in  the  other  five  trials  the  cinchonized 
animal  lived  from  two  to  twenty-four  hours  longer  than  the  other.  These  experi- 
ments are  certainly  too  few  and  indecisive  to  prove  in  any  degree  Binz's  view. 
To  us  they  indicate  very  strongly  that  quinine  has  no  such  influence  over  the  dis- 
ease as  he  believes.  If  living  germs  in  the  blood  were  really  the  cause  of  the  septic 
symptoms,  and  if  quinine  killed  such  germs,  its  action  would  be  as  manifest  and  as 
unmistakable  as  it  is  in  intermittent  fever. 

The  results  of  Binz's  experiments  seem  to  us  to  agree  with  the  em- 
phatic teachings  of  clinical  experience  that  quinine  has  no  direct  specific 
influence  in  pycemic,  septic,  or  exanthematous  diseases. 

Before  the  introduction  of  modern  antipyretics  the  question  as  to 
the  power  of  quinine  of  lowering  bodily  temperature  was  extremely  im- 
portant, but  at  present  it  is  enough  to  know  that  as  an  antipyretic 
quinine  is  of  very  inferior  power. 

Unless  given  in  enormous  toxic  doses,  quinine  does  not  lower  bodily  tempera- 
ture in  health.  It  is  alleged,  however,  by  G.  Kerner  and  Jiirgensen  that  it  will 
largely  prevent  the  rise  of  the  bodily  temperature  which  normally  occurs  from  ex- 
ercise, and  it  is  asserted  by  various  clinicians  that  it  does  not  affect  the  tempera- 
ture in  fever.  C.  Liebermeister58  came  to  the  conclusion  that  quinine  given  in 
doses  of  from  twenty  to  forty-five  grains  in  one  hour  is,  in  typhoid  fever,  a  very 
active  and  certain  antipyretic,  a  conclusion  also  reached  by  the  Committee  of  the 
London  Clinical  Society.59 

Naunyn  and  Quincke60  found  that  sometimes  quinine  prevented  the  develop- 
ment of  fever  after  the  division  of  the  spinal  cord  in  animals,  but  in  other  cases 
failed  to  do  so.  Binz 61  has  achieved  similar  results  :  he  says  that  if  the  conditions 
of  the  fever  are  too  favorably  constituted  the  effect  of  the  quinine  fails  thoroughly. 

The  drift  of  our  present  clinical  evidence  seems  to  indicate  that  qui- 
nine exerts  in  febrile  disease  a  decided  antipyretic  action,  which  is  espe- 


572  GENERAL  REMEDIES. 

cially  manifested  during  those  stages  of  disease  in  which  the  natural  ten- 
dency is  towards  a  lowering  of  temperature.  In  exanthematous  diseases, 
etc. ,  after  the  use  of  the  cold  bath  twenty  grains  of  the  alkaloid  are  often 
efficacious  in  delaying  the  return  of  the  excessive  fever. 

As  a  simple  tonic,  quinine  is  largely  used,  especially  in  combination 
with  iron.  We  are  not  entirely  convinced  that  it  is  of  much  more  value 
in  simple  debility  than  is  quassia  or  other  simple  bitters  ;  but  if,  as  is  prob- 
able, it  be  true  that  quinine  lessens  to  a  very  great  extent  the  elimination 
of  nitrogen, — i.e. ,  the  consumption  of  tissue, — the  general  practice  is  well 
founded.  Hare,62  as  the  result  of  observations  made  upon  himself,  be- 
lieves that  quinine  has  a  distinct  action  in  increasing  the  formation  of  the 
red  blood-corpuscles.  If  this  be  correct,  it  must  have  especial  tonic  value. 

When  administered  in  very  large  doses,  quinine,  as  has  been  already 
shown,  acts  as  a  powerful  depressant,  and  as  such  it  has  been  used  by 
Briquet  and  other  French  physicians  in  rheumatism.  As  much  as  sixty 
or  seventy  grains  a  day  have  been  given,  and  it  is  beyond  dispute  that 
under  the  influence  of  these  heroic  doses  the  symptoms  of  inflammatory 
rheumatism  have  often  rapidly  abated  ;  but  the  method  has  found  little 
favor  out  of  France,  and  is  less  efficient  and  more  dangerous  than  other 
plans  of  treatment  now  in  vogue.  In  inflammatory  rheumatism,  after 
the  acute  symptoms  have  abated,  when  the  patient  shows  evident  signs 
of  weakness,  especially  if  there  be  profuse  sweating  during  sleep,  fifteen 
grains  of  quinine  daily  are  often  of  great  service. 

Conceiving  the  theory  that  choreic  movements  may  be  due  to  weak- 
ness of  the  spinal  inhibition,  H.  C.  Wood  some  years  ago  injected  quinine 
into  the  veins  of  choreic  dogs,  and  found  that  the  movements  were  at 
once  arrested  by  comparatively  small  doses  of  the  alkaloidal  salts.  This 
led  him  to  make  trial  of  the  remedy  in  the  chorea  of  childhood,  and  as 
the  result  of  much  experience  it  has  been  determined  that  the  drug  in 
some  cases  of  this  affection  is  of  great  value.  There  are  certain  cases  in 
which  enormous  doses  are  borne  without  the  production  of  cinchonism  : 
thus,  we  have  given  in  a  month  to  a  child  ten  years  old  one  thousand 
grains  of  the  quinine  sulphate  without  causing  tinnitus  aurium  or  other 
disagreeable  effect,  but  with  the  result  of  curing  a  chorea  which  had  resisted 
all  treatment  for  nearly  two  years.  In  our  experience  in  the  disease, 
when  there  is  no  tolerance  of  quinine  no  benefit  is  achieved  by  its  admin- 
istration, but  when  the  quinine  is  tolerated  in  large  dose  its  use  is  com- 
monly most  beneficial.  Led  by  the  results  obtained  in  chorea,  the  chief 
of  H.  C.  Wood's  clinic  at  the  University  Hospital,  Charles  S.  Potts,  con- 
ceived the  belief  that  incontinence  of  urine  might  in  many  cases  be  the 
result  of  failure  of  inhibition,  and  on  trial  found  that  very  large  doses  of 
quinine  often  put  an  end  to  this  most  annoying  symptom,  a  result  which 
we  can  confirm  from  our  own  experience. 

The  chief  value  of  quinine  is  as  an  antiperiodic.  There  is  at  present 
no  doubt  that  the  alkaloid  does  good  in  all  forms  of  malarial  fever  by 
directly  affecting  the  malarial  plasmodium  or  organism. 


ANTIPERIODICS.  573 

Quinine  in  its  relations  to  •malarial fever  may  be  considered,  first,  as  a 
prophylactic;  second,  as  a  curative  agent 

The  value  of  the  daily  use  of  quinine  to  persons  exposed  to  a  malarial 
atmosphere  has  now  been  thoroughly  tested  in  all  portions  of  the  world. 
In  North  and  South  America,  in  Europe,  in  Africa,  and  in  India  the  pro- 
phylactic powers  of  quinine  have  been  tried  on  the  largest  scale  in  connec- 
tion with  the  military  and  naval  services,  and  the  testimony  is  unanimous 
in  favor  of  the  drug. 

A  single  citation  will  serve  to  illustrate  this  fact.  J.  B.  Hamilton  M  reports  the 
case  of  a  battery  of  one  hundred  and  thirty-five  men,  quartered  at  Jubbulpore,  East 
Indies,  in  the  same  barracks  with  an  infantry  regiment.  Each  of  the  artillerists 
received  three  grains  of  quinine  every  other  day  :  to  the  infantry  none  was  given. 
The  result  was  that  while  three  hundred  out  of  the  five  hundred  men  of  the  regi- 
ment were  sick  at  one  time  with  malarial  disease,  at  no  period  was  more  than  four 
per  cent,  of  the  battery  affected. 

The  dose  of  quinine  as  a  prophylactic  may  be  considered  as  two 
grains  in  the  morning  and  three  in  the  evening. 

In  intermittent  fever,  when  there  is  sufficient  time,  it  may  be  well  to 
precede  the  quinine  by  a  mercurial  or  other  purge.  If  the  expected  par- 
oxysm be  so  near  that  there  is  not  sufficient  time  for  the  action  of  the 
purgative,  the  antiperiodic  should  be  administered  without  previous  prep- 
aration of  the  patient.  The  value  of  purgatives  in  obstinate  intermittents, 
as  an  adjuvant  to  quinine,  is  often  overlooked,  although  in  some  cases 
the  employment  of  purgatives,  and  of  such  diuretics  as  cream  of  tartar, 
seems  to  be  almost  essential  for  the  successful  use  of  the  antiperiodic. 

\&  penurious  fever i  or  malignant  malarial  poisoning \  no  time  should 
be  lost  after  the  first  paroxysm  in  getting  the  patient  cinchonized,  as  it 
may  be  uncertain  whether  the  attack  be  of  the  quotidian  or  of  the  tertian 
type.  At  least  sixty  grains  of  the  alkaloidal  salt  should  be  administered 
during  the  first  twenty-four  hours  ;  in  very  severe  types  of  the  disease 
even  larger  doses  than  these  are  necessary,  less  than  seventy-five  grains 
of  the  drug  sometimes  being  unable  to  suppress  the  disease. 

In  remittent  or  bilious  fever  it  may  often  be  advisable  to  give  purga- 
tives and  febrifuges  before  the  quinine.  As  soon  as  the  remission  has 
appeared,  the  exhibition  of  quinine  should  be  begun.  Local  inflamma- 
tions or  even  severe  cerebral  symptoms  occurring  during  a  remittent 
fever  are  no  centra-indications  to  the  use  of  the  specific.  When  gastritis 
exists,  other  channels  of  entrance  than  the  stomach  should  be  employed, 
on  account  of  the  local  irritant  action  of  quinine. 

When  the  symptoms  in  remittent  fever  are  severe  and  seemingly 
continuous,  it  may  be  not  only  proper  but  necessary  for  the  saving  of 
life  to  exhibit  quinine  freely  during  the  period  of  fever.  In  large  doses 
the  alkaloid  is  probably  antipyretic  as  well  as  antiperiodic,  and  we  do  not 
know  of  any  theoretic  or  clinical  objection  to  its  use  during  the  period  of 
fever. 


574  GENERAL  REMEDIES. 

In  malarial  intermittent  neuralgia,  as  in  all  other  forms  of  abnormal 
manifestations  of  malarial  disease,  quinine  is  efficient,  although  it  is 
usually  necessary  to  administer  it  in  large  doses  (thirty  to  forty  grains  at 
intervals). 

In  neuralgia  which,  although  not  dependent  upon  malaria,  assumes 
the  intermittent  type,  quinine  will  often  temporarily  set  aside  the  par- 
oxysmal attacks,  and  sometimes  effect  a  cure.  The  same  fact  may  be 
stated  in  broad  terms  as  true  of  all  non-malarial  intermittent  affections. 
In  the  great  majority  of  such  cases,  unfortunately,  the  action  of  the 
quinine  is  only  temporary,  and  any  controlling  power  is  soon  lost. 

Ordinarily  the  best  method  of  treating  a  case  of  intermittent  fever  is 
to  give  the  patient  a  full  mercurial  purge,  and  after  it  has  acted,  to  begin 
the  exhibition  of  the  drug  about  eight  hours  before  the  expected  par- 
oxysm, in  doses  of  five  grains  every  two  hours  until  from  fifteen  to 
twenty  grains  are  taken  ;  care  being  exercised  to  see  the  quinine  is  in 
such  form  as  to  secure  prompt  absorption.  In  cases  of  persistent  or 
chronic  intermittent  fever,  quinine  is  often  administered  in  moderate 
doses  day  after  day,  but  we  are  convinced  that  it  is  better  to  use  the 
remedy  in  large  doses  at  intervals  than  to  administer  it  continuously  in 
smaller  amounts.  In  this  climate  fifteen  grains  of  quinine  a  day  will 
usually  put  an  end  to  a  mild  intermittent,  but  the  paroxysm  will  be  very 
apt  to  recur,  even  if  six  grains  of  the  alkaloid  be  afterwards  given  daily 
for  some  weeks.  We  believe  it  is  better  to  administer  from  twenty  to 
twenty-five  grains  in  the  beginning,  sufficient  to  produce  very  pronounced 
cinchonism  and  to  arrest  the  disease  at  once.  The  full  physiological 
effect  of  the  drug  should  then  be  maintained  for  two  or  three  days,  and  no 
more  quinine  given  except  at  certain  intervals.  The  paroxysms  have  un- 
doubtedly a  great  tendency  to  return  on  the  seventh  day  after  their 
arrest,  and  every  seventh  day  for  some  weeks  full  cinchonism  should  be 
produced.  If  the  observation  of  Councilman,  that  large  doses  of  quinine 
entirely  destroy  the  malarial  organism,  be  correct,  the  practice  just 
spoken  of  has  a  foundation  in  scientific  as  well  as  in  empiric  observation. 

The  general  clinical  experience,  that  it  is  best  to  administer  quinine  so  that  the 
last  dose  will  be  given  about  two  hours  before  the  development  of  the  paroxysm,  is 
confirmed  by  the  various  experiments  which  have  been  made  upon  the  relation  of 
quinine  to  the  malarial  paroxysm.  (See  Golgi.95)  Monaco  and  Panichi 96  believe, 
as  proven  by  their  experiments,  that  the  results  obtained  are  not  due  to  the 
quinine  acting  more  powerfully  upon  the  young  forms  of  the  parasite  liberated  by 
the  processes  of  segmentation  just  before  the  febrile  outbreak,  but  are  due  to  the 
facts  that  quinine  remains  in  the  blood  during  the  fever,  and  that  the  old  parasites 
present  during  the  febrile  stage  are  more  susceptible  to  the  action  of  the  quinine 
than  are  the  younger  forms,  even  though  the  latter  be  not  protected  by  the  red 
blood-disks. 

Local  Use  of  Quinine. — The  effect  of  quinine  upon  the  lower  organ- 
isms has  suggested  its  local  use  in  various  disorders  supposed  to  depend 
upon  the  presence  of  such  entities.  Thus,  Henke,64  finding  some  pecu- 


ANTIPERIODICS. 


575 


liar  motile  cells  in  the  sputa  of  whooping-cough,  employed  inhalations  of 
quinine  with  asserted  good  results.  Henke  was  not,  however,  the  first 
to  suggest  either  this  fungoid  pathology  of  whooping-cough  or  the  use 
of  quinine.  Binz65  in  1870  asserted  that  quinine  had  a  specific  action  in 
whooping-cough,  provided  it  was  given  in  large  doses  in  solution,  so  as 
to  come  in  contact  with  the  mucous  membrane  in  its  passage  through  the 
pharynx;  and  in  1871  Letzerich66  announced  that  whooping-cough  was 
due  to  a  fungus  in  the  lung.  Dawson 6I  has  confirmed  the  value  of  the 
method  of  Binz  ;  but,  if  the  fungoid  theory  be — as  we  do  not  believe — 
true,  the  plan  of  Henke  must  certainly  be  the  better  one.  The  use  in 
hay-fever,  as  recommended  by  Helmholtz,  of  a  weak  tepid  solution  (one 
to  three  grains  to  one  fluidounce),  as  nearly  neutral  as  possible,  freely 
applied  to  the  nasal  mucous  membrane,  has  not  achieved  general  recog- 
nition, and  any  influence  which  the  alkaloid  has  in  either  whooping-cough 
or  hay-fever  probably  depends  on  its  direct  influence  upon  the  mucous 
membranes.  In  the  later  stages  of  gonorrhoea  the  topical  employment  of 
its  solution  (five  to  ten  grains  to  one  fluidounce)  may  be  serviceable.* 

Hypodermic  Use. — Owing  to  its  local  irritative  action,  and  the  in- 
solubility of  its  ordinary  salts,  quinine  does  not  lend  itself  well  to  hypo- 
dermic medication.  Great  local  disturbances,  abscesses,  ulcers,  and 
even  tetanus,69  have  followed  the  injection  of  the  sulphate  under  the 
skin.  Many  of  these  manifestations,  however,  were  undoubtedly  due  to 
lack  of  proper  asepsis.  Further,  in  severe  pernicious  malarial  affections, 
promptness  of  action  is  of  the  greatest  importance,  and  many  of  the 
German  practitioners  believe  that,  hypodermically  given,  quinine  acts 
much  more  favorably  as  an  antipyretic  than  when  given  by  the  mouth. 

Qidnine  sulphate  may  be  used  hypodermically — dissolved  in  a  solu- 
tion of  tartaric  acid.  Quinine  bisulphate  (QuiNiN^E  BISULPHAS,  U.  S. ) 
is  soluble  in  ten  parts  of  water,  and  is  preferable  to  the  ordinary  sulphate. 
One  gramme  (15  grains)  of  Quinine  hydrochlorate  (QuiNiN^E  HYDRO- 
CHLORIDUM,  U.  S. )  maybe  dissolved  in  i  c.c.  of  boiling  water,  and  does 
not  precipitate  until  the  temperature  reaches  100°  F.  For  hypodermic 
injection  it  is  better  to  dissolve  the  quinine  salt,  I  gramme  in  2  c.c.  of 
water,  and  give  in  two  injections  of  i  c.c.  each  if  ten  grains  are  required. 
According  to  Gagglio,  confirmed  by  Aufrecht,99  urethan  increases  the  sol- 
ubility of  quinine  so  that  the  following  formula  is  permanent  at  ordinary 
room  temperature:  Quinine  hydrochlorate,  0.5;  urethan,  0.25;  distilled 
water,  add  5  c.c.  Quinine  hydrobromate  (QuiNiN^E  HYDROBROMIDUM, 
U.  S. )  is  soluble  in  ten  per  cent,  of  water  containing  twenty-five  per  cent, 
of  alcohol,  and  its  solution  has  been  used  to  a  considerable  extent  hypo- 
dermically. 

QUININE   SALICYLAS.     U.    S. — Quinine    salicylate    is    often    very 

*  Walerian  Sokolow  affirms  that  the  local  application  of  quinine  to  wounds  has  a  very 
remarkable  effect  upon  the  granulation  tissue,  a  similar  effect  being  produced  by  the  ad- 
ministration of  the  drug  by  the  mouth.  (For  details,  see  Inaug.  Dissert.,  1891,  abstracted 
in  Schmidt's  Jahrb.,  1802.) 


576  GENERAL   REMEDIES. 

effective  in  subacute  muscular  and  neuritic  rheumatism,  or  in  the  sub- 
siding stages  of  acute  rheumatism.  It  may  be  given  in  doses  of  five 
grains  (o.  3  Gm. )  three  or  four  times  daily. 

ADMINISTRATION. — Ordinarily  quinine  is  used  in  the  form  of  the 
sulphate.  The  powder  should  be  given  in  capsules,  the  pill,  and  espe- 
cially the  sugar-coated  pill,  being  prone  to  become  hard  and  uncertain  in 
its  solubility  and  action.  If  immediate  action  is  required  the  solution 
may  be  used,  the  solubility  of  the  salt  being  guaranteed  by  the  addition 
of  one  drop  of  dilute  sulphuric  acid  to  every  grain  of  the  salt.  The 
quinine  hydrochlorate  is  as  efficacious  as  the  sulphate,  and  more 
soluble. 

Contra-indications. — On  account  of  its  irritant  properties,  quinine  must 
be  used  with  caution  when  there  is  irritability  or  inflammation  of  any  part 
of  the  gastro-intestinal  tract.  It  is  strongly  contra-indicated  by  inflam- 
mation of  the  middle  ear,  and  may  greatly  and  permanently  increase 
dulness  of  hearing.  The  statement  of  M.  Friedmann70  that  ergotin,  and 
that  of  W.  B.  Deweesn  that  chloral  greatly  lessens  the  tinnitus  aurium 
produced  by  quinine  and  salicylic  acid  need  confirmation.  Irritability  of 
the  bladder  or  other  portion  of  the  genito-urinary  tract  centra-indicates 
the  use  of  quinine  :  hence  it  is  often  badly  borne  by  old  men.  It  is  even 
asserted  that  it  will  in  some  persons  cause  hsematuria.* 

TOXICOLOGY. — The  general  symptoms  produced  by  toxic  doses  of 
quinine  have  been  sufficiently  discussed.  Owing  to  personal  peculiarities 
or  idiosyncrasies,  quinine  sometimes  causes  manifestations  entirely  unlike 
those  ordinarily  seen.  Thus,  in  a  case  reported  by  A.  Erlenmeyer,"  the 
symptoms  simulated  those  of  strychnine-poisoning,  f  In  some  persons  a 
few  grains  of  quinine  given  internally  produce  wide-spread  erythema  and 
subdermal  cedema,  affecting  it  may  be  the  whole  body,  but  usually  most 
pronounced  in  the  face,  and  accompanied  by  pronounced  disturbances 
of  the  nervous  system  and  circulation,  the  symptoms  usually  subsiding  in 
from  a  few  hours  to  a  few  days,  and  sometimes  being  followed  by  desqua- 
mation  of  the  cuticle. 

*  In  certain  regions  of  country  persons  suffering  from  malarial  poisons  have  inter- 
mittent attacks  of  haematuria,  or  probably,  to  speak  more  correctly,  of  methaemoglo- 
binuria,  in  which  the  haematuria  has  been  attributed  by  many  practitioners  to  the  influence 
of  the  quinine  sulphate.  The  facts,  however,  that  quinine  never  produces  methaemo- 
globinuria  in  healthy  individuals,  that  the  attacks  are  accompanied  by  chill,  fever,  and 
sweat,  following,  according  to  Carreau,  absolutely-the  course  of  the  paroxysm  of  inter- 
mittent fever,  and  that,  though  quinine  is  used  everywhere,  the  methaemoglobinuria 
occurs  only  in  certain  localities,  certainly  seem  to  prove  that  the  attacks  are  really  due  to 
a  peculiar  form  of  malaria  and  not  to  the  quinine.  The  most  elaborate  account  we  have 
met  with  is  that  published  in  Guadeloupe,  in  1891,  by  J.  Carreau  (La  Mlthlmoglobinurie 
Quinique,  1891  ;  see  also  Bull.  Soc.  de  Mid.  Pratique  de  Paris,  1891 ;  Arch,  de  Mid. 
Navale,  1896,  Ixv.,  1897,  Ixvii.  ;  Bull.  Therap.,  xcvii.) ;  Pispiris  (Le  Progres  Mid.,  1891, 
xix.)  affirms  that  in  some  cases  of  malarial  fever  not  only  the  internal  administration  but 
also  external  friction  of  the  quinine  sulphate  will  provoke  serious  gastro-intestinal 
hemorrhage.  It  does  not,  however,  appear  probable  that  the  quinine  in  his  cases  was 
the  cause  of  the  bleeding. 

t  For  cases,  see  Brit.  Med.  Journ.,  1869,  ii. ;  Berlin.  Klin.  Woch.,  1877,  294  ;  Phila. 
Med.  Times,  x.  166 ;  N.  Y.  Med.  Record,  xxi.  627. 


ANTIPERIODICS.  577 

The  importance  of  these  idiosyncrasies  was  shown  in  a  case  in  our  own  prac- 
tice, in  which  two  grains  given  by  the  mouth  produced  a  furious  general  urticaria, 
with  great  subdermal  swelling  and  cardiac  depression  of  the  most  alarming  charac- 
ter ;  according  to  B.  D.  Titlow,™  violent  general  erythema  involving  the  lymphatics 
was  produced  by  one-third  of  a  grain  of  quinine.  Miccich674  reports  the  death  of 
an  adult  caused  by  the  hypodermic  injection  of  seven  and  seven-tenths  grains  (one- 
half  gramme),  the  symptoms  being  great  paleness  of  the  surface,  small,  frequent 
pulse,  high  fever,  severe  nervous  depression,  increasing  stupor  with  delirium,  great 
dyspnoea,  jaundice,  haematuria,  and  anuria.  Death  occurred  on  the  seventh  day. 
Both  during  life  and  at  the  autopsy  the  evidences  of  great  destruction  of  red  blood- 
corpuscles  were  apparent.  Purpura  has  also  been  ascribed  to  the  alkaloid.75  Cheval- 
lier T6  describes  a  peculiar  affection  of  the  skin,  etc.,  as  occurring  among  workers 
in  the  bark. 

Fatal  instances  of  poisoning  by  quinine  are  rare  in  literature,  but 
Husemann  "  has  made  a  collection  of  cases  in  which  death  has  been  attrib- 
uted to  the  alkaloid, — not  always,  in  our  opinion,  with  correctness.  The 
minimum  fatal  dose  is  not  known,  but  must  be  very  large. 

Clapton78  details  a  case  in  which  a  soldier  took  at  one  dose  an  ounce  of  the 
sulphate,  stirred  up  in  some  water,  without  the  induction  of  any  more  serious  symp- 
tom than  a  mild  stupor  ;  a  similar  case  is  mentioned  by  Lente,  on  the  authority  of 
Woodhull  ;  and  a  third  is  recorded  by  Taussig.79  R.  G.  Wharton80  records  a  case 
in  which  during  thirty-six  hours  a  half-ounce  was  taken  without  vomiting  and  with- 
out ill  effect.  We  cannot  help  suspecting  that  in  all  of  these  cases  much  of  the 
drug  passed  through  the  intestines  without  absorption.  In  the  famous  case  of 
Bazire,  five  ounces  taken  in  the  course  of  ten  days  caused  death. 

Quinine  tannate*  although  not  official,  has  been  used  to  some  extent, 
and  is  not  altogether  inefficient.  It  has  the  great  advantage  of  not  being 
disagreeable  to  the  palate,  but  is  less  active  and  less  certain  than  the 
more  soluble  salts  of  the  alkaloid,  and  is  also  much  slower  in  its  operation. 
If  given  at  all,  it  should  be  in  doses  one-third  greater  than  those  of  the 
sulphate. 

QUINIDINJE  SULPHAS. — Quinidine  sulphate  occurs  in  long,  shin- 
ing, silky,  acicular  crystals,  soluble  in  one  hundred  parts  of  water  at 
59°  F.  It  probably  closely  resembles  quinine  in  its  physiological  and 
therapeutic  properties,  and  is  a  moderately  efficient  antiperiodic  ;  the  dose 
is  about  one-third  larger  than  that  of  quinine. 

CINCHONINjE  SULPHAS— CINCHONINJE  SULPHATE.     U.  S. 

The  pure  alkaloid  cinchonine  crystallizes  in  prisms  and  needles.  The 
official  cinchonine  sulphate  is  in  short  oblique  prisms  of  a  very  bitter 
taste,  soluble,  at  59°  F. ,  in  sixty-six  parts  of  water,  more  freely  in  boiling 
water,  readily  soluble  in  alcohol. 

*  For  an  elaborate  discussion  of  the  therapeutic  value  of  this  salt  see  Bulletin  de 
f  Academic,  Paris,  1872. 

37 


578  GENERAL  REMEDIES. 

PHYSIOLOGICAL  ACTION. — Conzen  (quoted  by  Husemann)  has  found 
that  the  action  of  cinchonine  on  infusoria  and  on  fermentation  is  simi- 
lar to  but  weaker  than  that  of  quinine,  and  that  on  the  movements 
of  the  white  blood-corpuscles  its  influence  seems  transient.  It  is  stated 
that  it  is  eliminated  unchanged  and  rapidly,  the  great  bulk  of  it  being 
thrown  off  in  the  first  twenty-four  hours.  According  to  the  experiments  of 
Laborde 81  and  Bochefontaine,82  toxic  doses  cause  in  the  lower  animals  more 
violent  epileptiform  convulsions  than  do  the  corresponding  doses  of 
quinine.  In  Bochefontaine' s  experiments  the  relative  strength  of  cincho- 
nine to  quinine  was  about  10  to  16,  in  Bernatzik's  (on  dogs  only)  as  4 
to  5.  De  Schweinitz  has  found  that  cinchonine  produces  amaurosis  in 
the  dog,  as  does  quinine. 

THERAPEUTICS. — As  an  antiperiodic,  cinchonine  exerts  a  similar  in- 
fluence to  quinine,  but  is  probably  about  one-third  weaker  than  that  alka- 
loid, and  must  be  used  in  correspondingly  larger  dose.  J.  B.  Hamilton 
affirms  as  the  result  of  experiment  that  cinchonine  as  a  prophylactic 
against  malaria  is  even  superior  to  quinine.  As  a  tonic  we  have  never 
been  able  to  perceive  that  cinchonine  acts  differently  from  quinine. 

CINCHONIDIN^E  SULPHAS.  U.  S. — Cinchonidine  sulphate  occurs  in 
white,  silky,  lustrous  needles  or  prisms,  odorless,  of  a  very  bitter  taste, 
soluble  in  seventy  parts  of  water,  freely  soluble  in  acidulated  solutions. 
It  polarizes  to  the  left,  and  is  not  fluorescent.  According  to  Se"e  and 
Bochefontaine,85  cinchonidine  produces  in  the  lower  animals  symptoms 
similar  to  those  caused  by  quinine,  except  that  the  convulsions  are  less 
severe.  A  boy  aged  five  years  took  one  hundred  and  twenty-eight  grains 
in  solution  during  six  hours  without  vomiting.  There  were  then  convul- 
sions followed  by  great  collapse,  fall  of  temperature,  pulselessness  (with 
seventy-four  cardiac  beats  per  minute),  dilated  pupils,  muscular  relaxa- 
tion, and,  finally,  death  ;  consciousness  was  preserved  to  the  end.* 

PHYSIOLOGY  AND  THERAPEUTICS. — Cinchonidine  acts  similarly  to 
quinine,  but  is  less  powerful,  doses  one-third  greater  being  required. 
The  assertions  made  by  various  clinicians,  that  it  produces  less  disagree- 
able symptoms  than  does  quinine,  have  not  been  confirmed.  De  Segrais88 
has  found  the  bromohydrate  given  hypodermically  in  doses  of  four  to  six 
grains  (0.26-0.4  Gm. )  very  efficacious. 

CINCHONAMINE. — This  alkaloid  was  discovered  by  Arnaud84  in  the  Cuprea 
bark  from  Colombia,  probably  the  product  of  Remijia  pedunculata  and  Remijia 
Purdieana.  In  poisonous  doses  it  produces  violent  convulsions  in  the  dog,  with 
fall  of  the  arterial  pressure.  It  also  arrests  the  heart  in  diastole,  and  increases 
especially  the  secretion  of  the  salivary  glands.  (Se"e  and  Bochefontaine. )  Its  influ- 
ence upon  man  has  not,  so  far  as  we  are  aware,  been  studied,  but  its  botanical  an  J 
chemical  relations  make  it  probable  that  it  resembles  quinine  in  its  physiological 
and  therapeutical  properties. 

*  See  N.  Y.  Med.  Journ.,  1884,  xxxix. 


ANTIPERIODICS.  579 

WARBURG'S  TINCTURE. — This  is  a  dark  brown  liquid,  prepared  in  accordance 
with  a  very  complicated  formula,*  which  has  obtained  an  extraordinary  reputation 
in  India  and  other  tropical  countries  in  the  treatment  of  severe  remittent  and  malig- 
nant malarial  fevers.  The  testimony  is  so  strong  as  to  its  remarkable  and  almost 
certain  efficiency  that  it  cannot  be  questioned,  and  entitles  the  tincture  to  rank 
above  all  other  remedies.  The  method  of  administration  is  as  follows.  The 
bowels  having  been  freely  opened,  a  half-ounce  of  the  tincture  is  given  undiluted, 
all  drink  being  withheld,  and  at  the  end  of  three  hours  a  second  half-ounce  is  in 
similar  manner  exhibited.  Soon  after  the  last  dose  a  profuse  and  very  aromatic 
perspiration  sets  in,  and  convalescence  is  usually  secured.  The  remedy  is  also 
commended  in  one-drachm  dose  in  acute  nervous  exhaustion  and  collapse  without 
organic  disease. 

QUININE  ESTERS. — A  number  of  the  esters  of  quinine  have  been  ex- 
amined pharmacologically,  and  some  of  them  have  found  their  way  into 
practical  use.  Among  these  compounds  acetylquinine  has  been  con- 
demned on  account  of  its  taste  ;  benzoylquinine  and  phosphorylquinine 
are  stated  by  M.  Overlach100  to  be  practically  inert.  The  esters  which 
have  been  put  upon  the  market  as  of  value  are  as  follows  : 

ARISTOCHIN. — Neutral  carbonic  quinic  ester. — This  tasteless,  pinkish-white, 
amorphous  powder,  soluble  in  alcohol,  ether,  chloroform,  or  glycerin,  insoluble  in 
water,  is  said  to  contain  ninety-six  per  cent,  of  quinine.  According  to  Stursberg,101 
after  its  ingestion,  quinine  appears  in  a  short  time  freely  in  the  urine.  It  probably 
is  effective  as  an  antiperiodic,  but  has  been  chiefly  commended  in  whooping-cough 
of  children,  given  in  doses  of  from  one  to  four  grains  three  times  a  day. 

EUQUININE. — The  ethyl  carbonic  ester  of  quinine  has  been  highly  commended 
as  a  substitute  for  quinine,  and  as  having  the  advantage  of  being  practically  tasteless 
and  of  producing  a  less  severe  tinnitus  aurium.  The  tinnitus  aurium  is,  however, 
almost  certainly  a  test  of  the  amount  of  active  quinine  in  the  circulation  ;  that 
euquinine  is  absorbed  very  slowly  and  eliminated  very  slowly  is  indicated  by  the 
studies  of  F.  K.  Kleine,  who  was  unable  to  obtain  from  the  urine  more  than  seven- 
teen per  cent,  of  the  quinine  contained  in  the  ingested  euquinine.  It  does  not, 
therefore,  appear  probable  that  euquinine  is  as  efficient  as  quinine,  but  it  has  been 
commended  highly  in  all  forms  of  malarial  disease,  also  in  whooping-cough,  chorea, 
an&mia,  general  debility,  and,  indeed,  in  all  affections  for  which  quinine  is  gener- 
ally employed.  According  to  Luigi  de  Carlo,  combined  with  benzonaphthol  it  is 
especially  effective  in  those  forms  of  malaria  accompanied  by  intestinal  affection. 
From  fifteen  to  thirty  grains  may  be  given  in  the  course  of  the  twenty-four  hours. 

RHEUMATINE. — Salicylate  of  salicyl-quinine  occurs  in  white,  tasteless  needles  ; 
sparingly  soluble  in  water.  It  has  been  especially  commended  by  Overlach  in  the 
treatment  of  rheumatic  neuritis.  It  is  affirmed  also  to  relieve  the  lancinating  pains 
of  tabes,  and  may  be  given  in  doses  of  fifteen  grains  up  to  a  drachm  in  the  course 
of  twenty-four  hours. 

SALOOUININE. — This  quinic  ester  of  salicylic  acid  occurs  in  colorless  crystals, 
insoluble  in  water,  but  soluble  in  alcohol  and  ether.  It  contains  fifty  per  cent,  of 
quinine.  Overlach  alleges  that  it  does  not  cause  cinchonism  ;  it  is,  therefore,  prob- 
ably as  an  antiperiodic  very  feeble,  a  conclusion  which  is  confirmed  by  the  fact  that 

*  For  formula,  see  United  States  Dispensatory,  i8th  ed. 


580  GENERAL  REMEDIES. 

F.  K.  Kleine  was  only  able  to  recover  during  the  twenty-four  hours  from  two  to 
seven  per  cent,  of  the  quinine  contained  in  an  ingested  dose  of  saloquinine.  Never- 
theless, saloquinine  has  been  most  highly  commended  as  an  antiperiodic,  as  an  anti- 
pyretic in  fevers,  and  as  an  analgesic  and  antirheumatic  in  neuralgias,  neuritis,  and 
similar  conditions.  It  has  usually  been  given  in  the  single  dose  of  thirty  grains.  In 
sciatica  and  various  neuralgias  the  dose  may  be  repeated  within  the  twenty-four 
hours.  The  absorption  of  the  drug  appears  to  be  very  slow,  so  that  in  typhoid 
fever  thirty  grains  of  it,  administered  directly  after  the  cold  bath,  begins  to  exert  its 
influence  about  the  time  the  effect  of  the  bath  is  passing  off. 

METHYLTHIONIN^    HYDROCHLORIDUM— 
METHYLENE-BLUE.     U.  S. 

Medicinal  methylene-blue  is  to  be  carefully  distinguished  from  the  dye- 
stuff,  which  is  a  mixture  of  the  chloride  of  zinc  and  tetramethylthionine, 
and  contains  various  impurities  of  which  the  most  important  is  arsenic. 
When  intended  for  internal  use  the  drug  must  be  free  from  arsenic  and 
zinc.  Parenski  and  Blatteis l  attribute  the  various  unpleasant  symptoms 
— nausea,  vomiting,  strangury,  and  the  like — which  have  been  reported, 
to  the  confusion  of  the  medicinal  with  the  dye  methylene-blue. 

Absorption  and  Elimination. — Methylene-blue  is  readily  absorbed 
from  both  the  subcutaneous  tissues  and  mucous  membranes  of  the  ali- 
mentary tract,  appearing  in  the  urine,  according  to  Achard  and  Cas- 
taigne,2  within  half  an  hour  after  its  hypodermic  injection.  Although 
the  bulk  of  the  drug  ingested  probably  escapes  with  the  urine,  the  bluish 
saliva  and  faeces  observed  by  Ehrlich  and  Leppmann s  would  indicate  that 
other  glands  share  in  its  elimination. 

In  a  number  of  morbid  conditions  the  urine  does  not  become  dis- 
colored after  the  administration  of  methylene-blue. 

Achard  and  Castaigne,  believing  that  this  was  due  to  failure  of  elimination, 
suggested  the  remedy  as  a  test  for  the  permeability  of  the  kidney  and  reported  a 
number  of  cases  of  nephritis  tending  to  support  their  position.  Subsequently, 
however,  Voisin  and  Hauser*  showed  that  if  this  colorless  urine  be  warmed,  or  if 
acetic  acid  be  added  to  it,  the  blue  color  will  appear.  Achard  and  Castaigne,5  in 
reply  to  this,  expressed  the  opinion  that  methylene-blue  was  eliminated  in  part 
unchanged,  and  in  part  as  a  colorless  chromogenic  substance,  and  that  the  diseased 
kidney  permitted  the  passage  of  the  latter  but  not  of  the  methylene-blue  itself ;  they 
give,  however,  no  indication  of  the  chemical  nature  of  this  chromogen. 

General  Action. — Very  little  is  known  concerning  the  physiological 
action  of  methylene-blue.  According  to  Combemale  and  Francois6  doses 
of  0.4  gramme  per  kilo  produced  in  the  dog  vomiting,  purging,  and 
diuresis.  These  observers  found  that  in  the  guinea-pig  o.  3  gramme  per 
kilo  caused  muscular  weakness,  greatly  accelerated  respiration,  and  death. 
After  death  there  was  widespread  staining  of  the  tissues,  especially  marked 
in  the  nervous  system.  The  blood  was  chocolate-colored  and  contained 
methaemoglobin. 

THERAPEUTICS. — In  1890  Ehrlich  and  Leppmann  called  attention  to 
the  analgesic  action  of  methylene-blue,  reporting  several  cases  of  neural- 


ANTIPERIODICS.  581 

gic  and  rheumatic  pains  relieved  by  it.  Combemale  and  Francois  found 
that  while  in  simple  neuralgia  it  was  frequently  of  service,  in  neuritis  and 
central  nerve-pains  it  was  of  little  value.  Although  numerous  other 
authors  have  confirmed  the  statement  that  methylene-blue  possesses 
some  analgesic  action,  the  drug  seems  to  be  uncertain  in  its  effect,  and 
has  no  advantage  over  the  newer  aniline  derivatives.* 

As  an  antiperiodic,  methylene-blue  deserves  a  position  of  high  rank, 
rivalling  quinine  in  the  treatment  of  malaria.  In  four  hundred  and 
twenty-five  cases  collected  by  H.  C.  Wood,  Jr.,7  in  which  it  was  the  sole 
drug  employed,  there  were  85  per  cent.  (362)  of  recoveries.  Both  Rosin 8 
and  Iwanoff 9  have  shown  that  it  exerts  a  direct,  destructive  action  on  the 
plasmodium  malariae.  The  latter  observer  states  that  this  effect  is 
most  marked  in  the  adult  forms  of  the  protozoon,  in  this  contrasting 
strongly  with  quinine  (correct  (?);  see  p.  572,  small  print),  and  that  the 
crescent  type,  notoriously  resistant  to  cinchona,  is  easily  destroyed  by 
methylene-blue.  Since  it  exerts  no  irritant  influence  on  renal  structure 
methylene-blue  has  been  recommended  especially  in  the  so-called  black- 
water  fever.  Whenever  in  a  malarial  disease  quinine  is  contra-indicated 
it  is  the  most  serviceable  substitute  we  possess. 

Austin  Flint  (1895),  impressed  with  the  results  obtained  from  the  use 
of  methylene-blue  in  cases  of  chyluria,  suggested  its  use  in  gonorrhoea, 
concluding  from  its  action  on  the  genito-urinary  tract  that  it  would  prove 
to  be  a  valuable  remedy  in  that  affection.  The  results  obtained  at  the 
hands  of  many  clinical  observers  do  not,  however,  confirm  this  opinion, 
experience  showing  that  where  the  remedy  is  employed  alone,  and  not  in 
combination  with  well  recognized  antiblenorrhagic  drugs,  it  has  no  effect 
whatever  in  lessening  the  urethral  discharge.  The  property  which  the 
drug  possesses  of  coloring  the  urine  is,  moreover,  a  distinct  disadvantage, 
as  it  prevents  the  physician  from  drawing  proper  conclusions  regarding 
the  natural  appearance  of  the  urine.  Methylene-blue  may  be  set  down  as 
a  mild  genito-urinary  antiseptic  of  some  value  in  chronic  cystitis  and 
pyelitis.  f 

ADMINISTRATION. — In  the  treatment  of  malarial  diseases  with  methyl- 
ene-blue it  is  necessary  to  continue  the  use  of  the  drug  for  some  time 
after  the  cessation  of  symptoms  on  account  of  the  liability  of  relapse. 
From  two  to  three  grains  (0.1-0.2  Gm. )  may  be  given  every  three 
hours  for  ten  days,  and  after  this,  three  grains  three  times  a  day  for  a 
fortnight  longer.  In  gonorrhoea  the  usual  dose  is  two  or  three  grains 
(0.1-0.2  Gm. )  three  times  a  day.  The  remedy  may  be  conveniently 
given  in  pill  form,  but  preferably  enclosed  in  gelatin  capsule  to  avoid  the 
staining  of  the  fingers  and  lips.  The  patient  should  always  be  warned  of 
the  probable  discoloration  of  the  urine. 

*  The  theory  of  Ehrlich  that  methylene-blue  acts  as  analgesic  by  staining  the  axis 
cylinders  has  been  shown  by  Combemale  and  Francois  to  be  untrue,  for  while  it  is  pos- 
sible to  stain  living  tissue  with  the  drug,  doses  far  in  excess  of  those  used  are  necessary. 

f  This  paragraph  was  written  by  Prof.  H.  M.  Christian. 


582  GENERAL  REMEDIES. 

EUCALYPTUS.     U.  S. 

Of  the  Australian  genus  Eucalyptus,*  which  comprises  about  one  hun- 
dred and  thirty-five  species  of  evergreen  trees,  the  U.  S.  Pharmacopoeia 
recognises  only  E.  globulus,  whose  leaves  are  official,  but  allows  the  oil  of 
eucalyptus  (OLEUM  EUCALYPTI,  U.  S. )  to  be  distilled  from  fresh  leaves 
of  various  species  of  the  genus.  Neither  the  dried  leaves  nor  their  fluid 
extract  (FLUIDEXTRACTUM  EUCALYPTI,  U.  S. )  are  themselves  used  in 
medicine.  From  the  various  species  of  Eucalyptus  are  prepared  in 
Australia  an  umber  of  volatile  oils,  and  also  the  Eucalyptus  Gum  of  the 
British  Pharmacopoeia.  The  so-called  red  gum,  which  occurs  in  commerce 
in  kino-like  grains  or  masses,  contains  nearly  five  per  cent,  of  tannic  acid, 
and  is  much  used  in  making  astringent  lozenges. 

Most  of  the  eucalyptus  oils  are  composed  very  largely  of  eucalyptol 
or  of  phellandrene.  The  oils  containing  phellandrene  were  thrown  out  by 
the  revisers  of  the  U.  S.  Pharmacopoeia,  evidently  under  the  impression 
that  the  active  physiological  portion  of  the  oil  is  eucalyptol.  Concerning 
the  physiological  action  of  phellandrene,  however,  we  have  no  knowledge. 

Oil  of  eucalyptus  is  a  colorless  or  faintly  yellowish  liquid,  having  a 
characteristic  somewhat  camphoraceous  odor  and  a  spicy,  disagreeable 
taste.  Dose,  ten  to  fifteen  minims  (0.6-0.9  C.c. ),  in  capsules.  Its  active 
principle  (  EUCALYPTOL,  U.  S. )  is  to  be  preferred  to  the  oil  as  more  con- 
centrated and  uniform  in  action.  Dose,  five  to  ten  minims  (0.3-0.6  C.c.). 
All  the  virtues  of  Eucalyptus  probably  reside  in  the  volatile  oil,  which  is 
in  greatest  abundance  in  the  leaves,  f 

PHYSIOLOGICAL  ACTION. — Local  Action. — Absorption  and  Elimi- 
nation.— The  oil  of  eucalyptus  is  decidedly  irritant,  large  doses  causing 
burning  in  the  mouth  and  fauces,  with  increased  secretion  of  saliva,  fol- 

*  Attention  was  first  called  by  Labillardiere  in  1792  to  the  value  of  the  Eucalyptus 
globulus,  but  it  was  not  until  1860  that  M.  Ramel  commenced  the  culture  of  the  tree  in 
Paris  and  induced  the  Prefect  of  the  Seine  to  order  its  cultivation  on  a  large  scale.  Since 
that  time  it  has  been  largely  introduced  into  Europe,  Algeria,  South  Africa,  and  California, 
and  in  some  of  these  countries  planted  forests  are  now  growing  and  spreading.  The  tree 
is  remarkable  for  combining  extreme  hardness  of  wood  with  a  rapidity  of  growth  asserted 
to  be  about  five  times  that  of  our  ordinary  trees  ;  it  is  also  affirmed  that  shingles  made  of 
it  are  fire-proof.  Its  capability  for  absorbing  and  evaporating  water  is  extraordinary,  and 
to  it  has  been  attributed  the  freedom  of  Australia  from  malarial  climatic  influences.  In- 
deed, it  is  stated  that  a  tree  will  evaporate  ten  times  its  weight  of  water  in  twenty-four 
hours,  and  numerous  examples  are  given  in  which  swamps  in  Europe  and  Algeria  have 
been  rapidly  converted  by  it  into  dry  ground.  It  is  believed  to  destroy  malaria  not  only  by 
draining  the  soil,  but  also  by  yielding  balsamic  exudations  to  the  air;  however  this  may 
be,  there  is  at  present  very  strong  evidence  as  to  its  power  of  rendering  infected  districts 
healthy.  As  the  consideration  of  this  subject  belongs  to  hygiene  rather  than  to  therapeu- 
tics, the  reader  is  referred  for  detailed  information  to  the  following  memoirs :  Regulus 
Carlotti  (L' Eucalyptus,  son  Rang  parmi  les  Agents  de  la  Matters  Medicale,  Ajaccio, 
1872),  M.  Gimbert  (L' Eucalyptus  Globulus,  son  Importance  en  Agriculture,  en  Hygiene, 
et  en  Medecine,  Paris,  1870),  Waterer  {Bulletin  de  la  Societe  d'Acclimatation,  1872; 
London  Medical  Record,  Dec.  1873;  London  Lancet,  1877,  ii.). 

Under  the  name  of  Eucalypsinthe ,  a  liqueur  distilled  from  the  leaves  of  the  euca- 
lyptus has  appeared  in  European  commerce. 

t  It  has  been  affirmed  that  the  leaves  of  Eucalyptus  contain  also  an  alkaloid ;  but 
Rabuteau  (Bull.  Therap.,  Ixxxiii.  549)  has  demonstrated  that  this  is  an  error. 


ANTIPERIODICS.  583 

lowed  very  soon  by  a  feeling  of  warmth  in  the  stomach.  It  is  absorbed 
from  the  alimentary  canal,  and  is  probably  eliminated  by  the  lungs,  skin, 
and  kidneys.  In  the  experiments  of  Binz,  the  day  after  the  ingestion  of 
seventy-five  drops  the  breath  smelt  of  the  drug  and  the  perspiration  of 
amylic  alcohol ;  the  urine  began  to  have  the  odor  of  the  oil  an  hour 
and  a  half  after  its  ingestion,  and  continued  to  have  it  for  thirty-six  hours. 
Gimbert1  states  that  the  odor  imparted  to  the  urine  resembles  that  of 
violets,  and  is  very  similar  to  that  caused  by  turpentine.  Binz  affirms  that 
upon  the  lower  infusoria  the  oil  acts  even  more  powerfully  than  does  qui- 
nine, and  its  general  antiseptic  properties  are  decided  (Gimbert). 

General  Effect. — The  constitutional  effect  of  the  same  dose  of  the  oil 
appears  to  vary  considerably  in  different  individuals  ;  but  the  following 
summary  comprises  the  facts  as  nearly  as  may  be.  After  the  ingestion  of 
from  ten  to  twenty  minims,  a  period  of  mental  and  physical  activity  is  often 
apparent,  followed  by  a  feeling  of  calm  and  serenity.  After  large  doses 
irritation  of  the  digestive  organs  sometimes  shows  itself  by  loose  stools  or 
even  by  vomiting.  In  exceptional  cases  even  the  moderate  dose  may 
produce  violent  cardiac  palpitation  and  intense  headache  and  fever,  all 
these  symptoms  probably  being  due  to  gastric  irritation.  Large  amounts 
of  the  oil  cause  marked  depression,  with  slowing  and  afterwards  quickness 
and  weakness  of  the  pulse,  general  asthenia,  sub-normal  temperature, 
blunting  of  sensation,  and  finally  profound  loss  of  muscular  power  with 
stupor,  deepening  into  unconsciousness,  and  accompanied  by  loss  of  the 
reflexes,  and  contracted  reactionless  pupil. 

In  anomalous  cases  the  symptoms  produced  by  the  oil  of  eucalyptus  differ  from 
the  typical  character.  Thus,  in  an  old  man  who  took  eighty  drops,  the  power  of 
motion  almost  disappeared  ;  the  man  also  affirmed  that  he  lost  for  the  time  being 
all  sense  of  the  presence  of  his  limbs,  so  that  he  was  unconscious  of  possessing 
them  when  he  shut  his  eyes,  although  his  intellect  was  perfectly  clear  throughout. 
In  a  case  reported  by  Alfred  Neale,2  a  little  over  half  an  ounce  of  the  oil  of  eucalyp- 
tus is  said  to  have  produced  death  in  fifteen  hours  in  a  healthy  boy  :  the  only  re- 
corded symptoms  were  violent  dyspnoea  with  collapse.* 

Upon  the  lower  mammalia  the  oil  of  eucalyptus  appears  to  act  precisely  as  it 
does  on  man.  According  to  the  experiments  of  Gimbert,  the  hypodermic  injection 
of  the  oil  is  immediately  followed  by  a  period  of  excitement,  seemingly  in  great 
measure  due  to  the  intense  local  irritation ;  after  about  half  an  hour,  if  the  dose 
has  been  sufficiently  large,  the  animal  begins  to  stumble  and  totter  in  walking,  the 
breathing  grows  more  and  more  slow  and  irregular,  the  limbs  give  way,  the  ears 
droop,  the  muscular  weakness  becomes  profound,  and  death,  preceded  often  by 
partial  convulsions,  occurs  through  failure  of  respiration. 

Death  appears  to  be  produced  by  the  fatal  dose  through  asphyxia. 
According  to  the  experiments  of  Gimbert  (confirmed  by  Binz),  the  motor 
nerves  and  the  muscles  are  not  affected,  so  that  the  failure  of  motion  and 
reflex  activity  is  probably  due  to  a  depression  of  the  motor  side  of  the 
spinal  cord  and  of  the  medulla.  According  to  Hermann  Schlager,  the 

*  As  a  quart  of  very  bloody  serum  was  found  in  the  pleura  cavity,  and  as  the  boy 
was  not  seen  professionally  until  he  was  in  articulo  mortis,  doubt  attaches  to  this  case. 


584  GENERAL  REMEDIES. 

hypodermic  injection  of  the  oil  produces  a  temporary  rise  of  temperature, 
probably  as  the  result  of  the  local  irritation,  but  after  toxic  doses  the 
temperature  falls  decidedly.  Schlager3  also  states  that  the  large  dose 
of  the  oil  causes  a  marked  lessening  of  the  arterial  pressure,  whose 
coming  on  is  not  affected  by  previous  section  of  the  vagi,  by  atropinization 
of  the  heart  or  by  section  of  the  cord.  It  would  appear,  therefore,  that 
the  oil  of  eucalyptus  directly  depresses  the  heart  or  the  peripheral  ar- 
teries. As  in  Schliiger's  experiments  the  force  of  the  isolated  frog's  heart 
was  distinctly  depressed  by  the  drug,  the  latter  must  be  a  direct  cardiac 
depressant.  Mosler 4  affirms  that  in  dogs  whose  spleens  were  exposed, 
injections  of  tincture  of  the  leaves  of  eucalyptus  produced  a  decided  con- 
traction of  the  viscus.  According  to  Gimbert,  the  excretion  of  urea  is 
enormously  increased  by  the  drug. 

THERAPEUTICS. — The  oil  of  eucalyptus  has  some  power  as  an  anti- 
periodic,  but  is  much  inferior  to  the  cinchona  alkaloids  and  to  methylene- 
blue,  and  should  be  used  only  in  cases  in  which  for  sufficient  reasons  these 
remedies  cannot  be  employed,  or  as  an  adjuvant  to  them. 

Joseph  Keller 5  used  it  in  four  hundred  and  thirty-two  cases,  of  which  two  hun- 
dred and  ninety-three  had  suffered  from  previous  attacks.  Of  the  tertians  75.57 
per  cent.,  of  the  quartans  70  per  cent.,  and  of  the  quotidians  67.89  per  cent,  yielded 
to  the  remedy.  He  recommends  it  as  especially  valuable  in  obstinate  cases  in 
which  quinine  has  been  taken  again  and  again.  Lorinser,6  Haller,7  Bohn,8  Carlotti, 
Cortan,'  Gimbert,  Gubler,  Tristany,10  of  Spain,  J.  H.  Musser,"  and  others,  bear 
testimony  to  the  power  of  Eucalyptus  in  malarial  diseases  ;  while  Brudell,1*  Seitz," 
and  Papillon  "  affirm  it  to  be  of  little  or  no  value. 

Oil  of  eucalyptus  is  one  of  the  best  stimulating  expectorants  that  we 
possess  :  in  both  acute  and  chronic  bronchitis  it  may  be  exhibited  when 
there  is  free  secretion.  Children  bear  it  very  well.  According  to  A.  F. 
Galbraith  Faulds,15  it  is  valuable  in  some  forms  of  glycosuria.  Dose  of 
oil  or  of  eucalyptol  three  to  ten  minims  every  three  to  five  hours. 


REFERENCES. 

CINCHONA.  14.  CERNA P.  M.  T.,  x.  493. 

1.  KKRNER A.  G.  P.,  1870,  iii.  93.  15.  CHAPERON  .   .   .   .  A.  G.  P.,  1869,  295. 

2.  BRIQUET     ....  Traite    therap.    de    Quin-  16.  SEDGWICK  .   .   .   .  J.  P.,  iii.  22. 

quina,  Paris,  1855.  17.  ROBERT A.  E.  P.  P.,  xv.  49. 

3.  DE  RENZI    .   .   .   .  B.  G.  T.,  xci.  45.  18.  WILD B.  M.  J.,  1887,  ii. 

4.  DIETL W.  M.  W.,  1852.  19.  PIORRY A.  G.  M.,  1847. 

5.  LANDERER     .   .   .  Repertorium  f.  Pharmacia,  20.  SCHLOCKOW  .   .   .  De   Chini    Sulfavici,   etc., 

1836,  1839,  1842.  Bratisl.,  1860. 

6.  WELITSCHKOWSKI  .  St.      Petersburg      Med.  21.  SCHROFF     ....  Med.  Jahrb.,  1875. 

Wochensch.,  1876.  22.  JERUSALIMSKY  .   .  C.  M.  W..  1876,  476. 

7.  JAKOUBOWICH   .   .Rev.    d.    Sciences    Med.,  23.  SEE  and  BOCHEFONTAINE  .  C.  R.  A.  S.,  xcvi. 

1873.  267. 

S.  ALBERTONI    .   .   .  A.  E.  P.  P.,  xv.  278.  24.  SCHARRENBROICH  .  In.  Dis.,  Bonn,  1867. 

9.  DUPUIS L'Action  Physiol.  de  Qui-  25.  KERNER Pract.,  vii.  321. 

nine,  Paris,  1877.  26.  GELTOWEKY  .   .   .  Pract.,  vii. 

jo.  KIRCHNER  ....  Sitzungsb.  d.   Phys.  Med.  27.  BINZ V.  A.  P.  A..  1869,  xlvi.  138. 

Gesellsch.,      Wurzburg,  28.  CUTTER Psychol.  Med.-Legal  Jour- 

1881,  161.  iial.  Feb.  1875. 

11.  ROOSA A.  J.  M.  S.,  1874.  29.  HARE P.  M.  T.,  xv.  43. 

12.  EULENBURG  .   .   .  A.  A.  P.,  1865.  30.  MARTIN In.  Dis.,  Gicssen,  1868. 

13.  HEUBACH    .   .    .   .  C.  M.  W.,  1874,  674.  31.  BINZ A.  E.  P.  P.,  1873,  i. 


57. 


ZUNST In.  Dis.,  Bonn,  1886. 

SCHULTE     .  .   .   .  C.  M.  W.,  1871. 
RANSONE     ....  In.  Dis.,  Bonn,  1871. 
BRUNTON  and  CASH  .  St.  Barthol.  Hosp.  Rep., 

xviii.  269. 
MONTEVERDI    .   .  Ann.  et  Bull,  de  la  Soc.  de 

M6d.    de    Gand,    May, 

1871. 
WILSON Southern  Med.  and  Surg. 

Journ.,    1855,  341 ;   Sept. 

1860. 
WEST Savannah  Journ.  of  Med., 

i.  19. 

RANCILLIA     .   .   .  L'Union  Med.,  1873. 
SAVRE American         Practitioner, 

1871,  260. 
CHIARA L'Union    Med.,    Nov.    20, 

1873. 
WALRAVEN    .  .   .  B.  M.  S.  J.,  1873. 

BURT Med.  and  Surg.  Rep.,  1870. 

ERWIN     .   .       .   .  St.  L.  M.S.  J.,  March,  1872. 

HARRIS American  Pract.,  1872. 

RUSSWURM     .  .  .  American  Pract.,  1871,  127. 
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BOSSH In.  Dis.,  Dorpat,  1862. 

STRASSBURG  .  .  .  A.  E.  P.  P.,  ii.  343. 
UNRUH V.  A.  P.  A.,  1869,  xlviii. 

227. 

OPPENHEIM    .  .  .  A.  G.  P.,  1880,  xxxiii.  446. 
RABUTEAU  .  .   .   .  B.  G.  T.,  Ixxv.  475. 
VON  BOECK    .   .   .  Untersuchungen  iiber  die 

Zersetzung  d.  Eiweisses, 

etc.,  Munich,  1871. 

PRIOR A.  G.  P.,  xxxiv.  237. 

BOECK  and  BAUER  .  Z.  Bi.,  x. 
CHITTENDEN    .   .  S.  L.  P.  C.  Y.,  ii.  223. 
LIEBERMEISTER  .  D.  A.  K.  M.,  1867,  iii. 
LONDON  CLINICAL  SOCIETY  .  Transact.,  1870, 

iii.  201. 
NAUNYN  and  QUINCKE  .  A.  A.  P.,  1869. 

BINZ Pract.,  1870,  4. 

HARE B.  M.  S.  J.,  cxiv.  73. 

HAMILTON     .  .  .  Indian  Med.  Gaz.,  Nov.  i, 

1873- 

HENKE D.  A.  K.  M.,  xii.  630. 

BINZ Amer.    Journ.    Obst.    and 

Dis.  of  Women,  iii. 
LETZERICH    .  .   .  Amer.  Journ.   Obst.,  etc., 

iv.  761. 
DAWSON Amer.  Journ.  Obst.,  etc., 

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ALBHRTONI  and  CIOTTO  .  B.  G.  T.,  xc.  403. 

L.  L.,  1876,  i. 
FRIEDMANN  .   .   .  Wien.  Med.  Presse,  1884. 

DEWEES U.  M.  M..  1890. 

ERLENMEYER   .   .  Centralbl.  f.  Nervenheilk., 

June,  1890. 

TITLOW N.  Y.  M.  R.,  1898,  liv. 

MICCICHE  .  .   .  .  S.  Jb.,  ccxlix. 

B.  M.  S.  J.,  cix.  587. 
CHEVALLIER     .  .  Gaz.  des  H6p.,  1850. 
HUSEMANN    .   .   .  Th.  M.,  Jan.  1888. 
CLAPTON     .  .  .  .  M.  T.  G.,  April.  1864. 
TAUSSIG Stillg's     Therapeutics,    i. 

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WHARTON  .   .   .  .  A.  J.  M.  S.,  April,  1844. 
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ANTIPERIODICS. 

REFERENCES. —  Continued. 

82. 


585 


BOCHEFONTAINE  .  C.  R.  A.  S.,  XCvi.  503. 

83.  DE  SEGRAIS     .   .  A.  G.  M.,  xvii.  711. 

84.  ARNAUD     .   .   .   .  C.  R.  A.  S.,  xciii. 

85.  SEE  and  BOCHEFONTAINE  .  C.  R.  A.  S.,  c. 

86.  GRUENING    .  .  .  N.  Y.  Eye  and  Ear  Infirm. 

Rep.,  1897,  v.  6. 

87.  MELLINGER     .  .  Klin.  Monatsbl.  f.  Augen- 

heilk.,  1887,  xxv.  57. 

88.  DE  SCHWEINITZ  .  Toxic  Amblyopias,  1896; 

also  Ophthal.  Rec.,  1898, 
vii. ;  Ibid.,  1899,  viii.  610. 

89.  BARABASCHEW    .  Archiv      f.     Augenheilk., 

1891,  xxiii.  Heft  2. 

90.  DE  BONO  ....  Archiv  di  Ottal.,  1894,   ii. 

171-227;  Ibid.,    1899,    vi. 
398. 

91.  HOLDEN    ....  Transact.  Amer.  Ophtha). 

Soc.,  1897-98,  viii.  405. 

92.  DRUAULT  ....  Recherches  sur  la  Patho- 

g£nie     de      1'Amaurose 
Quinique,  Paris,  1900. 

93.  MAUREL    ....  A.  M.  Ex.,  1903,  xv. 

94.  WlTTMAACK     .    .  A.  G.  P.,  1903,  XCV. 

95.  GOLGI Rend     Inst.,     Lombardo, 

xxv. 

96.  MONACO  and  PANICHI  .  A.  I.  B.,  1900,  iii. 

97.  MERKEL   .  .  .  .  A.  E.  P.  P.,  1902,  xlvii. 

98.  KLEINE Z.  H.  I.,  xxxviii. 

99.  AUFRECHT    .  .  .  T.  M.,  1903. 

100.  OVERLACH     .     .     .  C.  I.  M.,  1901. 

101.  STURSBERG  .  .   .  M.  M.  W.,  1902,  xlix. 

METHYLENE-BLUE. 

1.  PARENSKI  and  BLATTEIS  .  Th.  M.,  1893,  vii. 

16. 

2.  ACHARD  and  CASTAIGNE  .  B.  S.  M.  H..  1897, 

xir.  637. 

3.  EHRLICH  and  LEPPMANN  .  D.  M.  W.,  1890, 

xvi.  493. 

4.  VoisiNand  MAUSER  .  G.  H.  M.  C.,  1897,  xliv. 

493- 

5.  ACHARD  and  CASTAIGNE  .  B.  S.  M.  H.,  1897, 

xiv.  1128. 

6.  COMBEMALE  and  FRANCOIS  .  C.  R.  S.   B., 

1890,  ii.  468;  1891.  iii.  300. 

7.  WOOD,  JR.    .   .   .  Tr.  P.  C.  M.,  Nov.  9, 1904. 

8.  ROSIN D.  M.  W.,  1893,  xix.  1068. 

9.  IWANOFF  .   .    .    .  D.  M.  W.,  1901,  xxvii.  291. 

EUCALYPTUS. 

1.  GIMBERT  ....  A.  G.  M.,  1873,  xxi.  141. 

2.  NEALE Australian      Med.      Gaz., 

1893,  xii. 

3.  SCHLAGER    ...  In.  Dis.,  Gottingen,  1874. 

4.  MOSLER     .   .  .   .  D.  M.  W.,  1872,  x.  160. 

5.  KELLER     .  .  .  .  W.  M.  W.,  1872,  xxii. 

6.  LORINSER     .   .   .  W.  M.  W.,  xix.,  xx. 

7.  HALLER    .  .  .   .  W.  M.  W.,  xxvi. 

8.  BOHN B.  K.  W.,  1872. 

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1872. 

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1870,  xix. 

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12.  BRUDELL  .  .  .  .  B.  G.  T.,  May,  1875. 

13.  SEITZ Bayer.  Aerztl.  Intell.  Blatt., 

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15.  FAULDS G.  M.  J.,  1902. 


FAMILY  V.— ANTIPYRETICS. 


UNDER  the  term  Antipyretics  are  to  be  considered  certain  remedies 
which  are  used  in  practical  medicine  for  the  purpose  of  reducing  bodily 
temperature  in  fever.  Most  of  these  remedies  conjoin  to  their  antipy- 
retic properties  the  capability  of  relieving  pain  which  is  not  due  to  inflam- 
matory or  other  distinctly  local  diseases  or  traumatism.  Some  of  them  are 
actively  antirheumatic.  The  different  members  of  the  class  vary  greatly 
in  the  activity  of  what  may  be  termed  their  secondary  properties,  some  of 
them  being  used  in  reality  almost  entirely  as  antirheumatics  or  analgesics, 
their  antipyretic  powers  being  inferior  for  practical  purposes  to  those  of 
other  members  of  the  group. 

The  method  in  which  antipyretics  reduce  fever  temperature  has  not 
been  thoroughly  worked  out,  but  it  is  probable  that  they  exert  their  in- 
fluence by  an  action  upon  the  thermogenetic  or  thermo-inhibitory  centres. 
On  the  other  hand,  it  is  possible  that  they  have  such  immediate  influence 
on  the  chemical  processes  in  the  various  tissues  of  the  body  as  to  directly 
affect  the  production  of  heat. 

The  question  as  to  whether  it  is  better  in  fever  to  reduce  the  excessive 
temperature  by  the  administration  of  an  antipyretic,  or  by  the  use  of  the 
cold  bath,  is  one  to  which  at  present  a  positive  answer  cannot  be  given. 
So  far  as  our  present  knowledge  goes  the  antipyretics  produce  greater 
disturbances  in  the  general  functions  of  the  body  than  is  caused  by 
what  we  may  call  the  mechanical  abstraction  of  heat.  Further,  the 
fever  process  itself  is  a  disturbed  condition  of  the  nutrition,  which  is  by 
no  means  thoroughly  comprehended.  In  the  administration  of  an  anti- 
pyretic we  are  attempting  to  modify  for  the  better  a  morbid  process  of 
whose  real  nature  we  are  ignorant  by  the  use  of  a  powerful  drug  of  whose 
action  we  have  not  definite  knowledge.  The  use  of  the  antipyretics  is  at 
present  empiric,  and  in  our  lack  of  knowledge  the  cold  bath  would  seem 
to  be  a  safer  remedy  than  the  drug.  The  greater  convenience  of  anti- 
pyretics, however,  exerts  a  constant  pressure  for  their  use  by  the  physi- 
cian, and  little  by  little  confidence  in  them  seems  to  be  growing.  Our 
own  belief  is  that  in  minor  cases  of  fever  the  antipyretic  is  often  superior 
to  the  cold  bath  because  of  its  greater  ease  of  application,  but  that  in 
the  severe  cases  of  fever,  especially  when  there  is  a  tendency  to  persistent 
adynamia,  the  best  results  are  to  be  achieved  by  relegating  antipyretics 
to  the  class  of  adjuvants,  employing  them  in  moderate  dose  simply  for 
the  purpose  of  assisting  the  cold  bath,  and  of  prolonging  its  influence. 
586 


ANTIPYRETICS.  587 

ACIDUM  SALICYLICUM— SALICYLIC  ACID.     U.  S. 

Salicylic  acid  occurs  in  long  acicular  crystals  or  in  the  form  of  a  white, 
dull  powder,  of  a  peculiar  pungent  odor,  and  a  mild,  peculiar  taste, 
accompanied  by  a  transient  sense  of  numbness.  It  is  soluble  at  25°C  ., 
in  about  three  hundred  and  seven  parts  of  water  and  in  2.1  parts  of 
alcohol. 

PHYSIOLOGICAL  ACTION.—  Local  Action.— Absorption  and  Elimina- 
tion.— Pure  salicylic  acid  is  so  actively  irritant  to  mucous  membranes  that 
its  less  irritant  compounds  are  universally  preferred  in  practical  medicine. 
It  is  absorbed  rapidly  through  mucous  membranes,  and  also  to  a  less  ex- 
tent through  the  skin  when  applied  in  alcoholic  solution  (Drasche1),  or  in 
the  form  of  a  soluble  compound.  It  circulates  as  a  sodium  or  other  sali- 
cylate.  Many  of  its  insoluble  compounds,  such  as  strontium  salicylate, 
bismuth  salicylate,  etc.,  undergo  slow  decomposition  in  the  alimentary 
canal,  yielding  their  salicylic  acid  to  the  alkaline  intestinal  juices,  and 
subsequent  absorption. 

Salkowski  *  pointed  out  that  salicylic  acid  in  the  blood  probably  exists  in  the 
form  of  the  sodium  salt.  Binz s  supposes  that  the  acid  is  liberated  in  the  blood  by 
the  carbonic  acid  formed  in  the  tissues.  The  only  basis  for  this  theory  consists  in 
the  fact  that  by  passing  carbonic  acid  gas  through  a  solution  of  sodium  phosphate, 
carbonate,  and  salicylate,  agitating  with  ether,  and  separating  and  evaporating  the 
latter,  crystals  of  salicylic  acid  are  obtained.  It  is  evident  that  if  in  the  blood  changes 
take  place  similar  to  those  which  occur  in  this  solution,  salicylic  acid  should  be 
yielded  to  ether  shaken  with  the  blood  of  an  animal  poisoned  with  the  drug.  Feser 
and  Friedeberger  found  that  unless  enormous  doses  of  the  drug  were  injected  into 
the  blood  so  as  to  produce  immediate  violent  convulsions  and  death,  the  vital  fluid  of 
the  poisoned  animal  yielded  nothing  to  ether.  In  Kohler's4  experiments,  when 
salicylic  acid  was  dissolved  in  normal  blood  no  acid  was  yielded  to  ether  ;  but  when 
the  blood  of  asphyxia — i.  <?.,  blood  supersaturated  with  carbonic  acid — was  em- 
ployed, a  very  notable  amount  of  the  acid  was  extracted  by  the  ether.  These  ex- 
periments warrant  the  conclusion  that  when  the  blood  is  in  the  normal  condition 
the  alkaline  salicylates  are  not  decomposed  by  the  carbonic  acid  in  it. 

Feser  and  Friedeberger  have  advanced  the  theory  that  the  salicylic  acid  circu- 
lates in  the  form  of  an  albuminate.  This  has  received  some  support  from  the 
experiments  of  Farsky,5  which  seem  to  show  that  the  acid  is  capable  of  forming 
such  a  compound.*  On  the  other  hand,  the  theory  is  contradicted  by  the  results 
of  Fleischer,6  who  digested  albuminous  solutions  with  the  acid,  and  after  coagula- 
tion by  heat  found  all  the  acid  in  the  nitrate,  and  who  also  treated  the  blood  of 
poisoned  animals  in  a  similar  way,  and  found  the  salicylic  acid  only  in  the  serum, 
the  coagulum  being  free. 

Salicylic  acid,  although  it  probably  enters  into  every  liquid  of  the 
organism,  escapes  from  the  body  chiefly  through  the  kidneys,  f  its  elimi- 

*  He  digested  various  albuminous  substances  with  salicylic  acid,  washed  them  with 
ether  until  it  would  take  no  more  acid,  dried,  washed  with  water,  and  found  on  analysis 
salicylic  acid  largely  present  in  the  residue. 

t  To  detect  salicylic  acid  in  the  urine,  add  the  solution  of  chloride  of  iron  carefully. 
At  first  white  phosphate  of  iron  precipitates,  then,  if  the  acid  be  present,  a  violet  color  is 
produced  (Kolbe). 


588  GENERAL   REMEDIES. 

nation  beginning  almost  immediately  after  its  ingestion.  It  appears  to  be 
excreted  partly  as  salicylic  acid  and  as  a  salicylate,  partly  as  salicyluric 
acid,  and  partly  as,  at  present,  unknown  educts. 

Ugolino  Mosso '  recovered  from  the  urine,  both  in  man  and  animals,  practically 
all  of  the  salicylic  acid  which  had  been  ingested,  either  in  the  form  of  salicylic  or 
salicyluric  acid.  Fiirbringer  and  Drasche  failed  to  detect  it  in  the  faeces,  the 
saliva,  the  bronchial  secretion,  or  the  sweat,  but  Mussy 8  found  it  in  the  saliva,  as 
did  also  Balz,  and  Oulmont  detected  it  in  the  serosity  of  a  blister.  It  appears  in 
the  urine  very  soon  after  its  ingestion,  but  its  elimination  proceeds  slowly.  Thus,  in 
a  case  of  exstrophy  of  the  bladder  it  was  detected  in  the  urine  dripping  from  the 
ureter  eight  and  a  half  minutes  after  its  ingestion  (Balz9),  and  it  has  been  found 
in  the  urine  eight  days  after  the  exhibition  of  the  last  dose  (Byanow10).  The  latter 
observer  also  found  it  in  the  urine  of  a  normal  man  as  a  salicylate  twenty-five  min- 
utes after  its  swallowing.  The  same  authority  states  that  it  is  excreted  partly  as 
salicyluric  acid,*  partly  as  a  form  of  salicin,  and,  he  believes,  to  some  extent  as 
oxalic  acid.  Urine  which  had  been  passed  some  hours  after  the  ingestion  of  a  dose 
polarized  to  the  left.  A.  E.  Stuart,11  after  so  small  a  dose  as  nine  grains  of  the  acid, 
saw  free,  distinct  crystals  of  salicyluric  acid  in  the  urine.  It  is  possible  that  such  of 
the  salicylic  acid  as  escapes  unchanged  from  the  kidney  may,  as  first  excreted,  be 
in  the  form  of  a  salicylate,  but  be  set  free  by  the  phosphoric  acid  of  the  urine  ;  at 
least  such  would  be  indicated  by  the  fact  that  in  Balz's  case  of  exstrophy  sodium 
salicylate  appeared  in  the  urine  twelve  minutes  before  the  free  acid.  The  green 
color  of  the  urine  characteristic  of  the  free  use  of  salicylic  acid  appears  to  be  due  to 
an  increase  in  the  formation  of  indican  (S.  Wolfberg,12  M.  Robin13  ),  or  else  to  pyro- 
catechin  (Se'e14),  and  it  is  not  improbable  that  the  pyrocatechin  is  formed  out  of 
the  salicylic  acid. 

General  Effects. — When  salicylic  acid  is  given  to  man  in  doses  just 
sufficient  to  manifest  its  presence,  symptoms  closely  resembling  cin- 
chonism  result.  These  are  fulness  of  the  head,  with  roaring  and  buzzing 
in  the  ears.  After  larger  doses,  to  these  symptoms  are  added  distress  in 
the  head,  or  positive  headache,  disturbances  of  hearing  and  vision  (deaf- 
ness, amblyopia,  partial  blindness),  and  excessive  sweating.  According 
to  Reiss,15  decided  fall  of  temperature  without  alteration  of  the  pulse 
also  occurs  ;  but  this  is  denied  by  other  observers. 

The  urine  may  be  increased,  diminished,  or  in  normal  amount  during 
the  administration  of  salicylic  acid.  After  toxic  doses  it  becomes  albu- 
minous, and  Se'e  reports  a  case  in  which  the  renal  irritation  was  so  severe 
as  to  give  rise  to  hsematuria. 

In  salicylic  acid  poisoning,  along  with  an  intensification  of  the  symp- 
toms already  mentioned,  there  are  ptosis,  deafness,  strabismus,  mydriasis, 
disturbance  of  respiration,  excessive  restlessness  passing  into  delirium, 
slow  laboring  pulse,  leucocytosis,  olive-green  urine,  and  involuntary 
evacuations.  In  some  cases  the  temperature  has  remained  about  normal, 
but  in  others  has  approached  that  of  collapse.  The  respiration  appears 
to  be  almost  characteristic  :  it  is  both  quickened  and  deepened.  In  some 

*  Salicyluric  acid  is  a  parallel  compound  to  hippuric  acid,  made  by  the  union  of  the 
elements  of  glycocoll  with  salicylic  acid. 


ANTIPYRETICS.  589 

cases  the  dyspnoea  has  been  extreme,  and  given  rise  to  the  most  violent 
respiratory  efforts.  Various  local  evidences  of  vaso-motor  weakness 
may  supervene,  such  as  rapidly  appearing  bed-sores  at  points  subjected 
to  pressure,  and  transitory  dark-colored  maculae  on  various  parts  of  the 
body.* 

In  several  cases  death  has  probably  been  produced  by  the  acid.  The  most  con- 
clusive case  is  that  of  H.  Quincke.16  The  chief  post-mortem  changes  were  a 
breaking  down  of  the  blood,  congestion  of  most  of  the  viscera,  and  ecchymoses  in 
the  serous  membranes,  f 

In  rare  instances  even  the  therapeutic  use  of  salicylic  acid  has  pro- 
duced severe  skin  eruptions.  The  form  has  been  sometimes  like  that  of 
urticaria,  in  other  cases  it  has  been  exanthematous,  bullatous,  or  even 
purpuric  and  gangrenous.  £ 

In  some  cases  of  salicylic  acid  poisoning  the  mental  disturbance  has 
been  prolonged  a  week  or  more.  It  is  stated  that  upon  drunkards 
the  acid  acts  very  unfavorably,  violent  delirium  being  a  common  and 
early  symptom  of  its  influence.  There  are  also  some  persons  whose 
idiosyncrasies  are  such  that  mental  disturbance  is  produced  even  by  mod- 
erate doses  of  the  acid.  In  some  cases  the  delirium  is  cheerful,  in  others 
it  is  melancholic  in  type.  In  the  mildest  form  it  is  manifested  only  by  a 
tendency  to  dream  actively  and  to  talk  during  sleep.  In  other  cases  the 
roaring  in  the  ears  soon  becomes  associated  with  disturbances  of  vision, 
which  grow  more  marked  until  the  patient  not  only  sees  objects  in  false 
appearances  and  colors  but  has  absolute  illusions.  The  hallucinations 
are  apt  to  take  the  shapes  of  animals  such  as  are  seen  in  delirium  tremens, 
but  there  is  usually  little  or  no  terror,  and  the  troops  of  images  may 

*  For  cases,  consult  Deutsches  Archiv  f.  Klin.  Med.,  xix.  319;  Centralbl.f.Chirur- 
gie,  1877,  278, — four  hundred  and  one  grains  of  sodium  salicylate  taken  in  twelve  hours ; 
London  Lancet,  1876,  2,  681 ;  Berlin  Klin.  Wochenschrift ,  1876,  No.  4,  8 ;  and  Bull. 
Thtrap.,  1877,  xciii.  25. 

t  In  the  case  recorded  in  the  Virginia  Med.  Monthly,  June,  1877,  forty-eight  grains  of 
the  acid  were  taken  in  four  hours.  The  symptoms  were  violent  vomiting,  headache,  total 
unconsciousness,  and  stertorous  breathing.  Death  occurred  forty  hours  after  the  first 
dose.  Our  belief  is  that  either  much  more  of  the  acid  than  forty-eight  grains  was  taken, 
or,  what  is  more  probable,  death  was  from  some  other  cause.  (See  also  Med.  and  Surg. 
Reporter,  1878.)  There  is  no  probability  that  in  the  alleged  case  of  poisoning  reported  by 
Frank  Ogston  (Brit.  Med.  Journ.,  1883,  i.  869)  the  salicylate  had  anything  to  do  with  the 
untoward  symptoms  or  result.  The  case  reported  by  Dixneuf  (  These,  Paris,  1878),  also 
that  of  Empis  and  Gubler  (Bull,  de  I'Acad.  Med.  1877),  we  have  not  had  opportunity  to 
examine.  It  is  worthy  of  remark  that  in  the  early  history  of  the  use  of  the  salicylates 
disagreeable  symptoms  appear  to  have  been  present  much  more  frequently  than  of  later 
years,  and  it  is  very  probable  that  m  many  cases  such  symptoms  have  been  due  to  the 
presence  of  impurities.  Thus,  paracresotic  acid  has  been  isolated  from  commercial 
salicylic  acid  by  Dunstan.  Both  it  and  orthocresotic  acid  have  been  found  by  Charteris 
to  be  very  fatal  poisons  to  the  lower  animals,  producing  general  paralysis  and  death  from 
asphyxia.  One  grain  of  orthocresotic  acid  and  two  grains  of  paracresotic  acid  caused 
death  in  three  hours  in  rabbits  weighing  two  pounds  (Brit.  Med.  Journ.,  1891,  i.)- 

%  Journ.  of  Cutaneous  and  Genito-Urin.  Diseases,  1896 ;  see  especially  Deutsch.  Med. 
Wochenschr.,  1886. 


59o  GENERAL  REMEDIES. 

march  to  beautiful  music.  In  other  cases  the  delirium  amounts  to  acute 
mania,  with  restlessness,  violent  outcries,  and  even  a  fury  of  righting 
(J.  Krueg17).  Mydriasis  and  amblyopia  like  that  caused  by  quinine 
have  been  noticed  in  a  number  of  cases,  but  Gibson  and  Felkin 18  report 
excessive  myosis,  with  loss  of  the  light  reflexes. 

When  given  to  dogs  by  the  mouth  in  large  doses,  salicylic  acid  is  said  to  be 
usually  vomited.  According  to  Laborde,19  when  from  four  to  five  grammes  of 
sodium  salicylate  are  injected  into  the  veins  of  the  dog  the  first  result  is  a  slight 
acceleration  of  the  heart's  action  and  of  breathing ;  this  is  followed  by  efforts  at 
vomiting,  quietude,  loss  of  muscular  strength,  with  a  decidedly  ataxic  gait,  hebe- 
tude, stupor,  dyspnoea,  general  convulsions,  and  death  from  asphyxia. 

Nervous  System. — So  far  as  we  know,  the  single,  even  large,  thera- 
peutic dose  of  salicylic  acid  has  no  distinct  action  upon  the  nervous 
system,  unless  it  be  upon  the  peripheral  ends  of  the  auditory  and  perhaps 
other  nerves  of  special  sense,  the  tinnitus  aurium  caused  by  it  indicating 
that  upon  these  organs  it  acts  as  does  quinine.  The  symptoms  of  salicylic- 
acid  poisoning  indicate  that  the  drug  does  act,  when  in  overwhelming 
dose,  upon  the  cerebral  cortex  ;  how  far  other  portions  of  the  nervous 
system  are  affected  is  at  present  uncertain.  It  is  probable  that  the  feeling 
of  depression  often  produced  by  the  free  continuous  use  of  the  salicylates 
is  largely  the  outcome  of  an  influence  upon  the  cerebral  cortex. 

According  to  S^e,  neither  the  reflexes  nor  the  general  sensibility,  nor  the  con- 
ducting power  of  the  nerve-trunks  are  sensibly  impaired  in  the  lower  animals  poi- 
soned by  a  salicylate,  but  Laborde  states  that  a  drachm  of  the  salicylate  will 
produce  in  a  dog  profound  cutaneous  anaesthesia  ;  and  Bochefontaine  affirms  that  in 
the  frog  the  drug  depresses  the  spinal  cord,  it  may  be  to  the  point  of  paralysis. 

Respiration. — The  respiratory  phenomena  produced  by  salicylates  in 
the  lower  animals  are  said  to  be  quickening,  followed  by  slowing,  of  the 
respiration,  with  gradual  failure  until  death  from  asphyxia  results.  The 
slowing  and  final  paralysis  are  probably  due  to  a  direct  action  upon  the 
respiratory  centre.  The  primary  quickening  has  been  ascribed  with  plausi- 
bility to  irritation  of  the  pulmonary  vagi,  though  it  is  probable  that  there 
is  primary  stimulation  of  the  respiratory  centre. 

When,  in  Kohler's  experiments,  the  pneumogastrics  were  divided  during  the 
period  of  retardation,  the  frequency  of  the  respiration  was  still  further  lessened. 
Danewsky  M  practised  section  of  the  vagi  before  exhibiting  the  drug  and  during  the 
first  stage  of  accelerated  breathing.  In  the  first  instance  he  found  that  the  breathing 
was  only  slightly  accelerated  by  the  drug  ;  in  the  second,  that  the  quickened  respi- 
ration fell  to  the  same  slowness  that  is  seen  in  the  unpoisoned  animal  with  cut 
pneumogastrics.  His  experiments  were  too  few  to  be  conclusive,  but  indicate  the 
correctness  of  his  deduction. 

Muscles. — According  to  Charles  Livon,21  salicylic  acid  has  a  distinct 
influence  upon  the  muscle-tissue  of  the  frog,  producing  a  primary  in- 


ANTIPYRETICS.  591 

crease  and  secondary  decrease  of  excitability  and  altering  the  character 
of  the  muscular  contractions. 

Circulation. — There  was  at  one  time  a  belief  not  only  among  clinicians, 
but  also  physiologists,  that  salicylic  acid  even  in  small  doses  decreases  the 
arterial  pressure.  It  seems,  however,  to  be  established  that  whilst  toxic 
doses  of  salicylic  acid  do  depress  arterial  pressure,  moderate  doses  exert 
no  such  influence  ;  indeed,  Danewsky  is  probably  correct  in  asserting 
that  they  increase  the  arterial  pressure  by  stimulating  the  vaso-motor 
centres.  The  final  fall  of  the  arterial  pressure  is  in  large  part,  if  not 
altogether,  due  to  a  direct  action  of  the  drug  upon  the  heart  itself. 

E.  Maragliano,22  in  a  very  large  number  of  sphygmographic  and  sphygmomano- 
metrical  studies,  found  the  arterial  pressure  usually  elevated,  and  never  depressed, 
by  therapeutic  doses  of  the  drug.  In  1879  Hugues  Oltremare  23  affirmed  that  mod- 
erate doses  of  sodium  salicylate  increased  the  frequency  of  the  pulse  and  the  arte- 
rial pressure,  and  in  this  was  subsequently  confirmed  by  Danewsky.  According  to 
the  latter  observer,  although  the  force  and  energy  of  the  cardiac  beat  are  increased 
by  the  small  dose  of  the  drug,  yet  the  inability  of  the  salicylate  to  elevate  the  arte- 
rial pressure  after  section  of  the  spinal  cord  shows  that  the  main  factor  in  the  rise 
of  the  blood-pressure  is  spasm  of  the  blood-vessels  due  to  stimulation  of  the  vaso- 
motor  centres  in  the  medulla.  Kohler,  Oltremare,  and  Danewsky  have  found  that 
after  toxic  doses  the  arterial  pressure  steadily  falls,  the  heart-stroke  becoming 
weaker  and  weaker,  and  finally  being  extinguished.  Kohler,  determining  that  the 
fall  of  pressure  is  not  prevented  by  previous  section  of  the  depressors,  the  vagi, 
and  the  cervical  cord,  logically  concludes  that  it  is  due  to  an  action  upon  the  heart 
itself.  In  Paul  Faval's 2*  experiments  upon  the  isolated  heart  of  the  frog,  small  doses 
of  salicylic  acid  had  no  perceptible  influence,  although  large  doses  paralyzed  the 
viscus.  W.  Wiechowski,5*  as  the  result  of  an  elaborate  research,  believes  that  sali- 
cylic acid  acts  specifically  upon  the  brain  circulation  in  causing  contraction  of  the 
blood-vessels,  but  that  this  action  is  not  shared  by  benzoic  acid,  by  aspirin,  or  by 
the  oil  of  gaultheria.  He  quotes  as  concurrent  with  his  conclusion  the  observations 
of  Uhthoff,  that  salicylic  acid  produces  narrowing  of  the  retinal  vessels. 

Digestive  Tract. — The  indigestion,  loss  of  appetite,  and  nausea  which 
often  interfere  with  the  usefulness  of  salicylic  acid  and  its  compounds  are 
not  due  to  the  irritant  action  of  the  drug  so  much  as  to  an  influence  of 
the  salicylate  on  the  action  of  the  digestive  ferments  ;  even  when  the  sali- 
cylates  are  not  administered  during  digestion,  it  is  probable  that  they  are 
excreted  continuously  into  the  stomach  and  exert  their  specific  action. 

According  to  Kolbe  and  others,  salicylic  acid  arrests  or  prevents  the  action  of 
the  non-organized  organic  ferments.  Thus,  it  will  inhibit  the  action  of  emulsin 
upon  amygdalin  or  upon  myronic  acid,  and  prevent  the  development  of  hydrocyanic 
acid  or  of  the  volatile  oil  of  mustard.  Miller  found  that  one  per  cent,  of  salicylic 
acid  was  sufficient  to  check  the  action  of  ptyalin  upon  starch  ;  for  the  same  effect 
ten  per  cent,  of  carbolic  acid  was  required.  The  digestive  action  of  pepsin,  outside 
of  the  body,  was  very  seriously  affected  by  0.2  per  cent,  of  salicylic  acid  in  Miller's 
studies,  but  in  Kolbe' s  experiments  the  ingestion  of  twenty  grains  a  day  of  the  drug 
had  no  demonstrable  effect. 

The  belief  of  many  clinicians  that  the  salicylates  have  a  distinct  action 
in  stimulating  biliary  secretion  seems  to  have  a  solid  experimental  foun- 


592  GENERAL  REMEDIES. 

dation  in  the  researches  of  H.  Moreigne,5i  in  the  experiments  made  upon 
animals  by  various  observers,  and  in  the  observations  of  William  Bain  and 
of  Pfaff  and  Balch  upon  human  beings  suffering  from  biliary  fistula.  (See 
PURGATIVES.  ) 

Nutrition. — The  experiments  of  Haig,25  of  S.  Wolfsohn,26  of  C.  Vir- 
chow,"  of  E.  G.  Salome,23  of  M.  Kumagawa,29  of  F.  Tausk  and  B.  Vas,M 
of  Bohland,51  and  of  F.  G.  Goodbody,5*  which  have  been  made  upon 
various  animals  and  upon  healthy  men  are  so  numerous  and  concordant 
in  their  relations  as  to  prove  that  in  the  normal  man  or  animal  salicylic 
acid  and  its  preparations  increase  to  a  very  great  extent  the  elimination  of 
urea  and  uric  acid.  In  the  experiments  of  Kumagawa,  the  uric  acid  was 
increased  in  the  healthy  dog  from  thirty  to  seventy-four  per  cent.  There 
was  also  marked  increase  in  the  elimination  of  sulphur  compounds, 
although  the  relation  between  the  elimination  of  nitrogen  and  sulphur, 
which  in  the  normal  animal  is  fixed,  was  distinctly  disturbed. 

The  question  whether  the  increased  elimination  of  urea  and  uric  acid, 
produced  by  the  salicylic  acid,  is  due  to  an  increased  formation  of  these 
substances,  or  is  simply  the  outcome  of  increased  activity  in  elimination, 
cannot  at  present  be  answered  positively.  Schreiber  and  Zandy 32  would 
seem  to  be  correct  in  believing  that  there  is  increased  formation  of  urea, 
but  the  experiments  of  Lecorch£  and  Salamon  indicate  that  in  rheumatism 
the  action  of  the  acid  is  rather  in  favoring  elimination  than  increasing  for- 
mation. Thus,  these  observers  found  that  in  acute  rheumatism  there  is 
under  the  influence  of  salicylates  an  increase  both  of  urea  and  uric  acid, 
usually  lasting  three  or  four  days,  and  then  followed  by  a  lessening  of  the 
excretion,  which  in  many  cases  carries  the  elimination  of  these  substances 
below  the  normal.  If  the  theqry  of  increased  formation  of  urea  and  uric 
acid  under  the  influence  of  salicylic  acid  be  adopted,  the  question  naturally 
arises  as  to  the  method  in  which  the  drug  acts  in  producing  the  increased 
formation.  Concerning  this  we  have  no  light  at  all. 

Closely  connected  with  the  subject  of  the  action  of  the  salicylates  upon 
nutrition  is  that  of  their  influence  upon  temperature.  Both  in  the  normal 
man  and  in  the  lower  animals,  except  in  rare  cases,  even  the  largest 
therapeutic  doses  of  the  salicylates  do  not  lower  the  bodily  temperature 
(Furbringer,M  Gedl,"  Danewsky,  and  Se"e).  It  is  probable,  however, 
that  salicylic  acid,  like  quinine,  has,  in  non-toxic  doses,  some  control  over 
thermogenesis  in  health.  Thus,  in  one  or  two  experiments  upon  him- 
self, North 35  found  that  the  acid  exerted  a  decided  influence  in  preventing 
*he  rise  of  bodily  temperature  normally  caused  by  exercise. 

In  fever  the  antipyretic  action  of  the  salicylates  is  very  pronounced  ; 
usually  in  about  fifteen  minutes  after  the  administration  of  the  drug  a 
profuse  sweat  appears,  which  is  soon  followed  by  a  fall  of  temperature 
that,  according  to  Justi,16  reaches  its  maximum  in  about  six  hours.* 

*  The  statements  in  regard  to  the  action  of  salicylic  acid  on  the  pulse  in  fever  vary 
so  much  as  to  suggest  that  when  any  decided  lessening  of  the  cardiac  beat  does  occur,  it 
is  dependent  upon  the  fall  of  temperature.  Thus  Garcin  (Journ.  de  Therap.,  1876,  25), 


ANTIPYRETICS.  593 

The  sweating  is  profuse  and  exhausting,  amounting,  according  to  Ewald, ST  not 
rarely  to  seven  hundred  and  fifty  grammes.  The  perspiration  can  scarcely  be  the 
chief  factor  in  the  reduction  of  temperature,  as  there  appears  to  be  no  relation 
between  its  amount  and  the  degree  of  the  fall,  and  it  usually  ceases  before  the 
latter  reaches  its  maximum. 

In  what  way  the  fall  of  temperature  is  produced  we  have  at  present 
no  knowledge,  since  in  the  only  experiments  upon  the  subject — those  of 
Hobart  A.  Hare,*8 — the  doses  employed  were  not  sufficient  to  give  posi- 
tive results. 

Especially  was  this  true  in  the  experiments  made  upon  animals  suffering  from 
fever.  Indeed,  there  was  not  in  those  animals  any  fall  of  bodily  temperature  under 
the  influence  of  the  salicylic  acid  administered.  To  attempt  to  reason  from  the 
results  reached  as  to  the  method  of  the  action  of  salicylic  acid  when  it  does  cause 
fall  in  bodily  temperature  seems  futile. 

SUMMARY. — Salicylic  acid,  and  to  a  less  degree  the  salicylates,  are 
irritant  to  the  mucous  membranes,  though  it  is  probable  that  the  dis- 
order of  digestion  produced  by  the  acid  and  its  salts  is  chiefly  due  to 
their  inhibiting  the  activity  of  the  digestive  ferments.  Salicylic  acid 
is  readily  absorbed  and  probably  circulates  in  the  blood  as  a  sodium 
or  other  salicylate ;  it  is  eliminated  partly  unchanged  as  a  salicylate, 
partly  as  salicyluric  acid,  the  green  discoloration  of  the  urine  being 
due  to  indican,  or  perhaps  to  pyrocatechin,  -which  may  be  an  educt 
from  the  acid.  The  elimination  both  of  urea  and  uric  acid  is  increased 
by  the  salicylates.  It  is  probable  that  this  increase  is  due  to  some 
action  upon  general  protoplasmic  chemical  activities,  though  it  may 
be  that  the  salicylates  increase  chiefly  the  elimination  of  formed  urea 
and  uric  acid.  In  full  doses  salicylic  acid  causes  symptoms  resembling 
those  produced  by  quinine,  but  after  larger  doses  there  are  mydriasis, 
marked  disturbance  of  respiration,  great  nervous  prostration,  delirium, 
dyspnoea,  and,  if  the  dose  has  been  large  enough,  death  by  respiratory 
paralysis.  Moderate  therapeutic  doses  appear  to  have  no  powerful 
influence  upon  the  circulation,  such  physiological  evidence  as  -we  have 
indicating  that  they  increase  arterial  pressure  somewhat  by  exciting 
the  vaso-motor  centre  and  directly  increasing  the  cardiac  force.  In 
overdoses  salicylic  acid  causes  fall  of  the  arterial  pressure,  partly  by  a 
direct  action  upon  the  heart.  Our  knowledge  of  the  action  of  the  acid 
upon  the  nervous  system  is  very  imperfect,  but  it  seems  to  be  a  de- 
pressant of  the  motor  nervous  centres.  Moderate  doses  increase  the 
frequency  of  the  respiration,  probably  in  part  by  an  action  upon  the 
peripheral  pneumogastrics,  but  chiefly  by  a  direct  influence  upon  the 
respiratory  centre.  Toxic  doses  paralyze  the  respiratory  centre.  The 
action  of  salicylic  acid  upon  the  temperature  of  normal  man  is  slight 
and  inconstant,  unless  toxic  doses  be  given;  in  fever  its  antipyretic 
influence  is  pronounced,  but  we  have  no  exact  knowledge  as  to  the 
method. 

THERAPEUTICS. — The  salicylates  were  originally  introduced  by  E. 
Butt39  for  the  purpose  of  reducing  temperature  in  typhoid  and  other 

Oulmont  (Le  Progrts  Mtd.,  1877,  587),  and  Moeli  (Deulsches  Archiv,  xvii.  592)  have 
all  observed  the  pulse-rate  to  fall  with  the  fever-heat,  while  L.  Schroeder  affirms  that 
after  moderate  doses  the  pulse  is  slackened,  after  large  ones  quickened,  and  Ewald  and 
other  observers  state  that  it  is  usually  not  affected. 

38 


594  GENERAL    REMEDIES. 

fevers,  but  have  been  superseded  by  various  agents  which  are  not  only 
more  effective  but  more  sure  and  less  disagreeable  in  their  action.  In 
1876  Strieker,40  of  Berlin,  using  salicylic  acid  as  an  antipyretic  in  acute 
rheumatism,  discovered  the  extraordinary  antirheumatic  influence  of 
the  salicylates,  which  have  come  to  be  the  standard  remedy  in  all 
forms  of  rheumatism.  Of  all  known  agents  the  salicylates  are  possessed 
of  the  most  power  for  good  in  acute  inflammatory  rheumatism,  in 
subacute  or  muscular  rheumatism,  in  rheumatic  neuritis  and  other  ir- 
regular forms  of  rheumatism,  and  are  often  temporarily  of  great  service 
even  in  chronic  rheumatism.  In  gout  the  powers  of  the  salicylates  for 
good  are  much  less  than  they  are  in  rheumatic  diseases,  but  in  all  of 
the  irregular  forms  of  gouty  diseases  a  salicylate  should  be  tried,  and 
will  often  be  found  to  be  of  temporary  service  ;  they  usually  combine 
well  with  colchicum.  Clinical  experience  has  demonstrated  that  in 
these  various  conditions  the  salicylates  seem  to  be  palliative  rather 
than  curative  ;  in  other  words,  that  they  for  the  present  modify  and 
overcome  the  rheumatic  symptoms,  but  that  they  exert  no  permanent 
influence  upon  the  diathesis  which  is  the  basis  of  the  disease.  In  septic 
simulations  of  rheumatism,  such  as  gonorrhceal  rheumatism,  and  in 
rheumatoid  arthritis,  the  salicylates  are  rarely  of  any  service.  In  rheu- 
matic angina  and  in  quinsy,  which  seems  to  have  some  relation  to  the 
rheumatic  diathesis,  the  salicylates  often  do  good  ;  they  are,  however,  of 
no  value  in  diphtheria.  At  one  time  the  salicylates  were  used  to  a  con- 
siderable extent  in  chronic  cystitis  and  chronic  pyelitis  for  their  influence 
upon  the  inflamed  mucous  membrane,  but  at  present  are  rarely  employed. 

The  salicylates  have  been  used  to  some  extent  as  antiperiodics,  but 
the  general  drift  of  experience  coincides  with  that  of  Helley,  who  found 
salicylic  acid  to  fail  in  severe  cases  of  malaria,  and  to  require  a  longer 
time  for  the  cure  of  mild  cases  than  does  quinine. 

As  alterative  diuretics  the  salicylates  have  been  commended  by 
Armin  Huber41  and  other  clinicians42  in  the  treatment  of  acute  and 
chronic  pleurisy  with  watery  effusions. 

Use  in  Diseases  of  the  Eye. — The  salicylates  are  of  the  greatest  value 
in  the  treatment  of  iritis,  iridocyclitis,  iridochoroiditis ,  and,  in  general 
terms,  in  uveitis.  They  relieve  the  pain  of  acute  and  sub-acute  glaucoma, 
and  even  cures  of  the  so-called  malignant  glaucoma  by  them  have  been 
reported  by  Harry  Friedenwald,  whilst  the  course  of  sympathetic  ophthal- 
mia is  favorably  influenced  by  them. 

Naturally  the  promptest  results  are  obtained  in  rheumatic  cases,  but  in 
inflammations  of  the  uveal  tract,  not  of  rheumatic  origin,  they  frequently 
relieve  pain  and  aid  in  the  bringing  about  of  the  subsidence  of  the  inflam- 
mation. They  are  also  effective  in  certain  types  of  interstitial  and  other 
forms  of  keratitis,  in  herpes  of  the  cornea,  and  in  traumatisms  of  the  eyeball, 
associated  with  congestion  or  inflammation  of  the  iris  and  ciliary  bodies. 

In  order  to  get  the  proper  results  from  the  salicylates  in  diseases  of  the 
eye  it  is  essential  that  they  be  used  in  sufficient  dose.  Gifford  "  believes 


ANTIPYRETICS. 


595 


that  most  patients  are  able  to  take  daily  one  grain  of  sodium  salicylate  for 
each  pound  of  weight,  without  inconvenience.  Thus,  a  man  weighing 
150  pounds  should  tolerate  ten  fifteen-grain  doses,  given  one  and  a  half 
hours  apart. 

From  a  very  large  experience  I  am  sure  of  the  value  of  the  salicylates 
in  these  diseases  of  the  eye,  but  I  have  not  found  it  ordinarily  necessary 
to  use  the  massive  doses  advocated  by  Gifford.  His  plan  is  to  give  during 
the  first  twenty-four  hours  eighty  to  one  hundred  grains  ;  sixty  grains 
during  the  next  twenty-four  hours,  and  then  gradually  decrease  the  dose, 
administering  with  the  salicylates  small  doses  of  brandy  if  depression  be 
feared.  In  my  own  opinion  such  doses  should  be  reserved  for  the  serious 
types  of  ocular  inflammations,  especially  sympathetic  ophthalmia,  acute 
glaucoma,  and  iridocyclitis.  In  all  cases  the  local  treatment  of  the 
disease  must  not  be  neglected. 

Attempts  have  been  made  to  administer  the  drug  subconjunctivalry, 
but  both  in  man  and  in  rabbits  such  use  is  apt  to  produce  local  necrosis, 
and  in  the  writer's  experiments  upon  animals  there  has  been  caused  a 
degree  of  local  irritation  which  has  made  him  unwilling  to  make  trial  of 
the  method  upon  human  beings.  The  experiments  of  Fromaget  and 
Laffay K  indicate  that  the  solution  for  subconjunctival  medication  should 
never  be  stronger  than  five  per  cent.  So  far  as  I  am  aware  intravitreous 
injections  of  sodium  salicylate  have  not  been  practised  on  human  beings; 
although  the  experiments  of  Schoeler  show  that  in  the  rabbits  they  have 
the  power  to  check  metastatic  iridocyclitis. 

The  studies  of  Harold  Gifford  to  determine  the  manner  in  which  the 
salicylates  act  in  diseases  of  the  eye  have  not  led  to  definite  result.  As 
Gifford  points  out,  in  order  for  the  sodium  salicylate  to  check  the  growth 
of  the  ordinary  white  and  yellow  pus  cocci  it  requires  a  solution  of  from 
i  :iooo  to  i  :5oo,  so  that  the  bactericidal  influence  of  the  drug  can  scarcely 
be  a  potent  factor  in  its  action.  It  has  been  suggested  that  the  salicylate 
may  cause  a  local  depletion  in  the  inflamed  area,  the  arterioles  of  which 
have  been  dilated  ad  maximum  by  the  bacterial  toxins  by  producing  a 
general  capillary  dilatation.  Also,  that  the  diaphoresis  caused  by  the 
drug  is  an  important  factor  in  its  efficiency  ;  but  it  must  be  remembered 
that  other  drugs  which  produce  capillary  dilatation  and  free  sweating  are 
of  little  value  in  ocular  inflammation.* 

Use  as  an  Antiseptic. — Salicylic  acid  was  originally  brought  to  the 
notice  of  the  profession  on  account  of  its  inhibitory  influence  on  putre- 
faction. Kolbe 4S  found  that  o.  04  per  cent,  had  great  influence  in  prevent- 
ing souring  of  milk.  Buchholz  states  that  0.15  per  cent,  is  sufficient  to 
prevent  the  development  of  bacteria  in  ordinary  organic  mixtures,  and 
that  the  influence  of  0.005  Per  cent-  *s  plainly  visible  ;  0.3  to  0.4  per 
cent,  of  the  acid  killed  bacteria  in  vigorous  growth.  The  sodium  salicyl- 
ate was  about  equal  to  the  pure  acid,  0.4  per  cent,  destroying  the  bacteria. 

*  Written  by  Professor  George  E.  de  Schweinitz. 


596  GENERAL  REMEDIES. 

In  the  preservation  of  urine,  Meyer  and  Kolbe u  found  that  one  part  of 
salicylic  acid  to  two  thousand  parts  of  urine  was  sufficient  to  prevent 
putrefaction. 

Salicylic  acid  has  been  used  to  a  considerable  extent  in  the  prepara- 
tion of  beer  and  wine,  and  for  the  preservation  of  various  articles  of  food. 
On  February  7,  1881,  the  French  government  interdicted  this  use,  and 
in  1885  a  commission45  appointed  by  the  Academy  of  Medicine  of  Paris, 
at  the  suggestion  of  the  Minister  of  Agriculture,  reported  that  it  is  proved 
that  the  prolonged  employment  of  even  very  small  amounts  of  salicylic 
acid  is  dangerous,  and  that  in  susceptible  individuals,  and  especially  in 
aged  persons,  it"  is  apt  to  cause  disorder  of  digestion  and  renal  disease. 

There  can  be  no  doubt  that  salicylic  acid  is  capable  of  accomplishing 
much  in  antiseptic  surgery,  but  it  is  at  present  rarely  used. 

Locally,  salicylic  acid  is  a  distinct  irritant.  In  the  experiments  of 
Hbdara  **  its  prolonged  contact  with  the  skin  caused  swelling  of  the  epi- 
dermis, followed  after  a  time  by  desquamation  or  exfoliation,  the  cast-off 
flakes  having  a  thickness  in  direct  proportion  to  the  strength  of  the 
preparation  used.  When  the  application  was  continued  for  some  days 
oedema  and  necrosis  of  the  epithelium  resulted.  It  is  also  much  used  by 
dermatologists  in  various  skin  diseases  when  there  is  pronounced  thicken- 
ing of  the  epidermis. 

In  1875  Hirt  called  attention  to  the  irritation  of  the  pulmonic  mucous 
membrane  in  workmen  engaged  in  the  manufacture  of  salicylic  acid  ;  and 
various  specialists  have  employed  it  as  a  local  remedy  in  the  treatment  of 
chronic  laryngeal  and  pulmonic  inflammations. 

ADMINISTRATION. — The  salicylates  have  been  used  in  rheumatism 
according  to  two  methods.  By  one,  they  are  given  continuously  in 
moderate  dose  ;  by  the  other,  they  are  administered  in  very  large  dose 
up  to  the  production  of  cinchonism,  then  temporarily  withdrawn,  then 
readministered,  and  so  on  until  the  desired  effect  has  been  reached. 
When  the  symptoms  are  acute  the  alternative  method  of  administration  is 
better  than  the  attempt  to  make  the  continuous  prolonged  effect ;  and 
even  in  sub-acute  cases  of  the  disease  this  plan  of  medication  is  often 
singularly  effective. 

On  account  of  the  tendency  to  interfere  with  digestion  the  salicylates 
should  be  administered  about  two  hours  after  meals,  so  as  to  get  the 
minimum  gastric  effect  at  the  time  when  gastric  digestion  is  at  its  height. 
Owing  to  the  irritant  action  of  salicylic  acid  some  of  its  preparations  are 
at  present  always  preferred. 

Sodium  Salicylate  (Soon  SALICYLAS,  U.  S.)  is  a  freely  soluble  salt, 
very  unpleasant  to  the  taste,  but  efficient.  Ammonium  Salicylate 
(AMMONII  SALICYLAS,  U.  S. )  is  also  freely  soluble,  is  somewhat  less  un- 
pleasant to  the  taste  than  the  soda  salt,  and  for  most  purposes  is  preferable 
to  it.  Strontium  Salicylate  (STRONTII  SALICYLAS,  U.  S. )  slowly  yields 
its  salicylic  acid  in  the  alimentary  canal,  and  has  the  great  advantage  of 
being  much  less  likely  than  other  salicylates  to  derange  digestion.  It  is, 


ANTIPYRETICS.  597 

however,  too  slow  in  its  influence  to  be  used  when  a  quick,  powerful  effect 
of  the  salicylates  is  desired.  When  small  doses  only  are  to  be  employed, 
the  ammonium  salicylate  may  be  combined  with  the  strontium  salicylate 
in  capsules.  In  some  cases  five  grains  of  each  salt  thus  administered  are 
well  borne  by  the  stomach.  When,  however,  salicylates  are  to  be  em- 
ployed in  large  doses,  they  must  be  given  in  solution,  and  should,  unless 
under  very  exceptional  circumstances,  be  administered  in  milk.  When 
large  doses  of  the  salicylates  are  to  be  taken,  strychnine  and  often  tincture 
of  digitalis  may  be  given  with  them  to  overcome  their  depressing  effects. 
The  Oil  of  Gaultheria  is  as  prompt  in  its  influence  as  is  the  ammonium 
salicylate,  and  may  often  be  combined  with  it  or  used  by  itself. 

The  maximum  daily  dose  of  the  salicylates  may  be  set  down  as  one 
hundred  grains  (6.5  Gm.),  though  in  rare  cases  only  is  it  well  to  give 
over  seventy-five  grains,  and  usually  less  will  suffice.  In  subacute  cases 
thirty  grains  (2  Gm.)  is  an  average  dose.  The  occurrence  of  tinnitus 
aurium  is  an  evidence  of  systemic  intoxication,  and  should  be  the  signal 
for  the  lessening  of  the  dose. 

OLEUM  GAULTHERIA— OIL  OF  GAULTHERIA.  U.  S. 

Oil  of  gaultheria  is  a  very  volatile,  slightly  straw-colored  liquid,  of  a 
penetrating,  peculiar  odor,  ninety  per  cent,  of  which  is  methyl  salicylate. 
One  hundred  and  fifty-two  grains  of  methyl  salicylate  are  equivalent  to 
one  hundred  and  thirty-eight  grains  of  salicylic  acid. 

As  one  hundred  and  sixty-nine  grains  of  oil  of  gaultheria  contain  one 
hundred  and  fifty-two  grains  of  methyl  salicylate,  they  should  be  equiva- 
lent to  one  hundred  and  thirty-eight  grains  of  salicylic  acid. 

Oil  of  gaultheria,  Oil  of  Sweet  Birch  (OLEUM  BETUL.E,  U.  S. ),  and 
the  Methyl  Salicylate  prepared  synthetically  (METHYLIS  SALICYLAS, 
U.  S. )  are  so  similar  in  composition  that  they  probably  have  the  same 
action  upon  the  human  economy,  but  this  is  not  certain,  and  the  apoth- 
ecary should  always  put  up  the  exact  drug  prescribed. 

The  question  whether  the  natural  salicylic  acid  of  the  oil  of  gaultheria  has  any 
different  physiological  action  from  the  artificially  prepared  but  chemically  identical 
acid  has  been  elaborately  investigated  by  B.  J.  Stokvis,47  who  reaches  the  conclu- 
sion that  there  is  a  marked  quantitative  difference,  the  natural  acid  being  distinctly 
less  poisonous  than  the  artificial, — a  circumstance  which  he  believes  to  be  due  to 
the  superior  osmotic  properties  of  the  natural  acid,  causing  it  to  be  more  rapidly 
eliminated. 

Oil  of  gaultheria  is  more  irritant  than  the  other  salicylates,  but  is  ca- 
pable of  causing  all  the  ordinary  symptoms  of  salicylic  acid  poisoning. 

An  ounce  produced  violent  gastro-intestinal  irritation,  followed  by  convulsions, 
coma,  and  death  in  fifteen  hours,  Pinkham.48  In  Juvet's49  case  a  half-ounce  caused 
death;  but  the  same  amount  has  been  recovered  from  (Gallaher50),  probably  on 
account  of  the  vomiting  induced.  H.  C.  Wood  and  Hobart  A.  Hare51  have  shown 
that  the  physiological  action  of  gaultheria  is  the  same  as  that  of  salicylic  acid,  and 


593  GENERAL  REMEDIES. 

that  therapeutic  doses  are  entirely  decomposed  in  the  system,    although  toxic 
amounts  may  escape  in  part  unchanged. 

Oil  of  gaultheria  may  be  administered  in  emulsion  or  in  capsules  in 
doses  of  from  ten  to  fifteen  minims  (o.  6— i  C.c. ),  repeated  according  to 
circumstances.  We  have  given  as  high  as  one  hundred  and  fifty  drops 
of  it  in  twenty-four  hours,  though  few  persons  will  bear  more  than  half 
this  amount. 

Linossier  and  Lannois 52  found  that  salicylic  acid  could  be  detected  in 
the  urine  within  half  an  hour  after  the  local  application  of  oil  of  gaultheria. 
Although  the  oil  of  wintergreen  affords  an  effective  method  not  only  for 
locally  acting  upon  rheumatic  inflammations,  but  for  bringing  the  general 
system  under  the  influence  of  the  salicylates,  the  continuing  odor  of  it  is 
so  penetrating  and  offensive  that  some  of  the  newer  preparations  are 
preferable  for  local  use. 

ASPIRIN  (Acetyl-salicy lie  Acid}  occurs  in  white,  crystalline,  insoluble 
needles,  of  an  agreeable  taste,  which  undergo  decomposition  in  alkaline 
fluids  with  the  separation  of  salicylic  acid,  and  are  therefore  changed  by 
the  intestinal  fluids. 

Although  the  urine  affords  evidence  of  the  presence  of  salicylic  acid 
in  half  an  hour  after  the  ingestion  of  aspirin,  according  to  Filippi  and 
Bufalini,  the  excretion  of  the  salicylic  acid  takes  place  much  more  slowly 
than  when  sodium  salicylate  has  been  taken. 

Aspirin  is  undoubtedly  capable  of  acting  physiologically  and  thera- 
peutically  as  a  salicylate.  In  full  doses  it  produces  cinchonism,  and  it 
may  cause  disturbances  of  the  digestion  and  the  other  disagreeable  effects 
of  the  remedies  of  the  class.*  It  is,  however,  usually  better  borne  than 
are  the  older  salicylates,  and  is  probably  somewhat  more  continuing  in 
its  influence,  so  that  it  is  especially  suitable  to  the  treatment  of  sub-acute 
and  chronic  cases,  in  many  of  which,  when  the  symptoms  are  not  severe, 
marked  benefit  may  be  derived  from  the  exhibition  of  a  single  dose  of 
the  aspirin  at  bedtime.  Like  other  salicylates  it  increases  very  markedly 
the  elimination  of  uric  acid  and  other  nitrogenous  excreta  (Singer1). 
It  appears,  however,  to  have  some  peculiarities  in  its  therapeutic  influ- 
ence ;  according  to  Liesan,1  in  large  dose  it  acts  as  a  powerful  sudorific, 
and  many  clinicians  are  concurrent  in  the  statement  that  both  its  anal- 
gesic and  antipyretic  influences  are  much  more  marked  than  is  the  case 
with  most  salicylates.  It  has  been  used  by  various  clinicians  with  as- 
serted good  results  to  depress  temperature  \r\fevers,  and  has  been  highly 
praised  as  a  means  of  subduing  pain  in  migraine,  neuralgia,  and  even  in 
the  fulgurant  agonies  of  locomotor  ataxia. 

*  A  case  has  been  reported  by  Otto  (D.  M.  W.,  1903,  xxix.)  in  which  aspirin  produced 
violent  general  oedematous  erythema,  affecting  also  the  mucous  membranes,  with 
slightly  albuminous  urine,  but  no  fever  and  only  mild  increase  in  the  rapidity  of  the 
pulse  without  irregularity. 


ANTIPYRETICS.  599 

MESOTAN.  Salicylic  acid  methyloxymethylester — This  is  a  yellow,  clear  fluid, 
with  a  slight,  peculiar  odor,  miscible  in  all  proportions  with  ordinary  oils,  which  has 
been  brought  forward  as  a  local  application  in  all  forms  of  rheumatism.  In  from 
half  an  hour  to  an  hour  after  its  local  application  the  presence  of  salicylic  acid  can 
be  demonstrated  in  the  urine.  When  applied  pure  to  the  skin  and  confined  by 
appropriate  dressing  it  is  apt  to  irritate,  so  that  it  should  be  diluted  with  olive  or 
castor  oil.  Glycerine  has  been  used,  but  is  said  not  to  be  advantageous.  From 
one  and  a  half  to  two  and  a  half  drachms  of  mesotan  containing  twenty  per  cent, 
of  the  oil  may  be  applied  daily  to  the  affected  part,  and  then  covered  with  parch- 
ment or  other  impervious  material.  The  application  sometimes  produces  eczema- 
tous,  urticarial,  or  other  eruption,  requiring  its  removal  or  further  dilution. 

GLYCOSAL.  Monosalicylicglycerinester. — This  substance,  originally  prepared 
by  E.  Tauber,  is  a  white  crystalline  powder,  soluble — one  per  cent. — in  cold  water, 
and  freely  in  hot  water  ;  very  soluble  in  alcohol,  decomposed  by  alkalines  and  alka- 
line carbonates,  and  also,  it  is  said,  by  the  intestinal  juices  with  the  separation  of 
salicylic  acid. 

Glycosal  has  been  especially  recommended  as  affording  means  of  treating 
rheumatism  by  external  application.  Zeigan  found  that  from  fifty  to  one  hundred 
grammes  of  its  twenty  per  cent,  alcoholic  solution,  to  which  a  little  glycerin  had 
been  added,  placed  upon  the  rheumatic  part  and  covered  with  oiled  paper,  was 
sufficient  to  produce  in  four  or  five  hours  free  sweating,  lasting  from  a  half  hour 
to  two  hours,  and  in  from  six  to  eight  hours  a  notable  elimination  of  salicylic  acid 
from  the  urine,  with  the  relief  of  the  local  symptoms.  Ratz,  however,  was  unable 
to  secure  absorption  either  by  means  of  the  alcoholic  solution  or  yet  by  inunctions 
made  with  an  indifferent  fatty  basis  ;  although  when  ether,  oil  of  turpentine,  or 
chloroform  was  added  in  the  proportion  of  fifteen  per  cent,  to  the  ointment,  a  nota- 
ble proportion  of  salicylic  acid  appeared  in  the  urine.  R.  Block  finds  that  the  best 
method  of  using  glycosal  is  a  twenty  per  cent,  collodion,  which  he  applies  every 
two  to  four  hours  to  swollen  rheumatic  joints  with  asserted  most  extraordinary  re- 
sults. He  claims  that  if  no  relief  is  afforded  the  inflammation  may  be  positively 
considered  not  to  be  of  rheumatic  origin. 

AMYLIS  SALICYLAS.  Salicylic  Amylester. — A  colorless  liquid  with  a  salol-like 
odor,  soluble  in  ether,  alcohol,  and  chloroform,  almost  insoluble  in  water.  This 
substance  is  an  active  salicylate  which  was  proposed  by  M.  B.  Lyonnet  as  a  substitute 
for  the  oil  of  gaultheria  in  rheumatism,  especially  useful  as  a  local  application  ;  half 
to  one  drachm  applied  to  rheumatic  joints,  and  covered  with  waxed  paper  or  other 
impervious  dressing.  It  has  also  been  used  internally  in  gelatin  capsule,  forty  to 
sixty  minims  a  day. 

SALICIN. — This  is  a  glucoside  of  the  willow  bark  which  has  been  used  in  medi- 
cine, but  is  of  very  feeble  physiological  and  therapeutic  activity,  three  ounces  of  it 
having  been  taken  without  the  production  of  notable  effect.  It  is  readily  absorbed, 
and  is  eliminated  as  salicin,  saligenin,  and  salicylic  acid  (Husemann1).  According 
to  Scarpetti,"  it  inhibits  the  functional  activity  of  the  red  and  white  blood-corpus- 
cles, but  less  powerfully  than  does  quinine.  It  was  originally  introduced  in  the 
treatment  of  specific  and  acute  rheumatism  by  Maclagan,8  but  its  therapeutic  activity 
apparently  depends  upon  the  salicylic  acid  which  is  produced  out  of  it  in  the  sys- 
tem ;  and  as  its  conversion  is  slow  and  imperfect,  as  a  remedy  it  is  of  very  inferior 
value.  At  present  it  is  rarely  used.  Dose,  half  to  one  drachm  (2-4  Gm.). 

SALOPHEN.  Acetylparamidophenyl. — Salophen,  which  contains  50.9  per  cent, 
of  salicylic  acid,  occurs  in  white,  crystalline,  insoluble  leaflets,  and  is  said  to  undergo 
decomposition  in  alkaline  solution.  Siebel  states  that  it  yields  salicylic  acid  in  the 
alkaline  intestinal  juices. 


6oo  GENERAL   REMEDIES. 

It  has  been  largely  used  in  the  treatment  of  all  forms  of  rheumatism,  but  is 
especially  adapted  to  the  subacute  and  chronic  cases.  It  is  capable  of  producing 
cinchonlsm  and  other  salicylic  acid  symptoms,  but  is  less  apt  to  disturb  the  diges- 
tion than  are  the  older  salicylates.  Forty-five  to  seventy-five  grains  of  it  (3-4.85 
Gm. )  may  be  given  in  the  course  of  the  day,  in  divided  doses  in  capsules,  or  better 
diffused  in  milk  or  water. 

ANTIPYRINA.  U.  S.  — PHENAZONUM.  Br.  Ph. 

Phenyl-dimethyl-iso-pyrazolone,  or  antipyrin ,  was  discovered  by  Ludwig 
Knorr,  of  Munich,  and  first  experimented  with  by  Filehne,1  of  Erlangen. 
It  is  a  grayish  or  reddish-white  crystalline  powder,  of  a  slightly  bitter 
taste,  soluble  in  thirty  parts  of  ether,  in  less  than  one  part  of  water,  and 
also  very  soluble  in  alcohol  and  chloroform. 

PHYSIOLOGICAL  ACTION. — Local  Action. — The  local  action  of  anti- 
pyrin  is  not  thoroughly  understood.  It  is  somewhat  irritant,  and  it  is 
alleged  that  it  acts  with  sufficient  power  upon  the  sensory  nerves  to  be 
useful  as  a  practical  local  anaesthetic,  especially  when  applied  to  the 
laryngeal  or  nasal  mucous  membrane.  It  is  also  stated  that  antipyrin  is 
a  very  active  haemostatic,  a  forty  per  cent,  solution  causing  when  applied 
locally  most  active  contraction  of  all  the  small  blood-vessels. 

Saint-Hilaire*  affirms  that  the  anaesthesia  produced  by  antipyrin  is  complete 
and  generally  lasts  from  one  to  two  hours  ;  that  the  sensibility  to  touch  and  also  to 
heat  and  cold  is  destroyed,  the  thermal  sense  returning  first ;  also,  that  the  solution 
must  not  be  of  less  strength  than  thirty  per  cent.,  twenty  per  cent,  solutions  having 
no  anaesthetic  effect.  Huchard  and  Henocque  (quoted  by  Armand)  state  that 
when  they  cut  off  the  feet  of  guinea-pigs  and  put  the  various  stumps  into  a  solution 
of  antipyrin,  of  tincture  of  ferric  chloride,  etc.,  the  bleeding  was  arrested  most 
quickly  by  the  antipyrin. 

Antipyrin  is  absorbed  with  rapidity  and  is  eliminated  through  the  kid- 
neys, partly  as  antipyrin  and  partly  as  a  new  substance  which  is,  accord- 
ing to  Lawrow,48  a  compound  of  oxyantipyrin  with  glycuronic  acid. 

I.  I.  Hage 3  was  unable  to  find  the  drug  in  the  sweat  or  the  saliva,  but  it  has 
been  found  in  minute  quantities  in  the  milk  of  nursing  women  both  by  Pinzani,4and 
by  Fieux.5  Armand  states  that  it  can  be  continuously  detected  in  the  urine  from 
twenty-five  minutes  to  thirty-six  hours  after  its  ingestion,  although  most  of  it  is 
eliminated  in  the  first  twelve  hours.  Ferret  and  Givre6  found  that  urinary  elimina- 
tion begins  in  the  adult  or  in  the  child  three-quarters  of  an  hour  to  an  hour  after  the 
ingestion,  but  that  the  child  eliminates  the  antipyrin  more  rapidly  than  the  adult. 
According  to  Maragliano,7  the  elimination  is  at  its  height  in  four  hours,  and  con- 
tinues for  a  day  and  a  half.  The  urine  is  sometimes  increased,  sometimes  dimin- 
ished, in  quantity  ;  it  is  normal  in  appearance,  and  never  contains  albumin  or  sugar. 

There  is  some  reason  for  believing  that  a  portion  of  the  antipyrin 
undergoes  decomposition  in  the  body,  although  we  have  not  sufficient 
information  upon  the  subject  for  any  positive  conclusion. 

Capitan  and  Gley  8  found  that  the  action  of  the  drug  is  much  less  intense  when 
it  is  thrown  into  the  mesenteric  vein  than  when  it  is  given  by  injection  under  the 


ANTIPYRETICS.  601 

skin  or  into  the  peripheral  vein.  Their  theory,  that  the  liver  retains  or  modifies 
antipyrin,  is  made  more  plausible  by  the  researches  of  Wera  Iwanoff,9  who  finds 
that  the  liver-cells  of  frogs  poisoned  with  antipyrin  undergo  very  pronounced 
changes  in  their  nuclei  and  protoplasm.  The  statements  of  Iwanoff  are  especially 
important  in  connection  with  the  known  effect  of  antipyrin  upon  urea  elimination. 
Disturbances  of  the  hepatic  function  may  be  at  the  basis  of  the  inhibitive  action  of 
the  drug  upon  urea  formation. 

General  Effects. — When  given  to  the  normal  man  in  doses  of  from 
ten  to  twenty  grains,  antipyrin  produces  usually  no  distinct  symptoms. 
If,  however,  it  be  administered  in  a  larger  dose,  and  especially  if  it  be 
given  in  the  continuous  dose,  so  as  to  accumulate  in  the  system,  it  causes 
languor,  malaise,  and  a  peculiar  cyanotic  pallor  of  the  face,  with  failure  of 
the  pulse.  Vomiting  sometimes  occurs.  The  symptoms  which  have  in  a 
number  of  cases  followed  large  doses  are  very  curious,  and  some  of  them 
difficult  of  explanation.  Prominent  among  these  symptoms  is  an  eruption 
on  the  skin,  which  may  occur  without  constitutional  disturbance,  but  is 
often  accompanied  thereby.  In  its  most  typical  form  it  consists  of  small, 
reddish,  irregularly  circular  spots,  resembling  somewhat  those  of  measles, 
and  arranged  in  patches  separated  by  sound  skin.  The  red  color  usually 
disappears  on  pressure,  leaving  a  brown  pigmentation,  which  also  comes 
into  view  during  the  fading  of  the  exanthem,  and  ordinarily  continues 
five  or  six  days.  In  some  cases  the  eruption  is  erythematous  ;  not  rarely 
it  resembles  an  urticaria  in  which  the  white  wheals  may  be  made  very 
prominent  by  a  wide-spread,  deep  crimson  blush. 

In  a  case  reported  by  Spitz 10  the  whole  surface  of  the  body  was  covered  with 
bullae,  which,  becoming  confluent,  involved  the  skin  in  a  universal  desquamative 
inflammation.  Very  frequently  the  antipyrin  rash  is  accompanied  by  wide-spread 
oedema,  which  may  be  most  pronounced  in  the  extremities,  but  is  especially  prone 
to  involve  the  face,  causing  great  swelling,  and  even  closure  of  the  eyes.  The 
mucous  membranes  may  share  in  the  irritation.  Violent  catarrhal  conjunctivitis  is 
not  very  rare,  whilst  coryza  and  laryngitis  have  been  noticed.* 

The  marked  rise  of  temperature  and  disturbance  of  the  circulation 
which  often  accompany  the  antipyrin  eruption  are  probably  due  to  the 
irritation  of  the  skin  and  the  subdermal  tissue,  since,  when  the  anti- 
pyretic eruption  takes  the  form  of  an  urticaria,  the  itching,  sighing,  hys- 
terical unrest,  and  dyspnoea,  which  are  apt  to  accompany  urticarias  not 
due  to  antipyrin,  have  been  very  pronounced. 

In  a  number  of  cases  of  antipyrin-poisoning  there  have  been  violent 
nervous  symptoms,  which  seem  to  be  a  direct  outcome  of  the  action  of 
the  poison.  The  vomiting,  which  is  sometimes  accompanied  by  abdomi- 
nal pain,  may  be  looked  on  as  an  evidence  of  local  irritation  ;  but  this  is 
hardly  the  case  with  giddiness,  somnolence  deepening  into  coma  and 
passing  into  profound  stertorous  unconsciousness,  with  dilatation  of  the 

*For  cases,  see  London  Lancet,  1888,  i. ;  British  Med.  Journ.,  1888,  i. ;  also  1892,  i. 


602  GENERAL  REMEDIES. 

pupils  and  epileptiform  convulsions, — all  of  which  have  been  noted. 
The  unrest,  excitement,  and  violent  tremblings  not  rarely  seen  seem 
also  to  be  directly  produced  by  the  drug.*  H.  M.  Briggs11  reports 
blackish  urine  with  albumin  and  blood-corpuscles  in  antipyrin-poisoning. 

As  illustrative  of  the  symptoms  of  antipyrin-poisoning  may  be  cited  the  case 
reported  by  F.  Spitzer,12  in  which  a  man,  aged  twenty-four,  shortly  after  taking  one 
hundred  and  twenty  grains  of  antipyrin  during  an  hour,  complained  of  violent  pain 
in  the  belly,  and  vomited  freely  ;  an  hour  later  he  was  found  in  a  condition  of  great 
excitement,  screaming,  champing  his  teeth,  with  a  red  face,  much  swollen  conjunc- 
tiva, and  cold  extremities ;  the  pulse  was  108  per  minute,  rhythmical,  with  strong 
heart-impulse  ;  the  respiration  38.  There  was  praecordial  anguish,  pain  in  the 
stomach,  and  marked  tremors,  with  exaggeration  of  the  tendon-reflexes.  Fifteen 
hours  after  the  poisoning  he  was  seized  with  a  sudden  chill,  with  marked  cardiac 
failure,  from  which,  however,  he  recovered. 

The  symptoms  produced  by  antipyrin  upon  the  lower  animals  resem- 
ble those  caused  in  man,  except  in  the  absence  of  dermal  irritation  and 
its  secondary  results. 

According  to  the  observations  of  Leon  Arduin,13  Demme,1*  Coppola,15  Simon 
and  Hock,16  and  others,  in  the  frog,  in  moderate  toxic  doses  (half  to  one  centi- 
gramme), it  causes  convulsions,  with  opisthotonos,  and  a  very  marked  increase  of 
reflex  activity.  In  the  earlier  stages  of  this  condition  the  animal  is  cataleptic,  and 
L.  Blumeneau  "  affirms  that  there  is  a  primary  stage  of  quiet  with  diminished  reflex 
activity.  If  given  in  overwhelming  amount,  antipyrin  causes  in  the  frog  immediate 
quiet,  muscular  relaxation,  with  loss  of  reflex  activity,  deepening  into  complete 
paralysis  and  death.  In  mammals  the  chief  symptoms  of  antipyrin-poisoning  are 
ataxy,  paraplegia,  hurried  respiration,  convulsions  with  general  rigidity,  dilated 
pupils,  unconsciousness,  and  fall  of  temperature,  ending  in  death,  which  seems 
to  be  due  to  failure  of  respiration. 

Nervous  System. — The  quietness  produced  by  therapeutic  doses  of 
antipyrin,  and  the  cerebral  symptoms  of  antipyrin-poisoning,  show  that 
the  drug  has  a  peculiar  influence  upon  the  cerebral  cortex.  Simon  and 
Hock  believe  that  their  experiments  prove  that  the  special  senses  are 
first  stimulated  and  then  paralyzed.  The  convulsions  of  antipyrin-poi- 
soning are  probably  in  part  epileptiform  (i.e. ,  of  cerebral  origin)  and  in 
part  tetanic  (i.e.,  of  spinal  origin),  though  the  testimony  concerning  this 
matter  is  contradictory. 

Blumeneau  and  Batten  and  Bokenham 18  state  that  section  of  the  cord  does  not 
prevent  the  occurrence  of  the  convulsions  in  the  posterior  segment  of  the  body ; 
while  Coppola  and  Simon  and  Hock  state  that  it  has  such  action.  Either  the  first- 
named  observers  failed  to  make  complete  section  or  else  both  cerebral  and  spinal 
convulsions  are  produced  by  the  drug. 

Our  knowledge  of  the  action  of  antipyrin  upon  the  spinal  cord  is  very 
incomplete.  We  do  not  certainly  know  whether  the  alleged  primary 

*See  Berlin.  Klin.  Wochensch.,  1889,  xxvi. ;  Med.  News,  1889,  liv.  ;  Correspond. 
Blatt.,  1888. 


ANTIPYRETICS.  603 

decrease  of  reflex  activity  (Blumeneau),  or  the  characteristic  increase  of 
reflex  activity  (various  observers),  or  the  final  abolition  of  reflex  activity 
are  or  are  not  of  spinal  origin,  although  it  is  probable  that  in  toxic  doses 
the  drug  acts  as  a  primary  stimulant  and  a  secondary  depressant  of  the 
spinal  cord. 

Chouppe 19  states  that  the  drug  even  has  the  power  of  suspending  the  strychnic 
convulsions.  If  the  observation  of  Blumeneau — that  in  a  frog  with  the  cerebral 
hemispheres  removed  antipyrin  produced  slowness  of  reflex  reaction,  which  imme- 
diately disappeared  upon  section  of  the  spinal  cord  high  up — be  correct,  the  primary 
reflex  depression  is  probably  cerebral. 

There  seems  to  be  no  doubt  that  antipyrin  paralyzes  both  the  motor 
and  the  sensory  nerves. 

Lepine 20  has  noticed  that  if  access  to  a  motor  nerve  be  shut  off,  such  nerve, 
after  death  from  antipyrin,  will  be  distinctly  more  active  in  its  response  to  stimuli 
than  is  the  implicated  nerve  ;  whilst  Simon  and  Hock  noted  in  frogs  killed  with 
antipyrin  the  motor  nerves  absolutely  paralyzed,  and  have  also  demonstrated  the 
influence  of  the  drug  by  bringing  it  in  local  contact  with  an  exposed  nerve.  These 
latter  observers  further  confirm  the  earlier  work  of  Coppola,  and  it  seems  to  be 
proved  that  when  applied  locally,  or  given  internally,  antipyrin  is  a  distinct  de- 
pressant of  the  sensory  nerve-trunks.  Simon  and  Hock  state  that  in  the  beginning 
of  the  convulsive  stage  animals  can  be  operated  upon  without  the  use  of  an 
anaesthetic. 

How  far  the  vaso-motor  and  other  nerves  connected  with  the  involun- 
tary movements  of  the  body  are  influenced  by  antipyrin  is  at  present 
uncertain,  although  there  is  some  reason  to  suspect  that  the  drug  acts 
upon  them  as  it  does  upon  the  nerves  connected  with  voluntary  life. 

According  to  Batten  and  Bokenham,  when  locally  applied  to  the  exposed  intes- 
tine, antipyrin  prevents  the  peristaltic  wave  which  is  normally  produced  by  the  ap- 
plication of  common  salt,  although  it  does  not  check  the  annular  contraction  at  the 
point  of  irritation  ;  an  effect  which  seems  explainable  only  by  the  supposition  that 
the  intestinal  nerves  and  not  the  intestinal  muscles  are  paralyzed  by  the  drug. 

Muscles. — According  to  Devraux-Armand,21  the  muscular  stiffness 
of  advanced  antipyrin-poisoning,  when  the  poisoning  is  fatal,  passes 
directly  into  post-mortem  rigidity.  Moreover,  in  Armand's  researches 
the  contractions  of  muscles  taken  from  the  body  of  animals  killed  with 
antipyrin  were  much  more  powerful  and  prolonged  than  were  those  pro- 
duced by  the  same  amount  of  stimulation  in  the  normal  muscle. 

Circulation. — Demme,  Arduin,  Armand,  Henry  Casimir,"  and  Cerna 
and  Carter 23  have  separately  determined  by  experiment  that  in  moderate 
doses  antipyrin  increases  the  arterial  pressure,  while  toxic  doses  lower  the 
pressure.  The  cause  or  causes  of  the  rise  have  not  yet  been  fully  deter- 
mined ;  it  occurs  in  curarized  animals,  and  is  therefore  independent  of 
any  action  of  the  drug  upon  the  respiratory  centre.  According  to 
Cerna  and  Carter,  it  is  not  prevented  by  previous  section  of  the  pneumo- 


604  GENERAL   REMEDIES. 

gastric  nerves  and  of  the  spinal  cord,  and  the  pulse- waves  accompanying 
it  are  of  extraordinary  size  and  height.  It  would  appear,  therefore,  that 
it  is  at  least  in  part  due  to  a  direct  stimulation  of  the  heart.  Unfortunately, 
however,  the  evidence  which  we  have  at  present  is  so  contradictory  that 
no  positive  conclusions  can  be  drawn  as  to  the  effect  of  the  largest  thera- 
peutic dose  of  antipyrin  upon  the  heart,  whilst  in  regard  to  the  toxic 
doses  it  is  more  than  probable  that  they  directly  depress  the  heart. 

Arduin,  Demme,  Lepine,  and  Armand  all  affirm  that  in  the  poisoned  frog  the 
heart  is  arrested  in  diastole,  but  Coppola  states  that  antipyrin  has  no  influence  upon 
the  circulation  in  the  frog,  that  in  many  cases  after  the  largest  dose  the  heart  is 
arrested  in  systole,  and  that  in  the  Williams  apparatus  no  effect  is  produced  by 
antipyrin  upon  the  isolated  heart  unless  the  dose  be  enormous.  Faval  '-14  found, 
however,  that  while  moderate  doses  have  little  effect,  large  doses  diminish  the  fre- 
quency and  force  of  the  cardiac  contractions  in  the  isolated  heart  of  the  frog,  and 
finally  cause  diastolic  arrest. 

The  action  of  the  drug  upon  the  vaso-motor  system  is  at  present 
writing  very  doubtful.  Cerna  and  Carter  affirm  that  it  has  no  influence 
upon  the  blood-vessels,  but  give  no  proof  of  this  ;  and  the  fact  ascer- 
tained by  Casimir,  that  the  rise  of  arterial  pressure  is  accompanied  by  a 
distinct  decrease  in  the  size  of  such  vascular  internal  organs  as  the  kid- 
neys, indicates  that  the  drug  produces  a  vaso-motor  spasm,  a  view  which 
receives  confirmation  from  the  assertion  of  Arduin,  that  antipyrin  is  a 
powerful  local  haemostatic.  On  the  other  hand,  Querrolo  (quoted  by 
Armand),  employing  the  plessimograph  of  Mosso,  found  that  the  arm  is 
increased  in  size  under  the  influence  of  antipyrin,  and  therefore  that  the 
peripheral  vessels  are  dilated,  and  Casimir  affirms  that  similar  dilatation  can 
be  seen  in  the  blood-vessels  of  the  ears  of  rabbits  poisoned  by  antipyrin. 

The  fall  of  the  arterial  pressure  is  without  doubt,  at  least  in  part,  the 
result  of  a  depressing  influence  of  the  drug  upon  the  heart  itself ;  but  if 
the  observation  of  Bettelheim  (quoted  by  A.  Biach25),  that  during  the 
fall  of  blood-pressure  the  temperature  of  the  interior  of  the  body  notably 
falls,  while  that  of  the  exterior  correspondingly  rises,  be  correct,  vaso- 
motor  paralysis  probably  is  also  a  factor. 

According  to  the  researches  of  Cerna  and  Carter,  the  pulse  is  usually 
increased  in  rate  by  full  doses  of  antipyrin  through  a  paralytic  influ- 
ence upon  the  inhibitory  nerves,  but  afterwards  becomes  decreased  in 
number  through  the  direct  action  of  the  drug  upon  the  heart  itself. 

The  peculiar  lividity  often  seen  in  persons  under  the  influence  of  anti- 
pyrin is  probably  due  to  changes  in  the  blood  itself.  According  to 
Lepine,  methasmoglobin  is  largely  formed  during  the  poisoning,  but 
Crolas  and  Hagoumeng  x  failed  to  detect  it.  The  three  observers  are  in 
accord  in  finding  that  the  number  of  the  red  corpuscles  is  not  perceptibly 
affected,  even  by  the  continuous  exhibition  of  very  large  doses. 

Temperature. — When  given  in  large  doses  to  the  normal  animal, 
antipyrin  frequently,  but  not  invariably,  produces  fall  in  the  bodily  tem- 
perature ;  in  the  fevered  animal  this  fall  is  more  marked  and  more  con- 


ANTIPYRETICS.  605 

stant.  Its  cause  is  not  entirely  established,  but  it  is  probably  the  result 
of  an  influence  exerted  directly  upon  the  thennogenetic  centres.  It  is 
certainly  independent  of  any  action  upon  the  general  circulation,  as  we 
have  seen  the  temperature  of  fevered  dogs  reduced  four  or  five  degrees 
by  antipyrin  without  change  in  the  arterial  pressure. 

In  seven  out  of  nine  experiments  made  by  H.  C.  Wood,  EL  T.  Reichert,  and  Ho- 
bart  A.  Hare*"  upon  normal  animals,  there  was  a  decrease  in  both  the  production 
and  the  dissipation  of  animal  heat.  In  two  experiments  both  functions  were  dis- 
tinctly increased.  When  tetanic  convulsions  occur  from  antipyrin  there  is  a  marked 
rise  of  the  bodily  temperature.  In  both  of  the  calorimetric  experiments  in  which 
the  heat-production  was  increased,  very  large  doses  of  antipyrin  had  been  given, 
and  it  is  believed  that  the  animal  suffered  convulsions  in  the  calorimeter.  In  almost 
all  the  experiments  the  decrease  of  heat-production  was  very  much  greater  than 
the  decrease  of  heat-dissipation  :  it  would  appear,  therefore,  that  antipyrin  in  the 
normal  dog  primarily  lessens  heat-production,  the  reduction  of  the  heat-dissipation 
probably  being  the  result,  at  least  in  part,  of  the  lessened  heat-production.  In  ex- 
periments upon  dogs  in  which  fever  bad  been  produced  by  injections  of  pepsin, 
both  heat-production  and  heat-dissipation  were  markedly  decreased,  but  usually 
heat-production  was  more  affected  than  was  heat-dissipation. 

The  experiments  of  Destree  **  and  of  Engel  (quoted  by  Biach)  are. 
so  far  as  they  go,  in  accord  with  those  just  given,  whilst  Cerna  and  Carter 
found  pronounced  decrease  of  heat-production  with  simultaneous  increase 
of  heat-dissipation  in  dogs  fevered  by  injections  of  putrid  blood  ;  so  that 
it  would  appear  that  antipyrin  reduces  temperature  in  fever  by  decreasing 
the  heat-production,^  That  antipyrin  acts  through  the  nervous  system  is 
strongly  indicated  by  the  influence  which  it  has  over  fever  produced  by 
nerve-lesions. 

P.  J.  Martin,19  R.  Gottlieb,"  and  H.  Girard M  are  in  accord  in  finding  that  the 
rise  of  temperature  which  is  produced  in  the  rabbit  by  punctures  in  the  neighbor- 
hood of  the  striate  body  is  lessened  or  altogether  put  aside  by  antipyrin.  Martin 
has  further  found  that  heat-production  is  also  lessened  under  these  circumstances. 
Gottlieb  **  states  that  Sawadowski  has  determined  that,  in  the  dog  whose  spinal 
cord  is  cut  high  up,  antipyrin  no  longer  reduces  the  temperature. 

*  The  course  of  fever  produced  by  inje^ions  of  pepsin  in  the  blood  varies,  and  in 
calorimetric  experiments  it  is  not  sufficient  to  give  pepsin  and  when  the  temperature  has 
risen  administer  the  antipyretic  and  study  calorimetrically  the  result.  The  best  way  is 
to  produce  a  paroxysm  of  fever  on  one  day  and  study  it  calorimetrically  through  its  whole 
course ;  some  days  subsequently,  the  same  animal  and  dose  of  pepsin  being  used,  the 
course  of  the  fever  is  to  be  modified  by  the  antipyretic,  and  the  heat-dissipation  and  heat- 
production  of  the  two  days  contrasted. 

t  The  experiments  of  Gottlieb,  however,  are  not  consonant  with  this  view ;  in  three 
experiments  hypodermic  injections  of  antipyrin  were  followed  by  increased  heat-produc- 
tion, with  a  greater  increase  of  heat-dissipation  and  consequent  fall  of  temperature.  Sim- 
ilar results  were  also  reached  in  rabbits  in  which  fever  had  been  produced  by  pricking 
nerve-centres  (Arckiof.  Erpfr.  Pat*.  «.  P*arm.,  1891,  xxviii.).  These  experiments  are 
certainly  open  to  the  objection  that  it  is  not  shown  that  the  changes  in  heat-dissipation 
and  production  which  were  noted  were  really  produced  by  the  antipyrin.  and  were  not 
due  to  the  confinement  in  the  calorimeter  or  to  the  natural  variations  in  the  course  of  the 
fever  itself;  in  other  words,  there  were  no  proper  control  experiments. 


606  GENERAL  REMEDIES. 

The  studies  which  have  been  made  by  chemists  as  to  the  effects  of 
antipyrin  upon  the  elimination  of  waste  products,  taken  as  a  whole,  are  in 
accord  with  the  view  that  antipyrin  lessens  heat-production.  It  is  indeed 
true  that  Chittenden  and  Cummins83  were  unable  to  find  that  antipyrin, 
either  in  large  or  in  toxic  doses,  has  any  effect  upon  the  elimination  of 
carbonic  acid  by  the  animal  ;  but  before  these  results  can  be  considered 
as  established  further  experimentation  is  necessary.  Again,  Armand 
thought  that  he  had  chemically  proved  that  antipyrin  increases  the  elimi- 
nation of  urea  ;  but  the  original  studies  of  Umbach,34  who  found  that 
large  doses  of  antipyrin  very  markedly  decrease  the  elimination  of  urea, 
have  been  so  abundantly  confirmed*  that  it  would  seem  that  it  must  be 
considered  established  that  antipyrin,  both  in  health  and  in  fever,  dimin- 
ishes the  output  of  the  nitrogenous  products  of  tissue-waste.^ 

Antiseptic  Influence. — The  influence  of  antipyrin  upon  pathogenic 
micro-organisms  and  upon  fermentation  has  been  elaborately  studied  by 
Engel  (quoted  by  Biach),  who  found  that  such  influence  is  so  exceed- 
ingly feeble  as  to  have  for  practical  purposes  no  existence.  On  the  other 
hand,  Chittenden  and  Stewart  state  that  antipyrin  inhibits,  and  if  present 
to  the  amount  of  three  per  cent,  stops,  the  digestive  action  of  the  acidu- 
lated pepsin  solution,  whilst  Cazeneuve  and  Visbeck S5  find  that  one  per 
cent,  of  antipyrin  is  sufficient  to  indefinitely  put  off  putrefaction  of  the 
blood.  They  also  confirm  the  fact  that  antipyrin  is  capable  of  inhibiting 
the  action  of  ferments  like  pepsin  and  diastase.  Roux  and  Rodet 36  find 
that  a  four  per  cent,  solution  is  sufficient  to  very  sensibly  affect  the  Ba- 
cillus coli  communis. 

SUMMARY. — Antipyrin  is  absorbed  rapidly,  and  eliminated  rapidly, 
at  least  in  part,  unchanged.  Whilst  the  ordinary  dose  of  antipyrin  pro- 
duces no  distinct  symptoms,  when  in  large  enough  amount  the  drug 
causes  languor,  malaise,  cyanosis,  depression  of  the  circulation,  giddi- 
ness, somnolence,  epileptiform  convulsions,  a  measle-like  exanthema, 
coma,  and  collapse.  Owing  to  idiosyncrasy,  it  provokes  in  some  cases 
violent  urticaria  and  subdermal  inflammation,  which  may  be  accom- 
panied by  fever  and  other  constitutional  disturbances.  It  is  probably 
a  primary  stimulant  and  a  secondary  depressant  of  the  motor  spinal 
cord.  It  is  certainly  a  paralyzant  to  both  the  motor  and  sensory  nerve- 
trunks,  and  seems  to  have  also  some  action  upon  the  muscles  them- 
selves. A  small  dose  may  moderately  increase  arterial  pressure,  prob- 
ably by  directly  stimulating  the  heart  and  the  blood-vessels,  although 
upon  these  points  we  have  no  certain  knowledge.  The  final  fall  of 

*  Among  the  chemists  who  have  reached  this  conclusion  by  practical  experimentation 
may  be  mentioned  Wiczkowski  (quoted  by  Umbach),  Walter,  of  St.  Petersburg  (  Therap. 
Ga.2.,  ii.),  F.  Miiller  (Jahresb.fiir  Thierchemie,  xiv.),  Ries  (quoted  by  Biach),  Albert 
Robin  (Bull.  Acad.  Med.,  1887,  xviii.),  and  Jacubovitsch  (Brit.  Med.  Journ.,  1888,  ii.). 
Tausk's  (Schmidt's  Jahrb.,  ccxxxvi.)  failure  to  get  a  pronounced  effect  may  have  been 
due  to  his  having  used  too  small  doses. 

t  It  would  further  appear  probable  that  antipyrin  alters  the  normal  relation  between 
the  various  excrementitious  substances,  since  Umbach  has  found  that  while  the  urea  was 
markedly  diminished,  uric  acid  was  scarcely  altered  ;  and  Robin  affirms  that  in  his  ex- 
periments the  elimination  of  uric  acid  was  even  augmented. 


ANTIPYRETICS.  607 

arterial  pressure  is  due,  at  least  in  part,  to  a  direct  action  upon  the 
heart.  In  sufficient  amount  antipyrin  causes  methaemoglobin  to  ap- 
pear in  the  blood.  It  increases  the  respiratory  rate  by  a  centric  action. 
It  probably  lessens  the  production  of  animal  heat  by  a  direct  action 
through  the  nervous  system,  independent  of  any  influence  upon  the 
circulation,  and  appears  also  to  stimulate  heat-dissipation.  Both  in 
health  and  in  fever  it  diminishes  the  output  of  the  nitrogenous  products 
of  tissue-waste. 

THERAPEUTIC  ACTION. — In  fever  cases,  about  half  an  hour  to  an 
hour  after  the  ingestion  of  a  full  antipyretic  dose  of  antipyrin  profuse 
sweating  occurs,  and  is  soon  followed  by  a  fall  of  temperature,  which  is, 
however,  independent  of  the  diaphoresis. 

According  to  Carl  von  Noorden,"  the  sweating  can  be  arrested  by  the  use  of 
hypodermic  injections  of  atropine  or  agaricin  without  affecting  the  fall  of  tem- 
perature. Moreover,  the  sweating  is  not  invariably  present,  and  in  dogs,  which 
practically  do  not  sweat,  antipyrin  is  a  powerful  antipyretic  in  fever. 

According  to  most  authorities,  the  depression  of  temperature  lasts 
longer  than  that  caused  by  some  other  antipyretics,  continuing  from  two 
to  ten  hours.  It  is  accompanied  by  a  reduction  of  the  rate  but  not  usu- 
ally of  the  force  of  the  pulse.  In  some  cases  the  sweating  is  not  profuse, 
and  it  is  probably  under  such  circumstances  that  observers  have  noticed 
a  markedly  increased  diuresis.  Usually  the  patient  is  more  comfortable 
under  the  action  of  the  drug  than  at  other  times  ;  sometimes,  however, 
there  is  distressing  vomiting. 

Antipyrin  may  be  employed  as  an  antipyretic  in  almost  any  disease 
accompanied  by  high  temperature,  such  as  pneumonia,  erysipelas,  and 
typhus,  scarlet,  yellow,  and  typhoid  fevers,  rheumatism,  etc. ;  it  has  also 
been  freely  given  in  the  hectic  fever  of  phthisis,  but  various  observers 
state  that  in  such  cases  it  produces  so  much  feebleness  and  general  de- 
pression as  to  forbid  its  use  :  nevertheless,  our  own  observation  is  that 
when  used  with  caution  it  often  gives  great  relief.  In  typhus  fever  it 
reduces  the  temperature,  but  in  a  number  of  recorded  cases  it  has  in- 
duced very  serious  collapse.  It  appears  to  have  some  specific  action 
in  rheumatism,  but  does  not  in  this  respect  equal  salicylic  acid.  Accord- 
ing to  A.  Pribram,38  in  pneumonia  the  frequency  of  the  respiration  is  dis- 
tinctly lessened  by  it,  but  this  is  probably  due  simply  to  the  lowering  of 
the  bodily  temperature.  In  children  it  has  been  used  with  asserted  good 
results  by  a  number  of  clinicians,  and  it  appears  to  be  especially  useful  in 
the  pneumonia  and  bronchitis  of  the  young. 

The  second  indication  for  the  meeting  of  which  antipyrin  is  some- 
times used  with  success  is  the  relief  of  motor  disturbance.  Over  the 
minor  spasmodic  conditions  of  hysterical  origin,  over  chorea,  etc. ,  anti- 
pyrin has  a  certain  amount  of  power.  In  1888  Sonnenberger M  com- 
mended it  very  highly  in  whooping-cough,  stating  that  if  given  at  regular 


6o8  GENERAL  REMEDIES. 

intervals  it  greatly  lessens  the  number  of  paroxysms,  or  even  aborts  the 
disease  ;  and  further  clinical  experience  seems  to  show  that  the  drug  has 
real  value.  M.  A.  Chouppe  states  that  antipyrin  has  great  power  in 
relieving  uterine  pains  after  parturition  or  in  dysmenorrhcea,  and  that  if 
it  be  given  during  labor  along  with  ergot  it  allows  the  contractions  to  go 
on,  but  renders  them  painless.  In  more  severe  spasmodic  disorders 
antipyrin  sometimes  does  good.  It  is  certainly  worthy  of  trial  in  tetanus, 
especially  when  the  temperature  is  high.  It  may  be  given  in  epilepsy 
with  some  hope  of  success,  since  its  influence  in  preventing  the  return 
of  convulsions  is  sometimes  extraordinary,  although  in  the  great  majority 
of  cases  it  fails  entirely.  We  have  studied  it  in  a  large  number  of  cases, 
but  are  unable  to  point  out  any  indications  which  will  warrant  in  an  indi- 
vidual case  an  a  priori  opinion  that  antipyrin  will  do  good.  The  only 
method  is  that  of  trial.  Not  less  than  forty  grains  a  day  should  be  given, 
and  if,  after  a  time,  no  cyanosis  or  muscular  weakness  mark  the  physio- 
logical action  of  the  drug,  and  the  convulsions  still  recur,  the  dose  should 
be  increased  up  to  the  physiological  limit.  The  combination  of  anti- 
pyrin with  ammonium  bromide  affords  much  better  results  than  either 
drug  alone,  and  it  has  become  with  us  a  routine  practice  to  prescribe  in 
epilepsy  a  mixture  of  ammonium  and  strontium  bromide  with  antipyrin. 
We  have  given  to  a  large  number  of  cases  fifteen  grains  daily  of  the  anti- 
pyrin in  this  combination  for  many  months,  and  even  for  years,  without 
cumulative  action  or  perceptible  effect  upon  the  general  nutrition  or  the 
general  nerve  functions,  except  that  in  some  cases,  probably  by  disturb- 
ance of  thermogenesis,  a  condition  of  such  intolerance  of  cold  is  produced 
that  the  drug  has  to  be  withdrawn,  at  least  for  a  time.  Antipyrin  has 
been  used  with  alleged  success  in  laryngismus  stridulus,  in  nocturnal 
emissions,  in  asthma,  and  in  urinary  incontinence  of  children. 

The  third  indication  which  may  sometimes  be  advantageously  met 
by  antipyrin  is  the  relief  of  pain.  In  April,  1887,  See  announced  to 
the  French  Academy  of  Medicine  that  antipyrin  is  a  powerful  analgesic, 
which  when  given  in  doses  of  from  forty-five  to  ninety  grains  a  day  will 
control  almost  all  forms  of  pain.  Such  doses,  however,  border  upon 
toxic,  and  are  rarely  justifiable.  Moreover,  they  are  scarcely  ever 
necessary  in  properly  selected  cases.  Abundant  clinical  experience  has 
shown  that  antipyrin  for  the  relief  of  ordinary  inflammatory  pains  is  not 
reliable,  and  is  in  every  respect  inferior  to  opium  ;  but  that  it  is  a  very 
valuable  agent  against  various  nervous  pains,  sometimes  giving  much 
more  relief  than  does  opium,  and  usually  causing  less  disturbance  to  the 
system.  Especially  is  it  effective  in  rheumatic  pains  and  in  migraine 
and  other  forms  of  neuralgia  in  which  the  pain  is  the  outcome  of  nerve- 
storm  ;  it  will,  indeed,  often  control  the  pangs  of  locomotor  ataxia ;  we 
have  even  seen  it  abort  a  gastric  crisis.  Whether  it  acts  by  a  true 
analgesic  influence,  or  whether  it  simply  puts  aside  the  nerve-storm 
which  is  the  cause  of  the  pain,  is  entirely  unknown.  In  violent  hemi- 
crania  sleep  follows  relief ;  but  antipyrin  is  not  a  true  hypnotic.  Anti- 


ANTIPYRETICS.  609 

pyrin  is  stated  greatly  to  increase  the  analgesic  effects  of  morphine,  and 
is  itself,  in  headache  at  least,  made  much  more  effective  by  caffeine. 

Antipyrin  has  also  been  used  in  various  disorders  not  included  under 
the  indications  already  given,  often  without  sufficient  reason. 

M.  H.  Feeny  *°  reports  subacute  Bright' s  disease  cured  by  it ;  Clement,41  that 
it  is  of  value  in  bringing  about  absorption  of  pleuritic  effusions.  Both  in  diabetes 
mellitus  and  diabetes  insipidus  it  has  been  used  with  asserted  good  results.  Saint- 
Phillippe 42  commends  it  highly  in  infantile  diarrhoea  with  indigestion  and  pain. 
Salemi  affirms  that  it  is  an  active  and  practical  antigalactagogue,  and  in  this  has 
been  confirmed  by  Ryan-Tennison  and  by  Guibert.4* 

ADMINISTRATION. — Antipyrin  may  be  administered  hypodermically, 
by  the  mouth,  or  by  the  rectum.  The  dose  for  a  child  of  one  or  two 
years  of  age  may  be  set  down  as  two  to  three  grains  (0.13-0.2  Gm. )  ; 
for  a  child  five  years  old,  three  to  seven  grains  (0.2-0.46  Gm. )  ;  for  the 
adult  the  dose  should  not  exceed  twenty  grains  (1.3  Gm. ),  and  ten  grains 
(o.  6  Gm. )  are  usually  sufficient,  in  fever  cases,  repeated  every  one  or  two 
hours  until  forty  grains  are  given,  or  sweating  comes  on,  or  the  tem- 
perature falls.  In  children  it  would  not  be  safe  to  repeat  the  dose  more 
than  once.  Some  authorities  prefer  a  single  large  dose  of  from  forty  to 
sixty  grains  (2.5-4  Gm. )  in  the  adult. 

Hypodermic  Use. — Antipyrin  has  been  used  to  a  considerable  extent 
hypodermically  for  the  relief  of  pain,  and  in  neuralgias  and  nerve-pains 
good  can  sometimes  be  achieved  by  its  local  influence.  The  burning 
pain  produced  by  the  injection  of  a  thirty  per  cent,  solution  usually  lasts 
only  a  few  minutes,  and  is  not  followed  by  local  inflammation.  Verneuil,44 
however,  has  reported  partial  gangrene  of  the  foot  following  and  appar- 
ently produced  by  a  hypodermic  injection  of  antipyrin  for  the  relief  of 
sciatic  neuritis. 

TOXICOLOGY. — In  describing  the  action  of  antipyrin  upon  the  normal 
human  organism,  sufficient  has  been  said  in  regard  to  the  general  symp- 
toms produced  by  poisonous  doses.  It  seems  necessary,  however,  to 
point  out  that  these  symptoms  in  a  large  proportion  of  recorded  cases 
seem  to  have  been  due  to  constitutional  peculiarities  of  the  individual 
rather  than  to  the  use  of  very  large  doses  of  antipyrin,  and  they  are 
rarely,  if  ever,  attended  by  any  danger  to  life.  Thus,  E.  W.  Young45 
reports  a  serious  poisoning  by  six  grains  of  antipyrin.  Theo.  Schwabe  ** 
reports  a  case  in  which  fifteen  grains  of  antipyrin,  given  to  a  young 
woman  for  neuralgia,  produced  violent  poisoning  with  collapse,  complete 
amauro&is,  cyanosis,  urticaria,  etc.  Almost  equally  inexplicable  are 
those  cases  which  have  especially  occurred  in  typhoid  and  other  fevers, 
in  which  fatal  depression  has  been  produced  by  doses  of  antipyrin  that 
were  not  larger  than  have  frequently  been  used  without  evil  results. 
Thus,  in  Barrs's47  case,  thirty-five  grains  of  antipyrin  were  given  to  a 
puerperal  woman  with  a  temperature  of  103.6°  F.,  and  followed  in  three 
hours  by  half  the  quantity,  after  which  the  temperature  sank  to  98°  F. , 

39 


6io  GENERAL  REMEDIES. 

and,  in  spite  of  stimulation,  death  occurred  thirty-two  hours  later.  Our 
knowledge  of  the  physiological  action  of  antipyrin  seems  to  negative  the 
supposition  that  the  depression  in  these  fever  cases  is  due  to  any  direct 
action  upon  the  heart  or  other  vital  organ.  Heat  is  a  stimulant  to  func- 
tion, and  it  may  be  that  the  cause  of  the  collapse  is  the  sudden  fall  of 
bodily  temperature  in  a  person  whose  nervous  system  is  excessively  en- 
feebled by  a  fever  of  typhoid  nature. 

ACETOPYRIN.  Antipyriiuz  Aceto-salicylas. — This  occurs  as  a  white  crystalline 
powder,  having  an  odor  resembling  acetic  acid  ;  sparingly  soluble  in  cold,  but 
freely  in  warm  water  ;  freely  soluble  in  alcohol,  chloroform,  and  in  warm  toluol, 
less  so  in  ether  and  in  petroleum-ether. 

It  was  originally  introduced  into  medicine  by  Winterberg  and  Braun *  as  com- 
bining the  activities  of  antipyrin  and  salicylic  acid,  into  which  substances,  according 
to  W.  Meitner,1  it  is  broken  up  in  the  stomach  ;  the  aspirin  undergoing  further 
decomposition  in  the  intestines. 

Acetopyrin  has  been  much  used  as  an  analgesic  in  migraine,  sciatica,  neuritis, 
and  also  as  an  antipyretic  in  typhoid  and  other  low  fevers.  Also  as  an  antirheu- 
matic  of  especial  value  in  subacute  and  chronic  cases.  Its  physiological  and 
therapeutic  activities  are  probably  those  of  its  constituents.  It  may  be  given  in 
doses  of  five  to  ten  grains  in  capsules,  or  suspended  in  water,  and  repeated  up  to 
thirty  grains  in  the  twenty-four  hours  when  necessary.  In  fevers  two  doses  may 
be  given  two  hours  apart  about  the  time  of  the  exacerbation. 

EUPYRINE.  Para-phenitidine-vanillin-ethyl-carbonate. — This  substance,  which 
occurs  in  pale  greenish-yellow  tasteless  needles,  having  an  odor  suggestive  of 
vanilline,  is  sparingly  soluble  in  water,  but  dissolves  freely  in  alcohol.  It  was  intro- 
duced into  medicine  by  Overlach J  as  a  non-toxic  antipyretic,  which  will  produce 
in  fevers  apyrexia  without  excessive  sweating  or  nervous  disturbances.  It  is 
affirmed  that  a  fall  of  i°  to  3°  F.  may  be  caused  with  it  not  only  without  depres- 
sion, but  with  the  production  of  euphoria.  The  statements  of  Overlach  have  been 
confirmed  by  O.  Forges,2  and  the  drug  is  affirmed  to  be  especially  valuable  in  the 
treatment  of  old  people  and  children,  and  in  such  conditions  as  that  of  influenza 
with  fever.  Eupyrine  is  said  to  have  no  analgesic  properties.  Dose,  fifteen  to 
twenty-four  grains  (1-1.5  Gm. )  for  adults;  for  children,  five  to  eight  grains 
(0.3-0.5  Gm.). 

ACETANILIDUM— ACETANILID.     U.  S. 

Antifebrin,  or  phenylacetamide,  is  an  aniline  in  which  one  atom  of 
hydrogen  has  been  replaced  by  the  radical  acetyl ;  or  it  may  be  consid- 
ered as  an  ammonia  in  which  one  atom  of  hydrogen  is  replaced  by  phenol 
and  another  atom  by  acetyl.  It  is  a  white,  crystalline  substance,  entirely 
without  odor,  having  a  bitter,  mildly  piquant  taste.  It  is  soluble,  at  59° 
F. ,  in  one  hundred  and  ninety-four  parts  of  water  and  in  five  parts  of 
alcohol. 

PHYSIOLOGICAL  ACTION. — Local  Action. — According  to  the  experi- 
ments of  L.  Frothingham  and  J.  H.  Pratt,1  acetanilid  is  distinctly  antag- 
onistic to  disease  germs,  scarcely  killing  them,  but  markedly  inhibiting 
their  growth.  Applied  in  the  form  of  powder  to  a  wound  or  mucous 
membrane,  it  acts  as  a  stimulant  or  feeble  irritant,  a  desiccant,  and  proba- 
bly also  as  an  analgesic. 


ANTIPYRETICS.  611 

Absorption  and  Elimination. — Absorbed  into  the  blood  by  some  un- 
known method,  acetanilid  is  in  great  part  or  altogether  converted  into 
the  paramidophenol  sulphate,*  and  as  such  escapes  from  the  kidney.  It 
is  probable  that  it  breaks  up  in  the  organism  into  acetic  acid  and  aniline, 
and  that  the  aniline  is  then  oxidized  into  paramidophenol,  which  unites 
with  sulphuric  acid.f 

Cahn  and  Hepp,1  however,  affirm  that  antifebrin  escapes  finally  with  the  urine 
in  great  part  unaltered,  and  that  only  a  small  portion  of  it  is  converted  into  aniline 
and  acetic  acid ;  but  Miiller  as  well  as  Pavai  Vajna  *  and  Kumagawa  *  state  that 
antifebrin  cannot  be  found  in  the  urine,  and  consequently  that  it  undergoes  entire 
decomposition.  Jaffe  and  Hilbert8  found  that  in  dogs  acetanilid  passes  off  chiefly 
as  o-oxycarbonol  and  as  paramidophenol,  both  united  with  glyco-uronic  and  sul- 
phuric acids ;  in  rabbits,  chiefly  as  paramidophenol,  paired  with  the  acids.  It  is 
probable  that  the  proportion  of  antifebrin  which  is  decomposed  varies  with  the  size 
of  the  dose  and  the  condition  of  the  system. 

The  medical  virtues  of  antifebrin  were  first  discovered  by  Cahn  and 
Hepp,  and  have  been  abundantly  confirmed  by  numerous  observers. 
When  given  to  healthy  men  in  doses  of  seven  to  ten  grains  it  usually 
produces  no  appreciable  effect.  The  repetition  of  this  dose  may  cause 
somnolence,  constipation,  occasionally  headache  or  nausea,  malaise,  and 
a  peculiar  cyanotic  condition  of  the  face  and  extremities.  When  given 
to  persons  suffering  from  fever  in  doses  of  ten  grains  antifebrin  usually 
produces  in  about  an  hour  fall  of  temperature,  which  reaches  its  maxi- 
mum in  two  or  three  hours  and  may  continue  from  six  to  seven  hours. 
In  some  cases  at  this  time  the  cyanosis  is  apparent ;  usually,  but  not 
always,  the  fall  of  temperature  is  accompanied  by  a  profuse  sweating, 
which  is  generally  described  by  clinicians  as  being  less  than  that  produced 
by  corresponding  doses  of  antipyrin.  The  fall  of  temperature  is  not 
dependent  upon  sweating,  since  it  sometimes  occurs  without  the  sweating, 
and  G.  Pavai  Vajna  finds  that  the  sweating  can  be  arrested  in  great  part 
by  atropine  without  interfering  with  the  thermic  action  of  the  drug.  In 
rare  cases  the  lowering  of  the  bodily  temperature  has  been  coincident 
with  the  occurrence  of  collapse.  Occasionally  there  is  an  eruption  some- 
what similar  to  that  commonly  produced  by  antipyrin,  which  is  especially 
abundant  upon  the  face  and  forehead,  and  of  a  dark  red  color.  Some- 
times the  eruption  resembles  that  of  scarlatina,  and  there  may  be  much 

*  In  an  elaborate  research  on  various  drugs  of  the  aniline  group  (Dentsch.  Med. 
Wochensch.,  1895,  xxi.)  it  was  found  that  those  substances  which  produced  in  the  organ- 
ism paramidophenol  or  parace tamidophe nol  were  active,  whilst  those  which  made  ethyl- 
acelamidophenol  were  not  active. 

t  The  changes  which  occur  in  antifebrin  in  the  system  have  led  to  the  theory  that  its 
medical  virtues  are  dependent  upon  the  liberation  of  aniline  in  the  blood.  The  symptoms 
produced  by  antifebrin  are  certainly  similar  to  those  caused  by  aniline.  Thus,  Herczel 
states  that  in  a  case  of  aniline-poisoning  the  symptoms  were  colossal  cyanosis,  sweating, 
vomiting,  tinnitus  aurium,  dyspnoea,  fixedness  of  pupils,  disturbance  of  sensibility,  and 
a  temperature-fall  of  5.3°  C.,  accompanied  by  a  marked  decrease  in  the  coloring-matter 
of  the  blood  and  of  the  number  of  red  blood-corpuscles. 


612  GENERAL  REMEDIES. 

subdermal  swelling  (Armin  Hugher8).*  Mydriasis  and  deafness,  with 
ringing  in  the  ears,  have  been  noted  occasionally.  Collapse  appears  to 
be  less  frequent  than  with  antipyrin.  The  experiments  of  Hobart  A.  Hare 7 
show  that  at  present  inexplicable  cardiac  failure  may  occur  suddenly. 

In  the  experiments  of  Herczel,8  the  symptoms  produced  by  fifteen  to  twenty  grains 
in  rabbits  were  loss  of  the  reflexes,  tremors  deepening  into  periodic  convulsive  move- 
ments, great  fall  of  temperature,  frequent,  irregular,  superficial  respiration,  reten- 
tion of  urine,  coma,  and  general  paralysis,  ending,  if  the  dose  had  been  large 
•enough,  in  death,  which  could  not  be  prevented  by  artificial  respiration.  The  heart 
was  arrested  in  diastole.  After  the  prolonged  action  of  the  drug  there  was  fatty 
degeneration  of  the  heart,  liver,  and  kidneys.  Weill 9  noticed,  in  addition  to  these 
symptoms,  an  anaesthesia,  which  in  the  later  stages  of  the  poisoning  was  almost 
.complete. 

Nervous  System. — The  cause  of  the  convulsions  of  acetanilid-poison- 
ing  does  not  seem  to  have  been  determined.  The  coma  which  is  present 
in  the  advanced  stages  of  the  poisoning  indicates  that,  directly  or  indi- 
rectly, antifebrin  affects  the  cerebral  function,  but  consciousness  is  stated 
t>y  experimenters  to  be  preserved  at  a  time  when  the  lower  portion  of  the 
nervous  apparatus  is  distinctly  affected.  According  to  Bokai,10  antifebrin 
paralyzes  motor  nerve-endings  of  the  frog's  muscles  in  a  manner  similar 
to  curare,  and  when  brought  in  contact  with  the  muscle  itself  for  a  suf- 
ficient length  of  time  destroys  its  capability  of  contraction.  In  the  poi- 
soned animal,  however,  just  before  death  the  muscles  respond  actively, 
although  irritation  of  motor  nerve-trunks  fails  to  elicit  response. 

Circulation. — Usually  when  antifebrin  is  given  to  patients  with  fever 
there  is  a  fall  in  the  pulse-rate  corresponding  to  the  fall  of  temperature. 
The  size  of  the  pulse  is  also  reduced,  and  it  may  even  become  thready. 
Weill  has  found  that,  injected  into  the  frog,  the  drug  causes  at  first  an 
acceleration  of  the  heart' s  beat,  with  apparent  increase  in  the  force  of  the 
impulses,  followed  after  a  time  by  slowing  and  irregularity  of  contraction. 
In  the  earlier  stage  the  size  of  the  pulse-wave  is  increased  and  the  re- 
spiratory curve  is  more  accentuated  ;  later  the  pulse-oscillations  diminish 
and  become  irregular  and  quickened,  and  if  the  dose  has  been  large 
enough  the  manometric  writing  resembles  that  produced  by  asphyxia. 
In  the  earlier  stages  of  the  action  there  is  a  slight  rise  in  arterial  pressure. 

The  cyanosis  of  antifebrin-poisoning  has  been  thought  to  be  due  to 
the  formation  of  methaemoglobin  and  Stewart20  reports  two  cases  in 
which  the  blood  had  the  characteristic  chocolate  color,  although  no  spec- 
troscopic  examination  seems  to  have  been  made.  On  the  other  hand  in 
cases  of  poisoning  with  marked  cyanosis  both  Freund11  and  Stengel21 
were  unable  to  detect  anything  abnormal  in  the  blood  by  spectroscopical 
examination.  The  blood  changes  do  not  appear  to  be  characteristic  ; 
Stewart  reports  marked  reduction  of  the  number  of  red  cells  but  in  one 
of  Stengel's  cases  the  corpuscles  were  6,000,000.  Herczel  states  that 

*  See  also  Medical  News,  Ixxii.  791. 


ANTIPYRETICS.  613 

the  red  corpuscles  do  not  adhere  in  rouleaux,  that  they  are  somewhat 
granular,  and  that,  when  the  drug  is  given  to  dogs  for  a  length  of  time, 
the  blood  is  less  alkaline  than  normal,  and  contains  in  its  serum  dissolved 
coloring- matter.  According  to  Lepine  and  Aubert,12  the  oxygen  of  the 
blood  is  distinctly  decreased. 

Nutrition. — Kumagawa  found  that  while  small  doses  had  no  definite 
effect,  large  doses  enormously  increased  the  nitrogenous  elimination  ;  but 
in  Lepine' s  experiments  the  results  varied,  there  being  sometimes  an  in- 
crease and  sometimes  a  diminution,  while  H.  C.  Taylor13  obtained  a 
slight  increase  :  so  that  it  is  impossible  at  present  to  say  what  is  the  action 
of  the  drug  upon  protoplasmic  chemical  activity. 

According  to  Kumagawa,  antifebrin  exerts  a  strong  antiseptic  influ- 
ence upon  intestinal  changes,  decreasing  the  bacteria  in  the  intestines, 
and  the  urinary  indican. 

Temperature. — The  only  information  we  have  concerning  the  method 
by  which  acetanilid  lowers  bodily  temperature  is  furnished  by  the  experi- 
ments of  H.  A.  Hare  and  E.  M.  Evans.1*  It  is  not  sufficient  for  a  posi- 
tive conclusion,  but  indicates  that  in  fevered  animals  antifebrin  produces  a 
fall  of  the  temperature  by  decreasing  heat-production. 

In  fifteen  experiments  upon  normal  animals,  which  in  nearly  all  cases  were 
allowed  to  run  free,  Hare  obtained  a  distinct  fall  of  temperature  from  antifebrin, — 
a  result  confirmed  by  Evans,  but  not  in  accord  with  the  results  of  Cahn  and  Hepp, 
who  found  that  antifebrin  had  not  a  constant  influence  upon  the  temperature  of  the 
normal  animal.  Hare,  employing  the  calorimeter  of  H.  C.  Wood,  found  that  in 
the  normal  animal  heat-dissipation  and  heat-production  were  variously  affected,  in 
some  cases  being  notably  increased,  in  other  cases  notably  decreased,  arid  in  others 
not  distinctly  altered.  Evans,  employing  the  D'Arsonval  calorimeter,  also  reached 
various  results.  In  eleven  experiments  heat-dissipation  was  decreased  nine  times, 
while  heat-production  was  increased  four  times  and  decreased  five  times.  In  ex- 
amining the  records  of  the  calorimetric  experiments  made  by  Hare  and  Evans  on 
the  normal  animal,  we  find  that  not  only  did  the  rectal  temperature  not  fall  under  the 
influence  of  antifebrin,  but  in  nearly  every  instance  there  was  a  very  distinct  rise, 
amounting  in  some  cases  to  over  a  degree.  It  is  evident,  therefore,  that  these 
experiments  cannot  be  used  to  explain  how  antifebrin  reduces  temperature  when 
it  does  cause  a  fall.  The  attempt  to  reason  how  a  certain  result  is  produced 
by  a  remedy  from  experiments  in  which  that  result  was  not  produced  is  necessarily 
futile. 

In  Hare's  experiments  made  upon  dogs  in  which  fever  was  caused  by  the  injection 
of  pepsin,  antifebrin  failed  to  produce  any  constant  fall  of  the  bodily  temperature, 
probably  because  the  dose  was  not  large  enough.  In  the  calorimetric  studies  heat- 
production  was  usually  decreased,  but  sometimes  it  was  increased, — an  assertion 
which  is  also  true  of  heat-dissipation.  These  experiments  must  likewise  be  laid 
aside,  because  there  was  no  fall  of  temperature  caused  by  the  antifebrin.  In  Evans's 
experiments  with  fever  produced  by  the  injection  of  albumose,  the  antifebrin  nearly 
always  caused  a  distinct  reduction  of  temperature.  In  the  calorimetric  studies  the 
results  obtained  were  constant,  there  being  in  each  of  the  six  consecutive  experiments 
a  decrease  in  both  the  hourly  heat-dissipation  and  the  hourly  heat-production,  the 
amount  of  decrease  seemingly  bearing  some  relation  to  the  fall  of  temperature. 
Il  is  plain  that  a  decrease  of  heat-dissipation  would  have  a  natural  tendency  to  ele- 
vate bodily  temperature,  and  therefore  the  fall  of  temperature  must  have  been  due 
to  the  decrease  of  the  production,  which  in  turn  gave  rise  to  the  decrease  in  the 
heat-dissipation. 


614  GENERAL    REMEDIES. 

THERAPEUTICS. — The  therapeutic  use  of  antifebrin  is  exactly  parallel 
to  that  of  antipyrin.  Some  practitioners  prefer  it  on  the  ground  that  it  is 
less  liable  than  is  antipyrin  to  produce  collapse,  painful  skin  lesions,  or 
other  disagreeble  effects,  but  it  is  certainly  capable  of  causing  fatal  acute 
or  chronic  poisoning.  According  to  Sembritski 16  it  acts  very  badly  on 
pregnant  or  nursing  women.  Lepine  "  affirms  that  it  will  relieve  not  only 
the  fulgurant  pains  of  spinal  disease,  but  also  the  tremors  produced  by 
multiple  sclerosis,  and  is  often  useful  in  epilepsy.  Dose,  five  to  fifteen 
grains  (0.3-1  Gm.). 

Acetanilid  affords  a  useful  surgical  dressing,  and  has  the  superiority 
over  iodoform  of  being  free  from  odor,  and  perhaps  of  being  more  anal- 
gesic. It  is  frequently  employed  with  equal  amounts  of  boric  acid,  finely 
powdered,  in  the  treatment  of  minor  infected  wounds.  The  powder  may 
be  freely  used,  or  an  ointment  of  from  ten  to  forty  per  cent,  strength;  in 
vaginitis  or  urethritis  a  mixture  (twenty  to  forty  grains  to  one  fluid- 
ounce)  with  gum-arabic  water  may  be  injected.  The  free  external  use  is 
not  entirely  devoid  of  danger,  as  cases  have  been  reported  of  collapse 
with  intense  cyanosis  and  subnormal  temperature  produced  by  the  sur- 
gical use  of  the  drug.* 

Toxicology. — The  symptoms  of  acute  poisoning  by  antifebrin  are 
vomiting,  muscular  weakness,  cyanosis,  coldness  of  the  extremities,  sub- 
normal temperature,  profuse  sweating,  disturbances  of  respiration,  fixed 
dilated  pupils,  rapid  irregular  heart  action,  ending  in  collapse  and  cardiac 
death.  In  some  cases  an  impaired  consciousness  has  not  been  present 
until  very  late  in  the  poisoning ;  in  others  a  complete  unconsciousness  has 
been  a  comparatively  early  symptom.  The  urine  may  be  dark  owing,  it 
is  said,  to  haematoporphyrin  (methaemoglobin?).  Leucocytosis  with 
nucleation  of  the  red  blood-corpuscles  has  been  noted. 

Sixty  grains  of  it  are  asserted  to  have  caused  death,  but  have  been 
recovered  from  after  the  most  alarming  symptoms.  (See  Doll,  quoted  by 
Biach,  also  P.  Brown.18)  Marichaux15  details  a  case  in  which  four  grains 
caused  in  a  child  collapse,  with  complete  unconsciousness,  ending  in 
recovery. 

In  chronic  poisoning  the  most  pronounced  symptoms  are  anaemia  and 
cyanosis  ;  gastric  disturbance,  failure  of  the  general  nutrition,  rapid,  feeble 
heart  action,  and  distinct  enlargement,  without  tenderness,  of  the  spleen 
have  been  noticed.  There  is  not  only  great  decrease  in  the  number  of 
the  red  blood-corpuscles  and  in  the  percentage  of  haemoglobin,  but  also 
marked  increase  in  the  number  of  the  white  blood- cells,  with  nucleation 
of  the  red  blood-corpuscles  (see  Stengel  and  White19). 

ACETPHENETIDINUM.     U.  S. 
Acetphenetidin,  or  Phenacetin,  an  acetyl  derivative  of  para-amidophenol , 

*  See  Phila.  Polyclinic,  1897 ;  Atlantic  Med.  Weekly,  1898 ;  and  Med.  and  Surg. 
Rep.,  1897,  Ixxvi;  P.  M.  /.,  Sept.  1901. 


ANTIPYRETICS.  615 

crystallizes  in  tasteless,  colorless  needles,  slightly  soluble  in  water,  more 
so  in  alcohol.  Phenacetin  is  eliminated  by  the  kidneys,  probably  entirely 
altered,  phenetidin  appearing  in  the  urine.  According  to  Muller,1  this 
change  must  take  place  after  absorption,  since  both  the  gastric  and  pan- 
creatic secretions  are  without  effect  on  the  compound.  O.  Hinsberg  and 
A.  Kasta  have  found  that  when  given  to  dogs  in  doses  of  fifteen-hun- 
dredths  to  two-tenths  of  'a  gramme  per  kilo  phenacetin  has  no  effect,  but 
in  very  large  doses  it  causes  vomiting,  irregular  gait,  hurried  respiration, 
and  somnolence,  followed  by  general  cyanosis  and  discoloration  of  the 
blood,  due  to  the  formation  of  methaemoglobin. 

The  therapeutic  dose  of  phenacetin  produces  no  symptoms,  but  the 
toxic  dose  is  said  to  cause  violent  vomiting,  great  cyanosis,  chocolate- 
colored  urine,  yellow  discoloration  of  the  body,  leucocytosis,  and  death 
(Kronig).  Mahnert3  states  that  the  muscular  weakness  produced  by 
phenacetin  is  of  spinal  origin,  and  that  in  massive  doses  the  drug  is 
antagonistic  to  strychnine,  also  that  both  respiration  and  heart  are  para- 
lyzed by  it.  According  to  the  same  observer  it  is  chiefly  eliminated  un- 
changed ;  and  the  urine  gives  a  positive  Trommer's  reaction,  although 
containing  no  sugar.  Ledoux 4  asserts  that  in  doses  of  o.  5  gramme  per 
kilo  phenacetin  causes  a  fall  of  the  blood-pressure  ;  but  as  he  used  an  alco- 
holic solution  his  results  are  not  entirely  reliable.  H.  C.  Wood,  Jr. ,  and 
H.  B.  Wood 17  found  that  the  drug,  given  intravenously  suspended  in  water, 
had  absolutely  no  effect  on  blood-pressure.  Doses  of  o.  5  gramme  per  kilo 
killed  by  arrest  of  respiration  ;  which  can,  perhaps,  however,  be  attrib- 
uted to  the  mechanical  influence  of  undissolved  particles.  Frogs  allowed 
to  swim  in  a  saturated  aqueous  solution  of  phenacetin  in  four  hours  became 
totally  paralyzed,  the  motor  nerves  and  muscles  retaining  their  irritability. 
Ott 5  found  that  phenacetin  pronouncedly  decreases  heat-production  with- 
out producing  distinct  alteration  of  blood-pressure,  and,  therefore,  probably 
acts  as  an  antipyretic  by  lessening  the  heat-production  through  an  influence 
upon  the  nervous  system.  According  to  Falcone  and  Gioffredi 10  changes 
in  the  cerebral  cortical  cells  can  be  demonstrated  in  animals  killed  with 
phenacetin. 

THERAPEUTICS. — Phenacetin  has  been  largely  used  as  an  antipyretic, 
and  for  the  relief  of  pains  of  such  character  as  antipyrin  is  employed 
against.  Large  amounts  of  it  can  apparently  be  taken  without  serious 
result.  In  a  case  reported  to  us  by  E.  C.  Wagner,  one  hundred  and 
twenty  grains  were  taken  in  twelve  hours  without  the  production  of  any 
symptoms.  The  only  serious  case  of  poisoning  by  it  that  we  know  of  is 
that  reported  by  Hollopeter,6  in  which  a  woman  took  twenty-two  and  a 
half  grains  in  six  hours,  producing  collapse  with  marked  lividity,  great 
dyspnoea  and  restlessness,  cold  perspiration,  and  slightly  dilated  pupils, 
ending  in  recovery. 

There  can  be  no  doubt  of  the  efficiency  of  phenacetin,  and  it  would 
appear  that  it  more  rarely  produces  unpleasant  symptoms  than  antipyrin, 
though  urticaria  has  been  noticed  after  its  exhibition  (Mahnert).  If  the 


616  GENERAL  REMEDIES. 

statements  of  Crombie 7  and  of  Hirschfelder " — that  it  acts  more  gradually 
than  other  antipyretics,  and  that  its  influence  does  not  reach  its  maximum 
for  three  or  four  hours — be  correct,  phenacetin  is  probably  the  most  valu- 
able of  the  antipyretics,  especially  as  it  seems  to  be  the  least  poisonous. 
At  present  it  is  probably  the  most  used  of  its  class.  Dose,  from  ten  to 
twenty  grains  (0.65-1.3  Gm. ).  Phenacetin  is  highly  commended  by  M. 
H.  Lee9  as  a  local  antiseptic  dressing. 

PHENOCOLL  HYDROCHLORIDE. — Phenocoll  occurs  in  white  needle-like  crys- 
tals ;  it  is  made  by  the  action  of  glycocoll  upon  phenetidin.  Its  hydrochloride  is  a 
white,  finely  crystalline  powder,  very  soluble  in  water. 

Physiological  Action. — The  action  of  phenocoll  upon  the  animal  organism 
is  not  very  marked,  Von  Mering  having  found  that  twenty-three  grains  of  it  will  not 
produce  any  pronounced  symptoms  in  the  rabbit.  According  to  Isaac  Ott,  the 
toxic  dose  produces,  in  the  frog,  paralysis  of  both  the  motor  and  sensory  functions 
of  the  spinal  cord,  with  death  from  diastolic  arrest  of  the  heart ;  in  rabbits,  quietude, 
partial  paraplegia,  and  cyanosis,  with  acceleration  of  the  respiratory  movement  and 
depression  of  temperature  and  of  the  arterial  pressure.  David  Cerna  and  William 
S.  Carter  determined  that  the  influence  of  phenocoll  upon  the  circulation  is  exceed- 
ingly feeble.  The  fall  of  the  arterial  pressure  caused  by  enormous  doses  occurred 
after  section  of  the  spinal  cord  and  of  the  pneumogastrics  ;  so  that  it  must  be  con- 
cluded that  phenocoll,  when  in  sufficient  amount,  is  a  cardiac  depressant.  The 
action  of  smaller  doses  was  not  made  out.  The  pulse  was  found  by  Cerna  and 
Carter  to  be  primarily  decreased  by  inhibitory  stimulation,  then  increased  by  in- 
hibitory paralysis,  and  finally  diminished  by  direct  action  upon  the  heart. 

The  same  investigators  affirm  that  phenocoll  has  no  action  upon  the  blood,  but 
the  correctness  of  this  seems  to  be  challenged  by  the  cyanosis  which  has  been 
noted  both  in  man  and  in  rabbits.  In  experiments  made  upon  animals  with  fever, 
Cerna  and  Carter  found  that  the  fall  of  temperature  produced  by  phenocoll  is  due 
to  an  enormous  reduction  of  heat-production,  heat-dissipation  being  practically  not 
altered.  As  the  result  of  some  evidently  not  elaborate  chemical  studies,  P.  Balzer1 
states  that  phenocoll  very  distinctly  increases  the  nitrogenous  elimination  :  the  cor- 
rectness of  this  is  very  doubtful. 

Phenocoll  is  rapidly  absorbed  and  almost  as  rapidly  eliminated.  According  to 
Cohnheim,  it  may  be  detected  in  the  urine  from  one  to  nine  hours  after  its  inges- 
tion.  It  is  probably  in  part  oxidized  in  the  system,  since  the  urine  after  its  free 
administration  becomes  of  a  dark,  reddish-brown  color.  It  is  possible,  however, 
that  this  color  is  due  to  indican  and  biliary  substances,  both  of  which  have  been 
found  in  the  urine. 

THERAPEUTICS. — In  1891  Hertel  and  Herzog*  stated  that  phenocoll  rarely,  if 
ever,  produces  gastro-intestinal  irritation  or  other  disagreeable  symptoms,  that  its 
antipyretic  action  is  quick  and  never  accompanied  by  any  depression,  and  that 
the  free  sweating  which  is  apt  to  occur  with  it  may  readily  be  prevented  by  minute 
doses  of  atropine.  Both  Hertel  and  Herzog  assert  that  phenocoll  is  a  valuable 
remedy  in  acute  and  chronic  rheumatism.  The  first  reports  regarding  the  antipy- 
retic action  of  the  drug  have  received  wide  confirmation,  and  it  would  seem  that 
phenocoll  is  one  of  the  safest,  promptest,  and  most  efficient  members  of  its  class. 
On  the  other  hand,  it  has  been  stated  that  in  rheumatism  and  as  an  analgesic  in 
ataxic  or  other  nerve  pains  it  is  inferior  to  the  older  remedies.  These  results  may, 
however,  have  been  due  to  a  too  timid  use  of  the  phenocoll,  as  it  is  affirmed  by 
some  clinicians  that  five  grammes  or  seventy-seven  grains  of  it  are  usually  re- 
quired to  have  an  effect  in  rheumatism,  whilst  most  writers  give  the  dose  as  much 
smaller  than  this.  In  rare  instances  it  produces  vomiting,  but  we  have  met  with 
no  reports  of  human  poisoning  by  it.  The  ordinary  dosfe  may  be  set  down  as  twelve 
to  fifteen  grains  (0.78-1  Gm. ),  in  solution  or  capsule. 


ANTIPYRETICS.  '  617 

EXALGINE. — Methylacetanilid  occurs  in  needles  or  long  tablet-like  crystals, 
almost  insoluble  in  cold  water,  freely  soluble  in  hot  water.  When  given  to  man 
in  full,  non-poisonous  doses,  it  produces  slight  amblyopia  and  vertigo,  accom- 
panied in  some  persons  by  vomiting,  tinnitus  aurium,  headache,  drowsiness,  and 
vaso-motor  disturbances,  such  as  sweating.  After  large  doses  cyanosis  is  pro- 
nounced, but  no  eruption  upon  the  surface  of  the  skin  seems  as  yet  to  have  been 
noticed.  No  fatal  poisoning  by  it  has  been  reported,  but  in  a  case  of  A.  C.  Hart- 
ley's eighteen  grains  in  divided  doses  produced  a  general  motor  paralysis,  with 
dyspncea,  intense  pallor,  dilated  pupils,  and  pronounced  palpitation  of  the  heart. 
In  a  second  case,  two  doses  of  three  grains  each  produced  in  a  boy  fourteen  years 
old  a  sudden  almost  lethal  heart-failure,  with  dilated  pupils  and  dyspnoea.  In  a 
case  reported  by  Gillespie  there  were  violent  convulsions.* 

According  to  Brigonnet,  hypodermic  injections  of  exalgine  cause  in  the  lower 
animals  violent  epileptiform  convulsions,  profuse  salivation,  cyanosis,  disturbance 
of  breathing,  fall  of  temperature,  and  alteration  of  the  blood,  which  becomes  dark 
prune-colored  and  contains  an  abundance  of  methaemoglobin.  The  muscles  at  the 
seat  of  the  injection  are  said  to  be  locally  paralyzed,  and  although  small  doses 
increase  slightly  the  blood-pressure,  after  the  toxic  dose  the  pressure  suddenly  falls. 
The  urine  does  not  become  albuminous  nor  bloody. 

Exalgine  has  been  used  as  an  antipyretic,  but  to  a  very  much  larger  extent  as 
an  analgesic,  and  is  said  also  to  be  useful  in  chorea  and  polyuria.  According  to 
Moncorvo,  as  an  analgesic  it  has  at  least  five  times  the  power  of  antipyrin.  Dose, 
three  to  six  grains  (0.2-0.4  Gm. ),  not  more  than  twelve  grains  being  exhibited  in 
the  twenty-four  hours.  Moncorvo  gives  the  dose  for  a  child  five  years  old  as  one 
and  a  half  grains  (0.09  Gm. ). 

SALIPVRIN. — Antipyrin  Salicylate  is  a  white,  coarsely  crystalline,  odorless, 
slightly  sweetish  powder,  readily  soluble  in  alcohol.  It  is  commended  by  Guttman 
and  Kollmann  as  an  active  antipyretic  and  anti rheumatic,  which  rarely  produces 
toxic  symptoms,  although  an  eruption  resembling  that  of  antipyrin  has  been  noted; 
the  color  of  the  urine  is  not  affected,  but  tests  show  the  presence  of  a  salicylate. 
Kollmann  states  that  it  sometimes  vomits,  and  that  the  daily  dose  should  never 
exceed  forty-five  grains  (2.9  Gm. ),  and  should  always  be  less  than  this  in  the  be- 
ginning, as  some  individuals  are  intolerant  of  it.  Salipyrin  has  been  used  to  a  con- 
siderable extent  in  all  forms  of  rheumatism,  in  influenza,  in  various  fevers,  in 
migraine,  and  in  the  whole  class  of  diseases  in  which  its  component  constituents 
have  been  found  to  be  useful  ;  also  locally  in  coryza.  The  usual  dose  is  from 
seven  to  fifteen  grains  (0.45-1  Gm. ),  in  capsule  or  tablet,  repeated  every  three  or 
four  hours,  but  some  clinicians  prefer  a  single  large  dose  of  forty-five  grains 
(2.9  Gm. ). 

PYRAMIDON. — Dimethylamidophenyl-dimethylpyrazolon. — This  is  a  yellowish- 
white,  crystalline,  almost  tasteless  powder,  soluble  in  ten  per  cent,  of  water.  It 
was  introduced  by  Filehne J  as  a  remedy  having  an  action  similar  to  that  of  antipyrin. 
It  appears  to  be  absorbed  readily,  and,  according  to  M.  Jaffe,2  is  in  part  eliminated 
unchanged  in  the  urine,  in  part  converted  into  the  red  substance,  rubaronic  acid, 
and  in  part  changed  into  a  substance  which  is  colored  deep-blue  by  ferric  chloride, 
and  is,  probably,  antipyrylurea.  Its  general  physiological  activities  have  not  been 
worked  out,  but  G.  Ssadkowski  f  is  said  to  have  experimentally  determined  that  it 
has  a  powerful  action  upon  the  heart  and  blood-vessels,  increasing  the  arterial  ten- 

*See  also  Bull,  de  Therap.,  March,  1891 ;  and  Brit.  Med.  Journ.,  Feb.  1890. 
t  Ssadkowski  (Russkij  Wratsch,  1902,  No.  18.)    We  have  not  seen  the  original  paper, 
nor  yet  a  satisfactory  abstract. 


6i8 


GENERAL    REMEDIES. 


sion,  so  that  in  cases  of  tuberculosis  of  the  lungs  with  already  heightened  arterial 
pressure,  it  may  produce  haemoptysis,  and  is,  therefore,  contra-indicated. 

Pyramidon  has  been  used  to  a  considerable  extent  as  an  antipyretic  and  as  an 
analgesic.  The  reports  as  to  its  value  as  an  antipyretic  in  typhoid  and  other  low 
fevers  are  somewhat  contradictory,  various  clinicians  having  expressed  strong  sen- 
timents in  its  favor,  claiming  that  though  it  acts  more  slowly  its  influence  continues 
much  longer  than  does  that  of  the  older  antipyretics.  Other  observers  assert  that  it 
is  more  prone  than  are  antipyrin  and  phenacetin  to  produce  excessive  sweating  and 
collapse.  It  has  been  especially  praised  in  migraine,  neuralgia,  and  all  the  pains 
of  the  character  for  which  phenacetin  and  antipyrin  have  been  previously  used. 
According  to  Roth,  pyramidon  is  a  useful  drug  in  acute  rheumatism,  though  of 
little  value  in  chronic  cases.  Albrecht  has  found  it  of  value  in  asthma.  The  dose 
is  twelve  grains  dissolved  in  water  or  taken  in  capsules,  and  may,  when  it  is  neces- 
sary, be  repeated  up  to  thirty-six  grains  in  the  twenty-four  hours. 

Three  compounds  of  pyramidon  have  been  put  upon  the  market,  the  camphor- 
ate,  the  bicamphorate,  and  the  salicylate.  It  is  affirmed  that  the  presence  of 
camphoric  acid  markedly  lessens  the  tendency  of  pyramidon  to  produce  sweating 
without  interfering  with  its  antipyretic  action.  In  the  bicamphorate  the  anhydrotic 
influence  is  so  great  that  the  drug  has  been  strongly  recommended  in  the  night 
sweats  in  phthisis. 

Pyramidon  salicylate  appears  to  be  inferior  in  the  treatment  of  rheumatism  to 
the  older  salicylates,  though  it  may  be  employed  in  subacute  and  chronic  cases  in 
times  of  excessive  pain.  The  dose  of  any  one  of  these  preparations  is  seven  and  a 
half  to  twelve  grains  (0.5-0.75  Gm. ),  repeated  as  necessary.  In  tuberculosis, 
with  excessive  sweating,  it  is  advised  to  give  two  doses  a  day  of  eight  grains  each. 

THERMOL.  Acetyl-salicyl-phenetidin. — This  substance  is  a  white,  crystalline, 
odorless,  tasteless  powder,  which  is  affirmed  to  be  a  harmless  and  active  antipyretic 
and  analgesic,  and  as  such  has  been  used  to  a  considerable  extent  in  the  treatment 
of  typhoid  fever,  neuralgia,  dysmenorrhcea,  migraine,  etc. ;  also  as  an  antispasmodic 
in  whooping-cough.  Dose,  three  to  fifteen  grains. 

PYROSAL.  Antipyrin  salicyl-acetate. — PHENOSOL.  Salicyl-acetic-acid-phenet- 
idide. — These  compounds,  which  have  been  proposed  and  to  some  extent  used  as 
antirheumatics  and  antineuralgics,  are  asserted  to  be  broken  up  into  their  con- 
stituents in  the  alimentary  canal  and  to  exert  the  influence  of  these  constituents 
upon  the  human  system.  Pyrosal  is  said  to  contain  about  fifty  per  cent,  of  anti- 
pyrin and  about  thirty-six  per  cent,  of  salicylic  acid  ;  phenosol  about  fifty-seven 
per  cent,  of  phenacetin  and  forty-three  per  cent,  of  salicylic  acid.  They  have  been 
given  in  doses  of  seven  grains  (0.5  Gm. )  from  two  to  six  times  in  the  twenty-four 
hours  (see  D.  M.  W.,  1898). 


REFERENCES. 


SALICYLIC   ACID. 


1.  DRASCHE    .   .   .  .  Cb.  C.,  1876. 

2.  SALKOWSKI    .   .  .  B.  K.  W.,  1875,  297. 

3.  BINZ Pract.,  xxvi.  443. 

4.  KOHLER C.  M.  W.,  1876,  553. 

5.  FARSKY Sb.  G.  W.,  Ixxiv.  ii. 

6.  FLEISCHKR    .  .   .  Med.  Centralb.,  1876,  628 

7.  Mosso A.  E.  P.  P.,  xxvi. 

8.  MUSSY B.  G.  T.,  xiii.  318. 

9.  BALZ A.  Hk.,  xviii.  60. 

10.  BYANOW Cb.  C.,  1877,  809. 

11.  STUART Pract.,  xviii.  425. 

12.  WOLFBERG    .   .   .  D.  A.  K.  M.,  xv.  403. 

13.  ROBIN L.  M.  R.,  1877,  151. 


14.  SEE B.  A.  M.,  1877,  697. 

15.  REISS B.  K.  W.,  1875,674. 

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17.  KRUEG Wien.   Med.   Presse,   1886, 

xxvii.  405. 

18.  GIBSON  and  FELKIN  .  Pract.,  1889,  xlii. 

19.  LABORDE    ...  .  B.  G.  T.,  xciii.  276. 

20.  DANEWSKV    .   .   .  Arb.  d.  Pharm.  Lab.  Mos- 

kau,  i.  190. 

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24.  FAVAL Thesis,  Lyon,  1887. 

25.  HAIC M.  C.  Tr.,  1888,  Ixxi. 


ANTIPYRETICS. 


619 


REFER  ENCES. —  Continued. 


32. 


WOLFSOHN    .   .   .  C.  M.  VV.,  1877,  30. 

VIRCHOW    .   .   .  .  Z.  P.  C.,  vi. 

SALOME Med.  Jahrb.  Aerzte  Wien, 

1885.  iv. 

KUMAGAWA   .   .   .  V.  A.  P.  A.,  1888,  cxiii. 
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1896,  xvii. 
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Ixii.  242. 
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GEDL C.  M.  W.,  1876,  403. 

NORTH Pract.,  xxiii.  184. 

JUSTI Cb.  C.,  1876,629. 

EWALD Pract.,  xvi.  200. 

HARK T.  G.,  iii.  450. 

BUTT L.  M.  R.,  1876,  193. 

STRICKER  .  .  .   .  B.  K.  W.,  1879,  xiii. 

HUBER T.  G.,  1887. 

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xii. 

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Soc.,  Boston,  1887. 

JUVET N.  Y.  Med.  Gaz.,  1867. 

GALLAHER.   .  .  .  Phila.  Med.  Exam.,  1852. 
WOOD  and  HARE  .  T.  G.,  1886,  73. 
LINOSSIER  and  LANNOIS  .  B.  G.  T.,  1896. 


WIECHOWSKI    .  .  A.  E.  P.  P.,  1902,  xlviii. 
GOODBODY  .  .   .  .  J.  P.,  xxv. 
MOREIGNE     ...  A.  M.  Ex.,  1900,  xii. 
A.  of  Op.,  1890,  xxv. 
,7.  GIFFORD     ....  A.   O.   R.,   1902,  xi. ;   also 

Tr.  A.  O.  S.,  1899. 
58.  FROMAGET  and  LAFFE  .  Ann.  O.,  1897,  cxviii. 

GLYCOSAL. 

i.  BLOCK T.  M.,  Sept.  1903. 

AMYLII   SALICYLAS. 
i.  LYONNET    .   .   .  .  R.  T.,  Ixviii. 
ASPIRIN. 

1.  SINGER A.  G.  P.,  1900,  Ixxxiv. 

2.  LIESAN D.  M.  W.,  1900,  xxvi. 

SALICIN. 

I.  HUSEMANN    .   .   .  Pflanzenstoffe,  903. 
a.  SCARPETTI     .  .   .  Rif.  M.,  1898,  805. 

3.  MACLAGAN     .  .  .  L.  L.,  1876,  i. 

ANTIPYRIN. 

1.  FILEHNE Z.  K.  M.,  1884,  vii.  641. 

2.  SAINT  HILAIRE   .Journ.    Laryngol.,    Otol., 

etc.,  1892. 

3.  HAGK Robert's  Jahresb.,  1885. 

4.  PINZANI Centralb.  f.  d.ges.  Therap., 

Aug.  1890. 

5.  FIEUX S.  Jb.,  cclvii. 

6.  FERRET  and  GIVRE  .  Le   Bull.  Med.,  Aug. 

1891. 

7.  MARAGLIANO    .   .  Kobert's  Jahresb.,  1885. 

8.  CAPITAN  and  GLEY  .  C.  R.  S.  B.,  1887,  iv. 


9.  IWANOFF     ....  A.  G.  P.,  1887,  Suppl. 

10.  SPITZ Th.  M.,  1887. 

11.  BRIGGS L.  M.  R.,  March,  1891. 

12.  SPITZER Centralb.      fur     Therap., 

1890,  viii. 
IV  ARDUIN Thesis,  Paris,  1885. 

14.  DEMME Fort.  M.,  1884,  ii.  657. 

15.  COPPOLA     .   .   .  .  Kobert's  Jahresb.,  1885,314. 

16.  SIMON  and  HOCK  .  Johns    Hopkins    Hosp. 

Bull.,  1890. 

17.  BLUMENEAU  ...  St.  Petersb.  Med.  Woch.. 

1887. 

18.  BATTEN  and  BOKENHAM  .  B.  M.  J.,  1889,  i. 

19.  CHOUPPE    ....  Sem.  M£d.,  July,  1887. 

20.  LEPINE Lyon  M.,  liii. 

21.  DEVRAUX-ARMAND  .  Thesis,  Nancy,  1885. 

22.  CASIMIR Thesis,  Lyons,  1886. 

23.  CERNA  and  CARTER  .  New  Remedies,  1892. 

24.  FAVAL Thesis,  Lyons,  1887. 

25.  BIACH Die  Neuren  Antipyretica. 

26.  CROLAsand  HAGOUMENG  .  Lyon  M.,  1889. 

27.  WOOD,  REICHERT,  and  HARE  .  T.  G.,  ii.  803. 

28.  DESTREE    ....  Journ.   de   M6d.   Clin.  de 

Pharm.,  1888,  Ixxxvi. 

29.  MARTIN Ott's  Modern  Antipyretics, 

1891. 

30.  GOTTLIEB  .  .   .  .  A.  E.  P.  P.,  1889,  xxvii. 

31.  GIRARD R.  M.  S.  R.,  1887,  vii. 

32.  GOTTLIEB  .  .  .   .  C.  M.  W.,  1888. 

33.  CHITTENDEN  and  CUMMINS  .  S.  L.  P.  C.  Y.,  ii. 

34.  UMBACH A.  E.  P.  P.,  xxi. 

35.  CAZENEUVE  and  VISBECK  .  Lyon  M.,  1892. 

36.  Roux  and  RODET  .  Lyon  M.,  1892. 

37.  VON  NOORDEN    .  B.  K.  W.,  1884,  523. 

38.  PRIBRAM Prager  Med.  Woch.,  1884. 

39.  SONNENBERGER   .  Th.  M.,  1888,  ii. 

40.  FEENY L.  L.,  1889. 

41.  CLEMENT    ....  Lyon  M.,  1891. 

42.  SAINT-PHILLIPPE  .  Journ.  de  M«5d.  de    Bor 

deaux,  1891. 

43.  GUIBERT Sem.  M6d.,  1891. 

44.  VERNEUIL  ....  Sem.  M£d.,  1891. 

45.  YOUNG N.  Y.  M.  R.,  1890. 

46.  SCHVVABE    ....  Deutsche  Med.  Zeit.,  1890 

47.  BARRS L.  L.,  Feb.  28,  1885. 

48.  LAWROW     ....  Z.  P.  C.,  1901,  xxxii. 

ACETOPYRIN. 

i.  BRAUN W.  K.  W.,  1900,  No.  39. 

a.  MEITNER    ....  St.  P.  M.  W.,  1900,  xx. 

EUPYRINE. 

1.  OVERLACH  ....  C.  I.  M.,  1900. 

2.  PORGES W.  M.  Bl.,  1901. 

ACETANILID. 

1.  FROTHINGHAM  and  PRATT  .  A.  J.  M.  S.,  1895, 

ex. 

2.  CAHN  and  HEPP  .  Prog.  M.,  Jan.  1887. 

3.  PAVAI  VAJNA    .  .Ceritralbl.    fur     ges. 

Therap.,  1887. 

4.  KUMAGAWA   .  .  .  V.  A.  P.  A.,  1888,  cxiii. 
J.  JAFFE  and  HILBERT  .  Z.  P.  C.,  1887-88,  xii. 

6.  HUGHER     .   .   .   .  C.  B.  S.  A.,  1887,  xvii. 

7.  HARE T.  G.,  1887. 

8.  HERCZEL    .  .  .  .  W.  M.  W.,  1887,  730. 

9.  WEILL B.  G.  T.,  cxii.  150;  Thesis, 

Paris,  1887. 

10.  BOKAI D.  M.  W.,  Oct.  1887. 

n.  FREUND D.  M.  W.,  1888,  xiv. 


62O 


GENERAL  REMEDIES. 


REFERENCES.—  Continued. 
12.  LEPINE  and  AUBERT  .  Gaz.   M£d.   de  Stras-        4 


bourg,  1887,  i. 

13.  TAYLOR S.  L.  P.  C.  Y.,  Jan.  1889. 

14.  EVANS T.  G.,  1887. 

15.  MARICHAUX  .   .   .  D.  M.  W.,  1889,  xv. 

16.  SEMBRITZKI  .   .   .  Th.  M.,  1889,  iii. 

17.  LEPINE Lyons  M.,  1886,  xlvi. 

18.  BROWN A.  J.  M.,  Dec.  1901. 

19.  STENGEL  and  WHITE  .  U.  P.  M.  B.,  1903. 

20.  STEWART  .   .   .   .  J.  A.  M.  A.,  1905,  xliv.  1725. 

21.  STENGEL  .   .   .   .  J.  A.  M.  A.,  xlv.  243. 

ACETPHENET1DINUM. 

1.  MULLER B.  K.  W.,  1888,  613. 

2.  HINSBERG     and     KAST  .  Centralb.     f.     ges. 

Therap.,  April,  1887. 

3.  MAHNERT  .  .   .  .  D.  M.  W.,  :888,  xiv. 


LEDOUX Rev.  de  Med.,  Paris,  1892, 

xii. 

5.  OTT J.  N.  M.  D.,  1888,  xv. 

6.  HOLLOPETER    .   .  M.  News,  1889. 

7.  CROMBIE     ....  Pract.,  1889,  xliii. 

8.  HIRSCHFELDER    .  D.  A.  K.  M.,  1888-89,  *l»v. 

9.  LEE Memphis   Med.    Monthly, 

1892,  xii. 

10.  FALCONE  and  GIOFFREDI  .  A.  I.  B.,  xxxiv. 

11.  WOOD,  JR.,  and  WOOD  .  U.  M.  M.,  July,  190x3. 

PHENOCOLL. 

1.  BALZER Th.  M.,  1892. 

2.  HERTEL  and  HERZOG  .  D.  M.  W.,  1891. 

PYRAMIDON. 

1.  FILEHNK     .   .   .   .  B.  K.  W.,  1896. 

2.  JAFFE I.  B.  I.  M.,  1902. 


CLASS  II.— LOCAL  REMEDIES. 


FAMILY  I.— STOMACHICS. 

STOMACHICS  are  drugs  which  especially  affect  the  mucous  membrane 
and  other  coats  of  the  gastro-intestinal  tract  so  as  to  increase  functional 
activity.  A  simple  bitter  is  a  substance  of  vegetable  origin  and  of  a  bitter 
taste,  which  has  no  influence  upon  the«general  system,  but  markedly  affects 
the  stomach  as  a  stimulant.  Borissow  u  found  that  the  introduction  of 
tincture  of  gentian  into  the  mouth  in  conjunction  with  the  presentation  of 
food  produced  a  greater  flow  of  gastric  secretion  than  did  the  food  alone. 
He  believes  that  this  action  is  a  reflex  one,  depending  on  the  bitter  taste. 
Simple  bitters  probably  influence,  however,  not  only  the  peptic  glands 
but  also  the  muscular  fibres,  since  Paul  Terray J  found  that  the  movements 
of  the  excised  stomachs  of  dogs,  kept  in  a  warm  salt  solution,  were  in- 
creased in  the  order  of  naming  by  extract  of  gentian,  cetrarin,  condurangin, 
extract  of  taraxacum,  quinine,  and  extract  of  quassia.  Cetrarin  was 
remarkable  for  its  influence  upon  the  intestinal  movements.  Although 
simple  bitters  may,  by  increasing  the  amount  of  food  taken,  affect  the 
general  nutrition  of  the  body,  they  are  essentially  locally  acting  drugs. 
Probably  all  bitter  vegetable  substances  are  stimulants  to  the  gastric  mucous 
membrane,  but  in  many  of  them,  as  in  morphine  and  strychnine,  such 
power  is  overshadowed  by  other  inherent  properties.  Some  of  these 
active  bitter  vegetable  substances  are  indeed  employed  on  account  of 
their  influence  upon  the  alimentary  tract,  notably  quinine  and  strychnine, 
but  in  others  of  them,  like  morphine,  the  local  is  entirely  swallowed  up 
in  the  general  influence.  By  virtue  of  their  irritant  action  the  simple 
bitters  produce,  when  in  overdoses,  nausea,  and  may  even  cause  active 
irritation  of  the  gastro-mucous  membrane.  They  have  also  some  tendency 
to  affect  the  bowels.  They  are  essentially  irritant,  and  are  contra-indi- 
cated by  inflammation  or  over-sensitiveness  of  the  alimentary  mucous  mem- 
brane. They  are  especially  indicated  by  loss  of  appetite,  when  such  loss 
of  appetite  is  the  outcome  of  a  depressed  condition  of  the  stomach,  but  when 
it  is  the  result  of  gastro-inflammation  they  will  do  harm.  A  second  class 
of  stomachics  are  the  so-called  dramatics,  which  depend  for  their  activity 
upon  the  presence  of  a  volatile  oil.  They  differ  from  the  simple  bitters 
in  being  more  powerful  but  less  permanent  as  local  stimulants.  (See 
page  623.)  A  third  class  of  drugs  contain  both  volatile  oil  and  bitter 
principle,  and  unite  the  properties  of  the  aromatics  with  those  of  the 
simple  bitters.  These  are  the  so-called  aromatic  bitters. 

621 


622  LOCAL   REMEDIES. 

SIMPLE   BITTERS. 

QUASSIA.     U.S. 

The  wood  of  Picraena  excelsa,  a  large  tree,  native  of  Jamaica.  This 
wood  is  light  both  in  density  and  color,  somewhat  resembling  that  of  the 
tulip-tree,  but  distinguished  by  its  intensely  bitter  taste.  It  is  kept  in 
the  shops  in  billets  and  in  raspings.  The  active  principle  is  Quassin,  an 
intensely  bitter,  neutral,  crystalline  principle.  Simaruba,  the  bark  of  the 
root  of  Simaruba  officinalis,  also  contains  quassin,  and  may  be  substituted 
for  quassia. 

PHYSIOLOGICAL  ACTION. — Quassia  can  hardly  be  said  to  be  poison- 
ous to  man,  the  largest  doses  producing  in  the  adult  only  gastric  irrita- 
tion, but  F.  Venn*  has  reported  a  case  in  which  in  a  young  child  the 
injection  into  the  rectum  of  a  decoction  representing  two  ounces  of  quassia 
was  followed  almost  immediately  by  vomiting,  stupor,  relaxation,  and 
collapse,  ending  in  death.  According  to  I.  Hoppe,"  quassin,  when  given 
to  frogs  in  doses  of  one  grain,  will  produce  weakness,  convulsions,  respira- 
tory and  cardiac  failure,  ending  in  death.  Locally,  quassin  is  a  distinct 
irritant.  In  man,  five  milligrammes  of  the  pure  crystalline  form  notably 
increased  the  secretion  of  bile  and  of  urine,  and  caused  some  looseness 
of  the  bowels  and  stimulation  of  the  bladder  ;  whilst  fifteen  milligrammes 
produced  violent  frontal  headache,  burning  pains  in  the  oesophagus  and 
throat,  nausea,  vomiting,  vertigo,  excessive  nervous  restlessness,  diar- 
rhoea, and  very  frequent  micturition,  but  diminished  renal  secretion.4 

THERAPEUTICS. — Quassia  is  probably  the  most  active  of  all  the 
simple  bitters,  and  may  be  used  whenever  such  remedies  are  indicated. 
In  cases  of  seat-worms  in  children,  a  strong  infusion  of  quassia  (two 
ounces  to  one  pint)  affords  a  most  harmless  and  efficient  injection.  Its 
exhibition  should  be  preceded  by  an  enema  of  simple  water,  after  a 
stool,  so  as  thoroughly  to  wash  out  the  rectum  and  allow  access  to  every 
fold  of  the  rectal  mucous  membrane.  The  official  preparations  are  a  tinc- 
ture (TINCTURA  QUASSIA — twenty  per  cent.,  U.  S. ),  dose,  twenty  drops 
to  a  teaspoonful  (1.2-4  C.c. );  an  extract  (EXTRACTUM  QUASSI^E,  U.  S.), 
dose,  one  to  three  grains  (0.06-0.19  Gm. )  ;  and  a  fluid  extract  (FLUID- 
EXTRACTUM  QUASSIA),  dose,  five  to  ten  drops  (0.3-0.6  C.c.). 

GENTIANA— GENTIAN.     U.  S. 

The  root  of  Gentiana  lutea,  or  the  yellow  gentian  of  the  Alps.  This 
root  occurs  in  the  shops  either  in  pieces  of  various  sizes  and  shapes,  but 
usually  several  inches  in  length,  or  else  in  transverse  slices.  The 
texture  is  spongy,  the  odor  faint  but  peculiar,  and  the  taste  bitter.  It 
contains  gentisic  acid,  which  was  discovered  by  Leconte  and  is  tasteless 
and  physiologically  inert.  The  active  principle  is  probably  the  gentio- 
pikrin  of  Kromayer,  a  neutral,  crystalline  substance,  of  an  intensely 
bitter  taste. 


STOMACHICS.  623 

THERAPEUTICS. — Gentian  is  one  of  the  most  efficient  of  the  simple 
bitters,  and  may  be  used  whenever  such  a  remedy  is  indicated.  It  is 
never  given  in  substance,  but  in  one  of  its  preparations.  These  are  the 
compound  tincture  (TINCTURA  GENTIAN^E  COMPOSITA — ten  per  cent, 
U.  S. ),  which  contains  gentian,  bitter  orange  peel,  and  cardamom,  dose, 
one  fluidrachm  to  half  a  fluidounce  (4-15  C.c. );  the  watery  extract 
(EXTRACTUM  GENTIANS,  U.  S. ),  dose,  two  to  four  grains  (0.13-0.26 
Gm.);  and  the  fluid  extract  (FUIDEXTRACTUM  GENTIANS,  U.  S. ),  dose, 
ten  minims  to  half  a  fluidrachm  (0.6-2  C.c.).  The  compound  infusion, 
formerly  official,  was  a  valuable  preparation,  containing  some  alcohol, 
and  much  used  in  doses  of  one  to  two  fluidounces  (30-60  C.c.). 

CALUMBA— COLUMBO.     U.  S. 

The  root  of  Jateorhiza  palmata,  a  climbing  vine  of  Mozambique.  It 
occurs  in  the  shops  in  transverse  disk-like  slices,  oval  or  circular  in  out- 
line, one  or  two  inches  in  diameter,  of  a  spongy  texture,  having  a 
yellowish  surface,  a  very  bitter  taste,  and  a  slightly  aromatic  odor.  It 
contains  a  great  deal  of  starch,  besides  berberine,  and,  it  is  said,  in  lesser 
amount,  columbin,  a  bitter  neutral  principle  crystallizing  in  rhomboid 
prisms  or  needles.  F.  Roux 5  has  found  that  columbin  given  to  pigeons 
in  doses  of  ten  centigrammes  produces  death,  preceded  by  failure  of  the 
appetite,  marked  signs  of  gastro-intestinal  irritation,  and  jaundice. 

THERAPEUTICS. — A  bitter,  slightly  aromatic  tonic,  useful  as  a  sto- 
machic in  cases  in  which  a  simple  bitter  is  indicated.  It  is  not  used  in 
substance.  Its  preparations  are — a  tincture  (TiNCTURA  CALUMB^E — ten 
per  cent.  >  U.  S. ),  dose,  one  to  two  fluidrachms  (4-7  C.c.),  and  a  fluid 
extract  (FLUIDEXTRACTUM  CALUMBA,  U.  S. ),  dose,  fifteen  minims  to 
half  a  fluidrachm  (1-2  C.c.). 

CHIRATA,  U.  S. ,  the  herb  and  root  of  Swertia  chirata,  a  plant  grow- 
ing in  the  northern  part  of  India,  is  one  of  the  best  of  the  simple  bitters, 
and  is  believed  by  some  to  exert  a  peculiar  influence  over  the  liver. 
Whenever  a  simple  bitter  is  indicated,  this  drug  may  be  employed,  espe- 
cially if  a  cholagogue  action  be  desired.  The  solid  extract  is  an  excellent 
preparation  in  doses  of  one  to  two  grains  (0.06-0.12  Gm. );  dose  of  the 
fluid  extract  (FLUIDEXTRACTUM  CHIRATA,  U.  S. ),  five  to  ten  minims 
(0.3-0.6  C.c. );  of  the  tincture  (TINCTURA  CHIRAT^E — ten  per  cent., 
U.  S.),  a  fluidrachm  (4  C.c.). 

BERBERIS,  U.  S.  Barberry. — The  root  and  berries  of  the  Berberis 
vulgaris  of  Europe  have  long  been  used  abroad  as  a  simple  laxative 
tonic,  and  the  U.  S.  Pharmacopoeia  recognizes  the  rhizome  and  roots  of 
B.  Aquifolium  and  other  species.  These  plants  depend  for  their  slight 
medical  activity  upon  the  presence  of  berberine  (see  Hydrastis)  and 
other  feeble  alkaloids.  They  have  been  used  in  atonic  dyspepsia,  espe- 
cially when  attended  with  hepatic  torpor  ;  and  also  as  alteratives  in  con- 


624  LOCAL   REMEDIES. 

stitutional  syphilis.     Dose  of  the  fluid  extract  (FLUIDEXTRACTUM  BER- 
BERIDIS,  U.  S. ),  thirty  minims  (2  C.c. ). 

PRUNUS   VIRGINIANA— WILD    CHERRY.     U.  S. 

Wild  cherry  bark  is  the  product  of  Prunus  (Cerasus)  serotina  or 
wild  cherry  tree,  not  of  Prunus  Virginiana  or  choke-cherry,  whose  name 
it  bears.  It  occurs  in  pieces  of  various  sizes,  usually  without  epidermis. 
The  color  is  a  reddish  cinnamon  ;  the  taste  slightly  astringent,  bitter,  and 
peculiar,  resembling  that  of  peach-leaves.  It  contains  tannic  acid,  bitter 
extractive,  a  nitrogenous,  crystallizable,  odorless  glucoside  (^Amygdalin), 
and  an  albuminous  principle  (^Emulsin).  When  amygdalin  in  watery 
solution  is  brought  in  contact  with  emulsin,  it  is  decomposed,  forming 
prussic  and  formic  acids  and  a  colorless,  thin,  volatile  oil,  which,  when 
pure,  has  a  peculiar,  agreeable  odor  and  a  burning  taste.  According  to 
Liebig  and  Wohler,6  seventeen  grains  of  amygdalin  yield  one  of  hydro- 
cyanic acid  :  therefore,  if  thirty-four  grains  of  amygdalin  be  mixed  with 
sixty-six  grains  of  an  emulsion  of  sweet  almonds,  a  two  per  cent,  (by 
weight)  solution  of  hydrocyanic  acid  will  be  formed. 

PHYSIOLOGICAL  ACTION. — Amygdalin  is  physiologically  inert,  as 
much  as  sixty  grains  having  been  taken  without  result.  Fifteen  grains 
may  cause  death  in  the  rabbit,  but  this  is  owing  to  its  being  converted 
into  prussic  acid  by  the  emulsin  contained  in  the  green  herbage  in  the 
stomach  of  the  rabbit.* 

THERAPEUTICS. — In  wild  cherry  bark  properly  administered  there 
are  three  active  ingredients, — tannic  acid,  bitter  extractive,  and  prussic 
acid.  The  amount  of  prussic  acid  is  too  small  to  cause  perceptible 
effects,  so  that  wild  cherry  bark  is  simply  a  feeble  astringent  and  tonic. 
It  has  been  very  largely  used  in  phthisis,  and  has  been  supposed  not 
only  to  act  as  a  tonic  and  astringent,  but  also  to  exert  a  calmative  influ- 
ence on  the  nervous  system. 

The  dose  of  the  infusion  (!NFUSUM  PRUNI  VIRGINIANS — four  per 
cent.,  U.  S. )  is  one  to  two  wineglassfuls  (60-118  C.c.).  The  syrup 
(SYRUPUS  PRUNI  VIRGINIANS — fifteen  per  cent,  U.  S. )  is  practically 
inert,  but  is  often  employed  as  a  vehicle.  The  dose  of  the  fluid  extract 
(FLUIDEXTRACTUM  PRUNI  VIRGINIANS,  U.  S. )  is  from  one-half  a 
fluidrachm  to  a  drachm  (2-4  C.c.). 

OREXIN. — Phenyldihydrochinazoline  Hydrochlorate ,  or  Orexcz  Hydrochlorate. 
— This  complex  derivative  of  quinoline  occurs  as  colorless,  odorless  crystals,  with 
bitter  pungent  taste  :  freely  soluble  in  hot  water.  Originally  brought  forward  by  F. 
Penzolt  as  a  true  stomachic  it  has  been  variously  reported  upon  by  clinicians.  Ac- 
cording to  the  general  reports,  and  especially  to  the  experiments  of  Hofmann,  it 
is  practically  nontoxic,  two  grains  per  pound  weight  not  being  sufficient  to  kill  a 
rabbit,  although  after  enormous  doses  free  haemoglobin  appears  in  the  blood. 
Orexin  hydrochlorate  has,  however,  been  entirely  superseded  by  the  orexin  tannate, 
a  yellowish,  tasteless,  odorless  powder,  insoluble  in  water  but  freely  soluble  in  acid 
solutions,  and  consequently  in  the  gastric  juice.  There  seems  to  be  little  doubt  but 

*  See  Husemann  (Die  Pflanzenstoffe). 


STOMACHICS.  625 

that  orexin  tannate  is  a  valuable  gastric  stimulant  in  all  those  cases  in  which  a  simple 
bitter  is  indicated,  and  that  it  is  contra-indicated  by  gastric  inflammation  or  hyper- 
acidity, and  by  gastric  ulcer.  It  is  stated,  also,  to  be  effective  against  the  vomiting 
following  the  use  of  opium,  chloroform,  and  other  narcotics,  and  also  in  the  vomiting 
of  pregnancy.  It  is  chemically  incompatible  with  iron  salts.  Dose,  five  to  twelve 
grains,  one  to  two  hours  before  meals.  Owing  to  the  insolubility  of  the  salt  it  is 
much  better  to  give  it  in  powder  than  in  tablets. 

AROMATICS. 

The  aromatic  oils  are  essentially  local  irritants,  causing  when  taken 
into  the  mouth  intense  burning  pain,  and  when  confined  upon  the  skin, 
rubefaction,  blistering,  and  finally,  if  the  contact  be  very  prolonged, 
more  destructive  changes.  Internally,  taken  in  very  large  doses,  they 
cause  burning  pain  in  the  stomach,  increased  activity  of  the  circulation, 
and  a  species  of  intoxication.  In  sufficiently  large  quantities  they  are 
irritant  narcotic  poisons.  When  administered  in  therapeutic  doses  they 
act  almost  exclusively  upon  the  alimentary  canal.  As  compared  with 
that  of  the  simple  bitters,  their  influence  is  more  powerful  and  more  tran- 
sient. They  do  not  permanently  increase  the  digestive  power,  but  sim- 
ply increase  action  for  the  time  being.  They  are  employed  chiefly  to 
increase  the  immediate  stimulant  effect  of  bitter  tonics  upon  the  secretory 
digestive  glands  ;  as  carminatives,  to  stimulate  the  intestines  to  contract 
upon  and  expel  flatus  ;  to  prevent  the  griping  of  purgatives  ;  to  disguise 
the  taste  of  medicines,  and  to  render  nauseating  drugs  acceptable  to  the 
stomach  ;  and  to  act  as  condiments  and  aid  in  the  digestion  of  the  food. 

It  is  probable  that  aromatics  directly  after  their  ingestion  affect  more  powerfully 
the  digestive  glandular  apparatus  than  do  bitter  tonics,  since  Gottlieb 7  has  shown 
that  such  substances  as  mustard,  which  are  local  irritants  to  the  stomach,  cause  a 
very  marked  increase  in  the  secretion  of  the  pancreatic  fluids.  Even  when  the 
gland  had  almost  ceased  its  function,  oil  of  mustard  introduced  into  the  stomach 
or  duodenum  caused  active  secretion  in  the  pancreas.  Quassia,  taken  as  a  type  of 
the  bitters,  had  no  effect  on  the  pancreatic  activity. 

Injected  into  the  circulation,  most  volatile  oils  lower  the  blood-press- 
ure by  depressing  the  heart's  action,  and  even  in  comparatively  small 
doses  may  cause  immediate  diastolic  arrest.  In  this  respect  oil  of  cloves 
is  one  of  the  most  powerful.  Their  cardiac  action  is  undoubtedly  direct 
and  upon  the  heart  itself :  other  muscular  structures  would  seem  to  be 
similarly  affected,  as  H.  Kobert 8  has  found  that  the  oil  of  mace  directly 
lowers  muscular  excitability. 

When  in  concentrated  form  almost  all  of  the  volatile  oils  are  direct 
paralyzants  to  nerve-tissues,  and  seem  to  act  especially  upon  the  sensory 
and  peripheral  nerve-endings  ;  hence  most  of  them  are  local  anaesthetics, 
and  some  are  used  for  this  purpose  in  practical  medicine.  Most  of  them 
also  possess  antiseptic  properties. 

Some  of  the  tonic  drugs  containing  a  volatile  oil  also  have  in  them 
a  bitter  principle  which  modifies  their  action.  Such  drugs  may  be  known 

40 


626  LOCAL    REMEDIES. 

as  aromatic  bitters ;  as  bitters  they  are  less  powerful  than  such  drugs  as 
quassia,  and  are  especially  indicated  when  the  stomach  is  delicate  and 
easily  nauseated. 

Inflammation  of  the  stomach  or  bowels  is  the  chief  centra-indication 
to  the  use  of  aromatics.  Unlike  the  simple  bitters,  they  are  often  very 
useful  in  diarrhcea  of  nervous  irritability  or  of  relaxation,  when  no  decided 
inflammation  exists. 

CINNAMOMUM. — The  U.  S.  Pharmacopoeia  recognizes  the  barks  of 
undetermined  species  of  the  genus  Cinnamon  and  the  CINNAMOMUM 
SAIGONICUM,  or  Saigon  Cinnamon,  which  comes  from  Cochin  China  ;  it 
also  recognizes  Ceylon  Cinnamon,  the  bark  of  the  Cinnamomum  zeylani- 
cum.  Much  of  the  cinnamon  of  the  markets  comes  from  China  and  is 
known  as  Cassia  Bark,  or  Chinese  Cinnamon.  Of  these  barks  the  Ceylon 
is  considered  the  finest  and  the  Cassia  the  poorest  in  quality.  They  all 
contain  tannic  acid  and  a  yellowish  volatile  oil  (OLEUM  CINNAMOMI,  U.  S. ) 
which,  on  account  of  its  great  fragrance  and  very  pleasant  taste,  is  largely 
used,  in  doses  of  from  one  to  three  drops  (0.06-0. 1 8  C.c. ),  as  an  adjuvant 
or  to  disguise  the  flavor  of  less  agreeable  drugs.  Oil  of  cinnamon  contains 
seventy-five  to  ninety  per  cent,  of  Cinnamic  Aldehyde — Cinnaldehydum, 
U.  S. ,  which  may  also  be  prepared  synthetically.  It  is  a  colorless,  aromatic 
liquid,  having  the  same  medical  properties  as  has  the  oil  itself.  Cinnamon 
water  (AQUA  CINNAMOMI — oil  0.2  per  cent.,  U.  S. )  is  used  solely  as  a 
vehicle.  The  spirit  of  cinnamon  (SPIRITUS  CINNAMOMI — oil  ten  per 
cent.,  U.  S. )  is  administered  in  doses  of  one-half  to  one  fluidrachm 
(2-4  C.c.);  the  tincture  (TiNCTURA  CINNAMOMI — Saigon  Cinnamon — 
twenty  per  cent.,  U.  S. )  in  doses  of  one  to  two  fluidrachms  (4-7  C.c.). 
PULVIS  AROMATICUS.  U.  S. — Aromatic  Powder  (cinnamon,  ginger, 
cardamom,  nutmegs)  is  an  elegant  carminative  in  doses  of  from  ten  to 
twenty  grains  (0.6-1.3  Gm. ). 

FLUIDEXTRACTUM  AROMATICUM.  U.  S. — Aromatic  Fluid  Extract  is 
a  concentrated  tincture  of  aromatic  powder,  15  minims  (i  C.  c. )  of  which 
represent  15  grains  (i  Gm.)  of  the  powder. 

CARYOPHYLLUS.  U.  S. — Cloves  are  the  unexpanded  flowers  of  Eu- 
genia aromatica,  a  tree  growing  in  the  Molucca  Islands.  OLEUM  CARYO- 
PHYLLI,  U.  S. ,  is  an  exceedingly  pungent,  yellowish,  volatile  oil,  be- 
coming dark  by  age,  which,  besides  being  used  as  a  carminative  and  an 
aromatic,  is  often  employed  to  benumb  sensitive  dentine,  or  even  exposed 
pulp,  in  caries  of  the  teeth.  Dropped  on  a  piece  of  cotton  and  placed 
in  the  cavity,  it  will  frequently  cure  toothache. 

Oil  of  cloves  is  chiefly  composed  of  an  unsaturated  phenol,  EUGENOL, 
U.  S. ,  which  is  a  colorless  or  yellowish  thin  liquid,  having  the  odor  and 
taste  of  cloves,  and  becoming  on  exposure  to  the  air  dark  and  thick.  It 
may  be  used  for  the  same  purposes  as  is  the  oil  of  cloves.  Dose  of  oil 


STOMACHICS.  627 

of  cloves  or  of  eugenol,  one  to  four  minims  (0.06-0.24  C.c. ).  Clove  tea, 
two  drachms  to  the  pint,  an  infusion  made  with  boiling  water,  is  often  used 
domestically  in  doses  of  a  wineglassful  or  more  for  acute  menstriial  sup- 
pression and  as  a  sudorific. 

MYRISTICA.  U.  S. — Nutmeg  is  the  kernel  of  the  fruit  of  Myristica 
fragrans,  a  tree  growing  in  the  Molucca  Islands.  The  nutmeg  contains 
both  a  fixed  and  a  volatile  oil.  Mace  (U.  S.  P.  1890)  is  the  arillus  or 
outer  imperfect  supernumerary  coating  of  the  seed.  :Both  mace  and 
nutmeg  depend  for  their  activity  upon  the  volatile  oil  (OLEUM  MYRIS- 
TIC^E,  U.  S. )  which,  when  injected  intravenously  into  the  lower  animals, 
causes  loss  of  coordination,  tremors,  profound  coma,  abolition  of  all  re- 
flexes, and  finally  death  from  respiratory  paralysis,  its  influence  upon  the 
circulation  being  comparatively  feeble.*  In  man,  one  or  two  nutmegs 
will  usually  suffice  to  produce  a  dreamy,  half-unconscious  intoxication, 
and  severe  or  even  fatal  poisoning  has  been  caused  by  larger  quantities. 
The  symptoms  of  poisoning  have  been  dizziness,  stupor  deepening  into 
coma,  muscular  relaxation,  dilated  pupils,  slow  pulse  and  respiration,  and 
suppression  of  urine,  ending  in  death  from  respiratory  paralysis,  f  Dose, 
of  oil,  ten  to  twenty  drops  (0.6—1.2  C.c.).  In  animals  fatally  poisoned 
fatty  degeneration  has  been  found  (Wallace. ) 

PIMENTA.  U.  S. — Pimenta,  or  Allspice,  is  the  unripe  berries  of  Pi- 
menta  officinalis,  a  tree,  native  in  the  West  Indies.  Dose  of  the  volatile 
oil  (OLEUM  PIMENT^E,  U.  S. ),  two  to  five  drops  (0.12-0.3  C.c.). 

CARDAMOMUM.  U.  S.  —  Cardamoms  are  the  fruit  of  Elettaria  repens, 
which  grows  in  the  East  Indies.  They  consist  of  tough,  seemingly 
fibrous,  generally  more  or  less  triangular  dry  and  tasteless  capsules,  con- 
taining a  number  of  small,  hard,  very  aromatic  seeds.  The  colorless, 
highly  aromatic,  volatile  oil  is  not  official.  Cardamom  is  a  very  grateful 
aromatic,  much  less  stimulating  and  heating  than  most  of  the  other  drugs  of 
its  class.  The  dose  of  the  tincture  (TINCTURA  CARDAMOMI — twenty  per 
cent.,  U.  S.)  is  one  fluidrachm  (4  C.c.).  The  compound  tincture  (TiNC- 
TURA  CARDAMOMI  COMPOSITA — two  per  cent.,  U.  S.)  is  a  very  elegant 
addition  to,  or  vehicle  for,  tonic  medicines  ;  dose,  one  to  two  fluidrachms 
(4-7  C.c.) 

ZINGIBER.  U.  S. — Ginger  is  the  dried  rhizome  or  root-stock  of  Zin- 
giber  officinale,  growing  in  the  East  and  West  Indjes.  Green  Ginger 
is  the  fresh  rhizome.  Black  Ginger  is  the  root-stock  dried  with  the 

*  Experiments  of  H.  C.  Wood  ;  also  Cadeac  and  Meunier  (Journ.  Med.  Vet.,  Lyons, 
1890). 

t  Fatal  case,  N.  Y.  Med.  Record,  Nov.  1886.   Collection  of  Cases,  George  B.  Wallace, 

C.  M.  R.  V.,  362. 


628  LOCAL   REMEDIES. 

epidermis  on  ;  White  or  Jamaica  Ginger  is  the  same,  deprived  of  its 
epidermis.  The  fresher  ginger  is  the  greater  is  its  power,  and  by  time 
and  exposure  it  becomes  completely  inert.  Its  active  principles  are  a 
soft,  acrid,  aromatic  resin,  and  a  yellow,  volatile  oil.  Ginger  is  much 
used  in  domestic  medicine  as  a  stimulant  carminative  in  colic;  given  in 
hot  water,  it  is  also  used  as  a  sudorific  and  stimulant  in  the  pain  due  to 
suddenly  suppressed  menstruation.  It  is  often  added  with  advantage  to 
other  remedies  in  dyspepsia.  The  syrup  (SYRUPUS  ZINGIBERIS — three 
per  cent. ,  U.  S. )  is  used  only  as  a  cordial  drink  or  vehicle,  in  doses  of 
from  half  a  fluidounce  to  a  fluidounce  (15-30  C.c. ).  The  tincture,  often 
called  Essence  of  Ginger  (TINCTURA  ZINGIBERIS — twenty  per  cent., 
U.  S. ) ,  is  the  most  commonly  employed  preparation  ;  the  dose  is  half  a 
teaspoonful  to  a  teaspoonful  (2-4  C.c.).  The  dose  of  the  fluid  extract 
(FLUIDEXTRACTUM  ZINGIBERIS,  U.  S.)  is  five  to  ten  drops  (0.3-0.6  C.c.). 
The  oleoresin  (OLEORESINA  ZINGIBERIS,  U.  S.)  is  used  as  a  stimulant 
addition  to  tonic  pills  ;  the  dose  is  from  half  a  minim  to  two  minims 
(0.03-0.12  C.c. ). 

PIPER.  U.  S. — Black  Pepper  is  the  unripe  fruit  of  Piper  nigrum,  a 
woody  vine-like  plant  growing  in  the  East  Indies.  White  Pepper  is  the 
ripe  berries  stripped  of  their  skin  and  dried.  It  is  much  less  pungent 
than  the  black  pepper.  The  active  principles  of  black  pepper  are  a 
soft,  acrid  resin,  a  pungent,  fiery,  volatile  oil,  and  piperin. 

In  1819  Oersted  discovered  Piperin  (PIPERINUM,  U.  S.),  which  crys- 
tallizes in  colorless,  glistening,  four-sided,  truncated  prisms,  of  a  neutral 
reaction,  but  capable  of  combining  with  acids  to  form  salts.  When  pure 
it  is  tasteless  ;  but  very  commonly  it  has  a  burning  taste,  due  to  the 
presence  of  some  of  the  volatile  oil  of  pepper.  The  possession  of  very 
active  antiperiodic  properties  has  been  asserted  for  piperin,  and  it  was 
for  a  time  employed  in  intermittent  fever  ;  but  it  has  fallen  into  complete 
disuse.  The  dose  as  an  antiperiodic  is  four  grains  (0.26  Gm.),  repeated 
once  or  twice  during  the  interval  between  the  paroxysms.  Pepper  is 
very  largely  used  as  a  condiment ;  but,  as  its  taste  is  more  hot  than 
aromatic,  it  is  rarely  given  internally  in  medicine  except  as  an  addition 
to  simple  bitters  or  to  antiperiodics,  generally  in  the  form  of  the  oleoresin 
(OLEORESINA  PIPERIS,  U.S.),  the  dose  of  which  is  one-half  to  one 
grain  (0.03-0.06  Gm. ).  In  atonic  dyspepsia  the  latter  preparation  is  an 
excellent  adjuvant  to  tonic  pills.  Schiffer  is  said  (Fliess)  to  have  used 
piperin  successfully  in  a  case  of  vaginismus,  by  injecting  three-tenths  of 
a  grain  (0.018  Gm. )  hypodermically  near  the  vaginal  entrance.  In 
using  piperin  by  hypodermic  injections  it  is  of  the  utmost  importance 
to  see  that  it  is  free  from  the  oil  of  pepper. 

CAPSICUM.  U.  S. — The  U.  S.  Pharmacopoeia  now  recognizes  only  the 
small, — less  than  an  inch  long, — very  fiery  fruit  of  Capsicum  fastigiatum, 
the  African  Pepper,  or  Chillies.  The  large,  bright  red,  conical  or  ovate, 


STOMACHICS.  629 

comparatively  mild  peppers  of  the  market  are  from  C.  annuum  ;  they  are 
sometimes  known  as  West  India  peppers.  Capsicum  contains  as  its 
active  principle  an  exceedingly  acrid  oleoresin.* 

Capsicum  is  a  very  powerful  local  irritant,  its  oleoresin  when  applied 
to  the  skin  producing  in  a  very  few  minutes  intense  pain  and  redness, 
and  finally  destroying  the  cuticle.  In  the  alimentary  canal  it  acts  in  a 
similar  manner  :  thus,  moderate  doses  produce  merely  a  pleasant  feeling 
of  warmth  in  the  stomach,  while  overdoses  may  cause  gastro-intestinal 
inflammation,  with  severe  pain,  as  well  as  vomiting  and  purging,  followed 
after  a  time  by  strangury  and  other  evidences  of  genito-urinary  irritation. 
The  chief  use  of  Cayenne  Pepper  is  as  a  condiment ;  yet  it  is  often  added 
with  advantage  to  tonic  pills  to  increase  their  immediate  action  on  the 
stomach.  When  there  is  habitual  feeble  digestion,  with  flatulence,  its 
free  use  on  food  may  do  good.  In  adynamic  diseases,  especially  as  occur- 
ring among  drunkards,  capsicum  is  often  very  useful  by  stimulating  the 
stomach  up  to  the  point  of  digesting  food.  Locally,  either  as  the  diluted 
tincture  in  a  gargle  or  applied  in  powder  or  tincture  by  means  of  a  swab, 
it  is  useful  in  severe  tonsillitis,  especially  in  that  accompanying  scarlet 
fever.  The  dose  of  capsicum  is  four  to  five  grains  (o.  26-0. 3  Gm. )  in  pill ; 
of  the  very  efficient  oleoresin  (OLEORESINA  CAPSICI,  U.  S. ),  from  one- 
quarter  to  one-half  a  minim  (0.016—0.032  C.c. )  ;  of  the  tincture  (TiNC- 
TURA  CAPSICI — ten  per  cent.,  U.  S. ),  one-half  to  one  fluidrachm  (2-4 
C.c. )  doses  to  drunkards;  of  the  fluid  extract  (FLUIDEXTRACTUM  CAPSICI, 
U.  S. ),  one-half  to  one  minim  (0.03-0.06  C.c.). 

OLEUM  CAJUPUTI.  U.  S. — The  Oil  of  Cajuput  is  obtained  from  the 
leaves  of  Melaleuca  leucadendron,  a  tree  growing  in  the  Molucca  Islands. 
This  volatile  oil  is  of  a  green  color,  a  peculiar  fragrant  odor,  and  a  burn- 
ing, camphoraceous  taste.  It  is  not  very  irritating  to  the  skin,  but  is 
exceedingly  destructive  to  low  forms  of  life,  and  consequently  has  been 
used  as  a  parasiticide  externally,  and  even  internally  against  the  Ascar- 
jdes.  In  intestinal  pain  and  spasm  and  in  serous  diarrhoea  it  is  efficient, 
especially  in  combination  with  chloroform,  camphor,  and  opium.  As  a 
counter-irritant,  it  has  been  used  in  rheumatism ;  as  a  stimulant  to  the 
skin,  in  psoriasis,  acne  rosacea,  and  pityriasis.  Dose,  from  ten  to  fifteen 
drops  (0.6-1  C.c. ). 

OLEUM  SASSAFRAS.  U.  S. — The  Oil  of  Sassafras  is  largely  used  in 
the  arts  on  account  of  its  cheapness  and  pleasant  flavor.  It  is  capable  of 
producing  very  marked  narcotic-poisoning,9  and  is  said  to  act  upon  the 
lower  animals  as  a  convulsant  and  narcotic.  John  Bartlett 10  asserts  that 
it  is  capable  of  inducing  uterine  contractions,  and  reports  cases  of  abor- 
tion caused  by  it. 

AURANTII  AMARI  CORTEX — Bitter  Orange  Peel.  U.  S. — The  fluid 
extract  (FLUIDEXTRACTUM  AURANTII  AMARI,  U.  S.)  and  the  tinc- 

*  The  name  of  Capsicin  has  been  applied  by  different  observers  to  the  oil,  to  the  resin, 
and  to  their  combination,  but  has  no  definite  meaning. 


63o  LOCAL   REMEDIES. 

ture  (TINCTURA  AURANTII  AMARI — twenty  per  cent.,  U.  S. )  may  be 
given  respectively  in  doses  of  twenty  minims  (1.2  C.c. )  and  a  fluidrachm 
(4  C.c. ).  AURANTII  DULCIS  CORTEX — Sweet  Orange  Peel.  U.  S.— 
Of  the  syrup  (SYRUPUS  AURANTII — five  per  cent.,  U.  S. )  the  dose  is  a 
dessertspoonful  (7  C.c.),  of  the  tincture  (TINCTURA  AURANTII  DULCIS— 
fifty  per  cent.,  U.  S. ),  a  tablespoonful  (15  C.c.).  The  orange  peels 
are  themselves  scarcely  medicinal,  but  are  official  as  affording  prepara- 
tions much  used  as  vehicles.  LIMONIS  CORTEX,  U.  S. ,  or  Lemon  Peel 
(SPIRITUS  LIMONIS — five  per  cent.,  U.  S. ),  is  also  used  for  flavoring 
purposes. 

AURANTII  FLORES. — The  flowers  of  the  orange  are  official  for  the 
preparation  of  Orange  Flower  Water  (AQUA  AURANTII  FLORUM,  U.  S. ), 
which  is  used  as  an  elegant  vehicle,  free  from  medicinal  properties. 

The  fruits  of  the  following  umbelliferous  plants — Foeniculum  capil- 
laceum,  Carum  carui,  Coriandrum  sativum,  and  Pimpinella  anisum — are 
official  under  the  respective  names  of  FCENICULUM  (fennel),  CARUM 
(Caraway),  CORIANDRUM  {Coriander),  and  ANISUM  (Anise).  They  all 
depend  for  their  virtues  upon  volatile  oils  which  are  official.  The  oil  of 
anise  of  commerce  is  largely  the  product  of  a  Chinese  tree,  the  Illicium 
anisatum,  or  Star  Anise,  from  whose  five-  to  ten-rayed  capsular  fruit  it  is 
obtained  by  distillation.  The  AQUA  FCENICULI  (o.  2  per  cent. )  and  the 
SPIRITUS  ANISI  (ten  per  cent.)  are  official.  All  of  these  fruits  and 
their  preparations  may  be  used  as  carminatives  and  stomachics. 

The  herbal  portions  of  the  following  mints  are  official  :  Salvia  offi- 
cinalis,  Mentha  piperita,  Mentha  viridis,  and  Melissa  officinalis.  They  are 
respectively  known  as  Sage  (SALVIA),  Peppermint  (MENTHA  PIPERITA), 
Spearmint  (MENTHA  VIRIDIS),  and  Balm  (MELISSA).  The  important 
U.  S.  preparations  of  them  are  as  follows  :  AQUA  MENTH^E  PIPERITJE 
{Peppermint  Wafer)  and  AQUA  MENTHA  VIRIDIS  (Spearmint  Water), 
both  very  frequently  used  as  vehicles.  SPIRITUS  MENTHA  VIRIDIS  and 
SPIRITUS  MENTH^E  PIPERIT^E  {Essence  of  Spearmint  and  Essence  of 
Peppermint),  used  as  carminatives,  in  doses  of  from  ten  to  twenty  drops 
(0.6-1.2  C.c. ).  The  oils  of  lavender,*  peppermint,  and  spearmint  are 

*  Masoin  and  Bruylant  have  studied  to  some  extent  the  physiological  action  of 
the  oils  of  lavender,  rosemary,  marjoram,  and  aspic  (Lavandula  spica  L.)  (Bull.  Acad. 
Roy.  Med.  de  Bruxelles,  1879,  558;  see  also  Schmidt's  Jahrb.,  clxxx.  123,  and  Cadeac 
and  Meunier,  Compt.-Rend.  Soc.  Biolog.,  1889,  and  Lyon  Med.,  1889).  In  frogs  they 
caused  generally  paralysis,  with  loss  of  reflex  activity,  the  muscles  being  intact,  and  the 
sensory  nervous  apparatus  being  affected  before  the  motor.  Upon  the  higher  animals  a 
similar  effect  was  produced,  except  that  oil  of  rosemary  caused  epileptiform  convulsions. 
Oil  of  Peppermint  ( M.  piperita)  has  been  studied  by  S.  D.  Markuson  (Inaug.  Dis., 
Halle,  1877;  Schmidt's  Jahrb.,  clxxx.  122),  who  finds  that  while  very  small  doses  in- 
crease, larger  ones  decrease  the  blood-pressure  and  lower  the  bodily  temperature.  Most 
of  the  volatile  oils  have  germicidal  properties,  and  the  oil  of  peppermint  has  been  highly 
praised  as  a  practical  dressing  for  burns,  wounds,  etc.  (See  The  Medical  Reporter  of 
India,  vi.) 


STOMACHICS.  631 

also  official,  and  may  be  used  in  doses  of  from  three  to  ten  drops  as  car- 
minatives. The  oil  of  peppermint  has  been  long  used  in  China  as  a 
local  application  in  neuralgia  and  subacute  rheumatism,  and  is  sometimes 
very  effective  in  relieving  pain.  It  should  be  applied  to  the  part  until 
the  burning  is  no  longer  endurable,  when  it  may  be  removed  and  petro- 
latum applied.  (See  also  MENTHOL.)  SPIRITUS  LAVANDUL^E  {Spirit 
of  Lavender),  a  very  elegant  and  agreeable  stomachic  and  cordial,  is 
made  by  dissolving  oil  of  lavender  flowers  in  alcohol.  Dose,  a  fluidrachm 
to  half  a  fluidounce  (4-30  C.c. ).  Sage  contains  tannin. 

Water  of  Rosemary  has  long  been  believed  to  have  especial  influence 
upon  the  skin,  and  in  cases  of  acne  a  lotion  composed  of  a  pint  of  this 
water  and  an  ounce  of  the  flowers  of  sulphur  has  been  often  effective. 


AROMATIC   BITTERS. 

ANTHEMIS.  U.  S. — CHAMOMILE. — Roman  or  true  Chamomile,  the 
dried  flowers  of  Anthemis  nobilis,  a  composite  of  Europe,  contains  a  bluish 
or  sometimes  greenish  volatile  oil,  a  bitter  principle,  and  a  small  amount 
of  tannin.  The  infusion  (one  ounce  to  a  pint)  is  a  mild  stomachic  in 
doses  of  one  to  two  wineglassfuls.  MATRICARIA,  U.  S. ,  or  German 
Chamomile,  the  flowers  of  Matricaria  Chamomilla,  is  much  less  agreeable 
and  effective. 

SERPENTARIA.  U.  S. —  Virginia  snakeroot,  the  root  of  Aristolochia 
Serpentaria  and  of  A.  reticulata,  small  herbal  plants  of  the  United  States, 
contains  a  volatile  oil,  a  yellowish-green  resin,  and  a  bitter  principle.  It 
is  an  elegant  stimulant  tonic,  especially  useful  as  an  adjuvant  to  more 
powerful  bitters.  The  dose  of  the  tincture  (TINCTURA  SERPENTARIA — 
twenty  per  cent.,  U.  S. )  is  one  to  two  fluidrachms  (4-7  C.c.);  of  the 
fluid  extract  (FLUIDEXTRACTUM  SERPENTARIA,  U.  S.),  twenty  drops 
(1.2  Gc). 


REFERENCES. 
STOMACHICS.  7.  GOTTLIEB  ....  A.   E.  P.  P.,  1894,  xxxiii. 


•,  -  -  8.    KOBBKT    .....  AE.  P.  P,  XV.  ». 

I  £  V,89*5; 

B'G  T    c'uiT-o  10.  BARTLBTT  ....  Chi.  M.  J..  Dec.  :885. 

J  ROUX  .......  C.'  R.'  S.  B.,  1884,  i.  33-  «•  BORISSOW    ....  A.  E.  P.  P..  1904.  H.  3f>3- 

•6.  LIEBIG  and  WOHLER  .  Ann.  Chem.  Pharm.. 
xxii.  i. 


FAMILY   II.— EMETICS. 


EMETICS  are  those  drugs  which  are  employed  in  the  practice  of  medi- 
cine for  the  purpose  of  producing  emesis,  or  vomiting. 

Vomiting  occurs  under  two  provocations,  or  in  two  manners.  Thus, 
a  mental  impression,  or  a  disordered  state  of  the  blood,  may  influence 
the  nerve-centres  directly,  and  emesis,  spoken  of  as  centric,  results  ;  or  a 
peripheral  irritation  in  the  stomach  itself,  or  in  some  other  organ,  as  in 
the  kidneys,  may  induce  vomiting  precisely  similar  in  the  method  of  its 
production  to  the  more  ordinary  reflex  movements  ;  such  vomiting  is 
called  reflex  or  excentric. 

Emetics  produce  their  results  in  both  of  these  methods.  Thus, 
tartar  emetic  has  been  believed  to  affect  the  centres  directly,  so  as  to 
cause  centric  vomiting,  while  copper  sulphate  has  been  believed  to  irri- 
tate the  mucous  membranes  of  the  stomach,  so  as  to  produce  reflex 
vomiting.  Much  doubt,  however,  has  .been  thrown  upon  the  old  views, 
and  it  is  probable  that  most  emetics  have  a  double  influence.  Thus, 
the  purging  of  veratria  or  of  tartar  emetic  is  almost  certainly  connected 
with  its  elimination,  and  is  probably  due  to  a  direct  action  of  the  circu- 
lating poison  upon  the  intestinal  mucous  epithelium,  gland-cells,  and 
peripheral  nerves.  It  seems  a  priori  almost  a  necessity  that  the  vomit- 
ing caused  by  these  poisons  is  produced  in  the  same  way  as  is  the  purging. 
D'Ornellas  has  found  that  when  emetine  is  injected  into  the  veins  of 
animals  the  vomiting  occurs  simultaneously  with  the  elimination  of  the 
alkaloid  from  the  gastric  mucous  membrane,  and  asserts  that  Klei- 
mann  and  Simonowitsch  have  determined  the  same  thing  with  antimony. 
Further,  antimony  seems  to  cause  vomiting  partly  by  acting  upon  the 
centres,  partly  by  irritating  the  peripheral  nerve.  Irritant  emetics  are 
more  prompt  than  those  which  chiefly  affect  the  nerve-centres  ;  they 
always  cause  less  nausea  and  general  systemic  disturbance  than  do  the 
centric  emetics. 

Another  evident  practical  fact  is,  that  while  centric  emetics  will  act 
in  whatever  way  they  are  introduced  into  the  system,  the  mechanical 
emetics  must  be  exhibited  by  the  stomach.  Thus,  apomorphine  may  be 
given  by  hypodermic  injection,  but  mustard  must  be  taken  by  the  mouth. 
Nevertheless,  it  is  probable  that  most  of  the  so-called  ' '  irritant  emetics' ' 
act  in  part  by  being  absorbed,  since  A  Sacher l  has  found  that  even  zinc 
sulphate  will,  when  injected  in  proper  dose  into  the  blood,  produce 
632 


EMETICS.  633 

vomiting,  and  Brunton  and  West  have  demonstrated  that  a  peptone  of 
copper  injected  into  a  vein  causes  violent  vomiting. 

A  very  curious  property  of  emetics  has  been  pointed  out  by  E.  Harnack,*  who, 
as  the  result  of  an  elaborate  investigation,  affirms  as  a  law  that  all  specific  emetic 
substances  destroy,  even  when  in  relatively  small  dose,  the  excitability  of  striated 
muscular  fibre.  Harnack  seems  to  establish  the  general  truth  of  this ;  but  that 
it  is  a  universal  law  is  scarcely  probable,  and  the  connection  between  the  two 
properties  is  very  obscure.  According  to  H.  Kobert,*  antimony  has  an  effect  on 
muscle-fibre  only  when  the  contact  is  prolonged. 

In  regard  to  the  phenomena  of  vomiting,  there  are  a  few  points  to 
which  it  is  necessary  here  to  call  attention.  First  of  these  is  the  fact 
that  nausea  always  produces,  or  is  accompanied  by,  muscular  relaxation. 
Vomiting  may  take  place,  as  from  mustard,  without  much  relaxation  ; 
but  when  it  is  accompanied  by  much  nausea  the  whole  system  is,  as  it 
were,  unbent,  the  skin  relaxed  and  bedewed  with  perspiration,  the  pulse 
soft  and  feeble,  the  muscular  system  limp  and  incapable  of  exertion,  and 
the  mental  acts  almost  suspended.  During  violent  vomiting  the  blood  is 
driven  to  the  head,  so  that  the  whole  exterior  of  the  cranium,  and  prob- 
ably the  interior  also,  becomes  very  much  congested.  The  abdominal 
circulation  is  greatly  affected,  and  the  blood  is,  as  it  were,  squeezed 
out  of  the  portal  vein  and  its  tributaries.  The  matters  rejected  consist 
of  the  contents  of  the  stomach,  and,  in  repeated  vomiting,  also  those 
of  the  duodenum.  The  secretion  from  the  gastric  mucous  membrane 
is  very  much  enhanced,  and  without  doubt  is  more  or  less  modified. 
Bile  in  ejecta  is  to  be  recognized  by  the  green  color  and  the  bitter  taste, 
or  more  infallibly  by  testing  with  the  proper  reagents. 

The  indications  for  the  use  of  emetics  are  as  follows  : 

1.  To  unload  the  Stomach. — For  this  purpose  they  are  employed  in 
poisoning,  or  when  the  stomach  is  oppressed  by  indigestible  substances 
or  by  its  own  acrid,  perverted  secretions.     The  symptoms  induced  by 
irritating  materials  in  the  stomach  are  various,  and  sometimes  it  requires 
a  good  deal  of  tact  or  experience  to  recognize  their  cause.     Among 
them  may  be  mentioned  a  feeling  of   weight  or  load  in  the  stomach, 
gastric  distress,  or  severe  cramp  or  spasmodic  pains,  with  or  without 
some  nausea  and  retching.      In  other  cases  no  local  manifestations  of 
trouble  may  be  present.     Thus,    convulsions  in  children  are  very  fre- 
quently the  result  of  gastric  irritation,  and  are  at  once  relieved  by  empty- 
ing the  stomach.      In  adults,  apoplectiform  coma  may  offer  a  similar  his- 
tory.    Occasionally  urticaria,  or  hives,  and  not  rarely  severe  headache, 
have  a  similar  origin,  and  require  a  similar  treatment. 

2.  To  affect  the  Abdominal  Viscera  and  Circulation. — In  congestions 
of  the  portal  circulation,  especially  such  as  follow  a  debauch,  and  in  the 
condition  of  digestive  derangement  known  as  biliousness,   emetics  are 
often  of  service.     In  catarrhal  jaundice  they  may  effect  much  good  by 
causing  dislodgement  of   the  mucus  plugging  the  ducts.     They  have 


634  LOCAL    REMEDIES. 

been  employed  in  cases  of  biliary  calculi ;  but  the  chances  of  forcing 
out  the  calculus  by  external  violence  are  probably  no  greater  than  those 
of  lethal  rupture  of  the  gall-bladder. 

3.  To  dislodge  Substances  from  the  Respiratory  Passages. — For  this 
purpose   emetics  are  sometimes  used  when  foreign  bodies  have  found 
entrance  into  the  larynx  ;  but  it  is  chiefly  in  membranous  croup  that  the 
present  indication  is  met  with.     The  emetics  chosen  for  this  purpose 
should  be  such  as  act  with  violence  without  producing  much  nausea  or 
systemic  disturbance  :  the  mechanical  emetics  are  therefore  the  best. 

4.  To  produce  Muscular  Relaxation. — The  introduction  of  anaesthesia 
has  rendered  the  use  of  emetics  to  meet  this  application  almost  obsolete. 
Occasionally,  however,  in  asthmatic  or  other  spasmodic  affections  of  the 
respiratory  organs,  emetics  are  still  employed.      For  this  purpose  the 
drugs  causing  much  nausea  are  preferred.      In  adults,  lobelia  is  the  best ; 
in  children,  ipecacuanha.      Nauseating  rather  than  emetic  doses  should 
be  employed. 

Contra-indications. — The  chief  contra-indications  to  the  use  of  emetics 
are  the  existence  of  congestion  of  the  brain  and  of  gastric  inflammation. 
Advanced  pregnancy,  and  hernia,  while  they  do  not  positively  centra- 
indicate  the  use  of  emetics,  should  cause  great  caution  to  be  practised 
in  their  employment. 

ADMINISTRATION. — Emetics  should,  as  a  general  rule,  be  given  in  a 
full  dose,  so  as  to  avoid  unnecessary  repetition,  and  should  be  adminis- 
.tered  dissolved  in  water  or  in  syrup.  Their  action  should  be  assisted 
by  frequent  and  copious  draughts  of  tepid  water,  which  also  have  the 
advantage  of  rendering  the  vomiting  less  painful.  When  for  any  reason 
protracted  nausea  is  desired,  the  doses  should  be  small  and  repeated  at 
short  intervals. 

Hyperemesis  may  advantageously  be  divided  into  two  varieties  :  first, 
such  as  is  due  to  overdoses  of  depressing  centric  emetics  ;  second,  such 
as  arises  from  irritation  of  the  stomach,  as  by  mechanical  emetics.  The 
treatment  of  the  first  of  these  consists  in  the  enforcement  of  absolute 
quiet  in  the  horizontal  position,  the  free  use  of  opium  enemata,  the 
application  of  counter-irritants  to  the  epigastrium,  and  the  use  of  alco- 
holic stimulants.  The  latter  should  be  given  in  hot  water,  and  should 
not  be  too  much  diluted.  We  have  seen  raw  brandy  arrest  at  once  the 
most  alarming  centric  emesis  after  the  failure  of  other  methods.  Cocaine, 
creosote,  chloroform,  or  chloroform  and  volatile  oils  are  sometimes  of  value 
in  this  form  of  hyperemesis.  When  excessive  vomiting  is  due  to  some 
irritant  substance,  the  stomach  should  be  thoroughly  washed  out  by 
large  draughts  of  warm  mucilage,  opium  given  by  the  rectum,  a  mustard 
plaster  or  blister,  or,  often  better  still,  leeches  applied  to  the  epigas- 
trium, and  no  medicine  at  all  be  taken  into  the  inflamed  viscus.  The 
swallowing  of  small  pieces  of  ice  is  sometimes  of  service.  If  these 
remedies  fail,  the  treatment  of  this  form  of  hyperemesis  soon  resolves 
itself  into  that  of  gastritis. 


EMETICS.  635 


CENTRIC  EMETICS. 

IPECACUANHA.     U.  S. 

The  U.  S.  Pharmacopoeia  recognizes  the  Cephaelis  Ipecacuanha, 
•growing  in  Brazil,  and  the  C.  acuminata,  growing  in  Colombia,  plants 
whose  roots  respectively  constitute  the  Rio,  Brazilian,  or  Para  ipecac - 
Tianha,  and  the  Carthagena  ipecacuanha.  There  is  at  present  no  sufficient 
reason  for  believing  that  these  plants  are  specially  distinct.  (See  U.  S. 
Dispensatory,  igth  edition.)  The  true  ipecacuanha  plant  has  been  culti- 
vated with  success  in  the  Straits  Settlements,  producing  the  so-called 
Johore  ipecacuanha.  The  South  American  drug  comes  from  wild  plants 
•exclusively. 

The  ipecacuanha  roots  differ  largely  in  the  total  percentage  of  the 
alkaloidal  contents,  hence  the  requirement  of  the  U.  S.  Pharmacopoeia  that 
they  should  contain  at  least  two  per  cent,  of  aggregate  alkaloids.  It  has 
been  believed  by  various  authorities  that  the  Rio  and  Carthagena  ipecac- 
uanhas— because  in  the  former  emetine,  in  the  latter  cephaeline,  predomi- 
nates— are  not  interchangeable;  but  the  reports  of  the  large  drug  firms 
both  in  Europe  and  in  this  country  indicate  that  the  individual  roots  of  either 
vary  as  much  in  the  proportionate  percentage  of  emetine  and  cephaeline 
as  do  Rio  and  Carthagena  ipecacuanha,  and  that,  therefore,  these  two 
ipecacuanhas  may  be  considered  as  therapeutically  identical.  It  is  clear 
that  apothecaries  furnish  to  physicians  the  two  varieties  of  ipecacuanha 
indiscriminately.  Practical  differences  in  their  action  have  not  been  made 
out  by  clinicians  ;  and  the  belief  of  some  experimentalists  that  when  an 
emetic  effect  is  desired  Carthagena  is  best,  and  when  an  expectorant  effect 
is  wished  Rio  ipecac  should  be  used,  is  not  well  founded.*  Ipecacuanha 
occurs  in  pieces  two  or  three  lines  in  thickness,  variously  bent  and  con- 
torted, marked  on  their  surface  with  numerous  prominent  rings,  and  com- 
posed of  an  outer,  thick,  active,  hard,  and  horny  cortex,  and  an  inner, 
light,  inert,  woody  centre.  The  root  has  very  little  odor,  but  the  brown 
powder  has  a  decided  and  peculiar  smell,  and  in  some  persons  excites 
sneezing,  or  even  violent  asthmatic  dyspnoea.  The  taste  is  bitter,  acrid, 
and  nauseous.  The  alkaloid  (emetine)  found  in  1817  by  Pelletier  in 
ipecacuanha  is  now  known  to  be  composed  of  three  alkaloids,  emetine, 
•cephaeline  and  psychotrin.  The  emetine  of  the  older  physiological  inves- 
tigators is  this  alkaloidal  mixture.  In  the  text  of  this  book  it  is  spoken 
of  as  crude  or  commercial  emetine.  Ipecacuanhic  acid,  with  which  the 
alkaloids  are  combined,  according  to  Kimura,27  is  practically  inert, 
although  when  brought  in  contact  with  the  red  blood-corpuscles  outside 
of  the  body  it  dissolves  out  the  haemoglobin. 

*  According  to  the  experiments  of  Carl  Lowin  emetine  is  only  a  feeble  emetic,  whilst 
<:ephaeline  is  a  very  powerful  emetic.  On  the  other  hand,  cephaeline  does  not  act  upon 
the  lungs  at  all,  so  that  the  emetic  influence  of  ipecacuanha  is  dependent  upon  the  pres- 
ence of  cephaeline, — its  expectorant  influence  upon  the  presence  of  emetine. 


636  LOCAL    REMEDIES. 

Local  Action. — Absorption  and  Elimination. — Locally  applied,  ipe- 
cacuanha is  a  decided  irritant,  manifesting  its  action  not  only  upon  mu- 
cous membranes  and  upon  denuded  surfaces,  but  also  causing,  when 
applied  by  inunction,  an  eruption  of  small,  discrete  pustules,  with  a  rather 
large  areola,  followed,  it  may  be,  by  large  pustulation  and  even  severe 
ulceration.  Both  pure  emetine  and  cephaeline  were  found  by  Lowin  to 
be  very  irritant,  and  especially  so  to  mucous  membranes.  Ipecacuanha 
rapidly  yields  its  active  principles  to  absorption.  They  are  probably 
eliminated  by  the  stomach,  intestines  and  kidneys,  but  concerning  this  we 
have  no  definite  knowledge.* 

PHYSIOLOGICAL  ACTION. — When  given  in  small  repeated  doses  to 
man,  ipecacuanha  produces  malaise,  with  nausea,  and  perhaps  an  increase 
of  the  secretions  of  the  salivary  glands  and  of  the  mucous  membranes 
of  the  bronchial  tubes  and  of  the  stomach.  In  large  amounts  it  causes 
vomiting,  accompanied  by  only  a  moderate  amount  of  nausea,  but  by  a 
decided  increase  of  the  secretions  mentioned  above.  The  vomiting, 
even  when  very  large  amounts  are  taken  into  the  stomach,  is  not  apt  to 
be  severe,  nor  the  prostration  marked. 

The  general  physiological  action  of  ipecacuanha  is  extremely  feeble, 
although  its  alkaloids  are  certainly  very  active  substances.  The  differ- 
ence is  probably  due  to  the  fact  that  ipecacuanha  is  rejected  from  the 
stomach  before  it  can  be  taken  in  sufficient  dose  to  yield  poisonous  amounts 
of  its  alkaloids  to  absorption. 

According  to  D'Ornellas,4  toxic  doses  of  commercial  emetine  cause  in  the  frog 
diminished  sensibility,  muscular  feebleness  deepening  into  abolition  of  voluntary 
movement,  with  at  first  increased  and  afterwards  diminished  activity,  and  finally 
death  from  failure  of  respiration;  in  the  mammal,  similar  symptoms,  with  the  addi- 
tion usually  of  severe  vomiting. 

Nervous  System. — Respiration. — Circulation. — According  to  D'Or- 
nellas and  Pecholier,  commercial  emetine  exerts  no  influence  upon  the 
cerebrum,  but  acts  powerfully  upon  the  motor  side  of  the  spinal  cord, — 
in  the  frog  killed  with  it  both  nerve  and  muscle  retaining  their  suscepti- 
bility to  feeble  galvanic  currents  (D'Ornellas,  Pecholier  and  Foulkrod.5) 
It  causes  death  by  respiratory  paralysis,  which  is  probably  of  centric  origin. 

The  action  of  commercial  emetine  upon  the  circulation  appears  to  be  feeble, 
since  Dyce  Duckworth  has  shown  that  the  fall  of  arterial  pressure  which  the  crude 
alkaloid  produces  does  not  occur  until  late  in  the  poisoning.  The  fall  is  chiefly  of 
cardiac  origin,  as  it  is  prevented  by  previous  section  of  the  spinal  cord  (Foulkrod). 
Moreover,  fatal  immediate  cardiac  paralysis  may  be  caused  in  the  dog  by  injection 
of  half  a  grain  into  the  jugular  vein.  Further,  Lowin  w  has  found  that  pure  emetine 
and  pure  cephaeline  dimmish  the  rate  and  strength  of  the  contraction  of  the  isolated 
frog's  heart,  cephaeline  being  the  feebler  of  the  two  alkaloids.  Psychotrin  had  no 
distinct  effect.  Lowin  also  found  that  both  cephaeline  and  emetine  paralyze  the 
heart  in  warm-blooded  animals. 

*  According  to  Maurel  (Merck's  Bericht,  1901)  the  lethal  dose  of  emetine  on  the 
pigeon  and  rabbit  is  0.15  gramme  per  kilo.  Maurel  also  states  that  emetine  acts  upon  the 
rabbit  as  a  local  anaesthetic. 


EMETICS.  637 

Pulmonic  and  Digestive  Organs. — As  emetine  injected  hypoder- 
mically  causes  vomiting,  ipecacuanha  must  be  looked  upon  as  a  centric 
emetic  ;  but  the  observation  of  D'Ornellas,  that  the  emetine  produces 
vomiting  much  more  slowly  when  thrown  into  the  veins  than  when  given 
by  the  stomach,  indicates  that  the  local  irritant  action  of  the  drug  is  a 
factor  in  the  production  of  emesis. 

The  great  influence  of  the  drug  upon  the  abdominal  viscera  is  further 
shown  by  the  fact,  attested  by  Pecholier,  Dyce  Duckworth,  and  D'  Ornel- 
las,  that  in  emetine-poisoning,  although  there  is  a  distinct  fall  of  tempera- 
ture in  the  mouth  and  on  the  surface  of  the  body,  in  the  intestines  the 
temperature  either  remains  stationary  or,  more  commonly,  rises.  Again, 
the  changes  found  after  death  from  emetine  are  almost  exclusively  in  the 
lungs  and  digestive  organs. 

Pecholier,  in  his  earlier  experiments,  found  great  paleness  of  the  lungs,  with 
intense  hyperaemia  of  the  stomach  and  the  upper  half  of  the  intestines,  but  in  some  of 
his  later  experiments  the  lungs  were  profoundly  influenced.  Dyce  Duckworth  es- 
pecially noted  intense  hyperaemia  of  the  lungs,  which  were  in  some  places  emphy- 
sematous,  but  in  other  portions  collapsed  and  even  affected  with  true  consolidation. 
The  lesions  were  much  less  marked  in  the  intestines  than  in  the  lungs,  which  re- 
sembled very  closely  those  taken  from  the  bodies  of  animals  killed  by  section  of 
the  vagi.  The  pulmonic  lesions  were  found  to  be  most  intense  in  the  rabbit ;  the 
intestinal,  in  the  dog,  cat,  and  guinea-pig.  Magendie  first  observed,  years  ago, 
the  pulmonic  lesions  of  emetine-poisoning,  and  D'Ornellas  has  likewise  recorded 
them,  but  has  also  seen  cases  in  which  ischaemia  of  the  pulmonary  tissue  was  found 
after  death. 

It  is  evident  that  the  commercial  alkaloids  of  ipecacuanha  have  a 
special  influence  upon  the  intestines  and  the  lungs,  but  it  has  been  a 
mystery  why  this  influence  should  vary  so  in  power,  especially  in  regard 
to  the  lungs.  Carl  Lowin  finds  that  the  chemically  pure  alkaloid  produces 
almost  equal  influence  on  the  gastro-intestinal  mucous  membranes;  but 
that,  whilst  cephaeline  acts  violently  upon  the  lungs,  after  death  from  pure 
emetine  no  pulmonic  changes  are  to  be  found.  It  would  seem,  therefore, 
that  the  different  results  obtained  by  earlier  observers  have  depended 
upon  the  alkaloids  they  have  used  being  really  varying  mixtures  of  the 
two  alkaloids. 

THERAPEUTICS. — Whenever  it  is  desired  to  unload  the  stomach  or  to 
act  by  emesis  upon  disease,  without  inducing  much  prostration,  ipecac- 
uanha is  the  best  of  the  emetics.  In  narcotic  poisoning  it  is  less  certain 
than  the  "mineral  emetics,"  but,  as  it  produces  no  irritation  of  the 
stomach,  it  can  be  given  more  freely  than  they  can,  and  is  constantly 
used  as  an  adjuvant  to  them.  It  is  especially  useful  in  the  diseases  of 
children,  never  causing  the  serious  depression  which  tartar  emetic  is  so 
apt  to  produce.  When,  however,  very  violent  emesis  is  desired,  as  in 
membranous  croup,  other  emetics,  such  as  zinc  sulphate,  are  to  be  pre- 
ferred on  account  of  the  greater  force  of  their  action. 

In  sick  stomach  of  nervous  origin,  such  as  occurs  in  pregnancy,  minute 


638  LOCAL    REMEDIES. 

doses  of  ipecacuanha  have  so  often  met  with  success  that  there  can  be  no 
doubt  of  their  value.  One  drop  of  the  wine  in  a  teaspoonful  of  water 
should  be  given  every  fifteen  minutes.  The  use  of  ipecacuanha  as  an 
expectorant  will  be  spoken  of  under  that  heading. 

One  of  the  most  important  uses  of  ipecacuanha  is  in  acute  dysentery, 
all  forms  of  which  have  been  treated  with  it  with  asserted  advantage. 
Its  beneficial  action  is  most  obvious  in  bilious  dysentery  and  in  malignant 
dysentery,  as  is  indicated  by  the  fact  that  its  use  is  most  common  in 
tropical  climates.  In  sthenic  inflammatory  dysentery  it  seems  to  be  less 
available,  although  even  in  this  it  has  been  strongly  advocated.  In  a 
valuable  clinical  paper,  A.  A.  Woodhull 6  brings  forward  strong  evidence 
of  the  value  of  the  remedy  not  only  in  dysentery,  but  also  in  choleriform 
diarrhoeas.  It  has  likewise  been  used  with  great  success  in  hepatic  torpor 
and  other  forms  of  abdominal  glandular  derangement. 

It  probably  influences  not  only  the  intestinal  glands,  but  also  the  liver,  since  Pe- 
cholier *  affirms  that  in  animals  killed  by  it  no  hepatic  glucose  can  be  found.  More- 
over, great  advantage  from  its  use  may  often  be  obtained  in  the  condition  known 
as  biliousness.  In  bilious  dysentery  it  will  often  produce  large  tarry  discharges ; 
a  change  in  the  color  of  the  stools  sometimes  follows  its  use  in  catarrhal  jaundice. 
The  mechanical  effect  of  the  vomiting  induced  by  it  in  these  cases,  however,  must 
not  be  lost  sight  of ;  yet  it  does  not  seem  to  us  sufficient  to  account  for  the  results, 
especially  as  some  observers  state  that  the  effects  noted  are  produced  even  when 
little  or  no  vomiting  occurs.  It  has  been  proved  by  D'Ornellas  and  Pecholier  that 
when  emetine  is  introduced  into  the  circulation  or  into  the  cellular  tissue  it  escapes 
with  the  secretions  of  the  stomach  and  bowels  ;  so  that  the  changes  which  are  pro- 
voked in  these  organs  are  evidently  connected  with  the  elimination  of  the  drug. 

In  1890  Surgeon-Major  Harris8  used  in  dysentery  the  ipecacuanha  root,  de- 
prived of  its  emetine,  with  alleged  excellent  results.  His  paper  has  given  rise  to 
considerable  discussion,  and  Surgeon-Captain  Walsh,9  as  the  result  of  his  experi- 
ments, came  to  the  contrary  conclusion  that  the  value  of  ipecacuanha  in  dysentery 
depends  upon  its  emetine,  and  devised  a  method  of  giving  emetine  in  combination 
with  biniodide  of  mercury,  affirming  that  in  this  combination  the  drug  does  not  pro- 
duce vomiting.  Other  clinicians,  however,  have  confirmed  the  statements  of  Sur- 
geon-Major Harris.  When  the  ipecacuanha  root  has  been  de-emetinized  it  fails 
to  produce  vomiting,  or  causes  only  very  slight  vomiting  ;  and  according  to  the 
clinical  studies  of  Kanthack  and  Caddy,10  it  has  all  the  curative  effects  of  ipecac- 
uanha in  dysentery,  and  does  not  cause  depression.  The  freedom  from  alkaloid  of 
this  so-called  de-emetinized  ipecacuanha  seems  to  us  very  doubtful.* 

As  a  h&mostatic,  ipecacuanha  has  been  recommended  by  Trousseau, 
and  Pecholier  "  asserts  that  in  hcemoptysis  it  is  a  specific,  f  It  has  been 
given  with  asserted  advantage  v&  flooding  after  child-birth,  and  Carrigen11 
asserts  that  it  possesses  oxytocic  powers. 

ADMINISTRATION. — As  an  emetic,  ipecacuanha  is  generally  adminis- 
tered in  powder,  thirty  grains  (2  Gm. )  being  given  every  fifteen  or 
twenty  minutes  until  the  desired  effect  is  produced.  For  a  child  a  year 

*  See  especially  A.  A.  Woodhull  (Atlanta  Med.  and  Surg.Journ.,  1875). 
t  Consult  Pacific  ^fed.  and  Surg.Journ.,  1876. 


EMETICS.  639 

old  the  emetic  dose  is  five  grains  (0.3  Gm.).  Its  action  should  be  aided 
and  hastened  by  large  draughts  of  lukewarm  water.  As  a  nauseant  the 
dose  is  from  two  to  five  grains  (0.13—0.3  Gm. ).  In  dysentery  it  is 
generally  best  to  begin  with  a  full  emetic  dose,  or  with  ten  grains  repeated 
every  half-hour  until  emesis  is  produced.  Two  or  three  hours  after 
vomiting,  fifteen  drops  of  laudanum  should  be  exhibited,  followed  in 
twenty  minutes  by  five  to  ten  grains  of  ipecacuanha  in  pill  form  ;  this 
should  be  repeated  every  two  or  three  hours,  the  amount  of  the  opium 
being  lessened,  and  that  of  the  ipecacuanha  increased,  according  to 
circumstances.  The  object  is  to  have  as  much  of  the  ipecacuanha  re- 
tained as  possible.  Another  plan  is  to  give  larger  doses  (twenty  grains), 
repeated  every  two,  four,  or  six  hours,  mustard  being  applied  to  the 
epigastrium  and  opium  exhibited  as  before  ;  and  it  is  said  that  after  two 
or  three  doses  tolerance  is  established  and  the  drug  retained.  In  India, 
enemata  of  ipecacuanha  are  often  employed,  either  as  a  substitute  for  or 
an  adjuvant  to  its  use  by  the  mouth.  This  treatment  has  recently  been 
imitated  by  Chouppe "  and  others,  and  in  our  own  practice  found  to  be 
satisfactory.  It  undoubtedly  often  succeeds  in  dysentery  and  choleriform 
and  chronic  diarrhoeas,  and  the  gastric  symptoms  are  almost  always 
avoided.  In  chronic  cases  the  repetition  of  the  enemata  sometimes  pro- 
duces so  much  local  irritation  as  to  forbid  their  continuance.  We  have 
been  accustomed  to  give  a  scruple  of  the  powder  with  starch  and  lauda- 
num, repeated  every  four  hours.  A  decoction  of  the  drug  is  to  be  pre- 
ferred, as  probably  causing  less  local  irritation  and  being  more  thoroughly 
absorbed.  To  an  adult,  Chouppe  gives  daily  two  injections  of  a  decoc- 
tion, each  lavement  representing  two  and  a  half  drachms  of  the  drug. 

As  a  counter-irritant,  ipecacuanha  is  rarely  used  in  this  country  ;  but 
in  England  a  liniment  is  employed  composed  of  four  parts  of  the  powder 
to  fourteen  parts  of  olive  oil. 

The  preparations  for  internal  use  are  :  a  syrup  (SYRUPUS  IPECACU- 
ANHA— seven  per  cent.,  U.  S. ),  dose,  as  an  expectorant,  five  to  twenty 
minims  (0.3-1.3  C.c. );  a  wine  (ViNUM  IPECACUANHA — ten  per  cent, 
U.  S.),  emetic  dose,  four  fluidrachms  to  a  fluidounce  (15-30  C.c.); 
and  a  fluid  extract  (FLUIDEXTRACTUM  IPECACUANHA,  U.  S. ),  dose,  as 
an  emetic  for  an  adult,  thirty  drops  (2  C.c. ).  TROCHISCI  IPECACUANHA, 
and  TROCHISCI  MORPHINE  ET  IPECACUANHA,  formerly  official,  were 
used  in  catarrh  of  the  throat  as  a  local  application. 

Emetine  has  been  used  in  doses  of  from  one-twelfth  to  one-sixth  of  a 
grain  (0.005-0.01  Gm. ),  but  it  is  very  harsh  and  without  advantage  in 
its  action. 

APOMORPHIN^E    HYDROCHLORIDUM— APOMORPHINE  HYDRO- 
CHLORIDE.     U.  S. 

Apomorphine,  discovered  by  Matthieson  and  Wright,"  occurs  as  a 
snow-white  powder,  which  is  permanent  when  dry,  but  when  moist  or  in 
solution  soon  becomes  green,  and  finally  almost  black. 


640  LOCAL   REMEDIES. 

General  Effects. — In  man,  apomorphine  acts  as  a  prompt  emetic,  the 
vomiting  being  accompanied  by  no  symptoms  of  such  nature  as  to  be  at 
all  characteristic  of  the  drug,  unless  it  be  excessive  secretion  from  the 
salivary,  nasal,  and  lachrymal  glands.  Very  rarely  great  cardiac  depres- 
sion has  been  produced,  but  there  is  reason  to  suspect  that  this  has  been 
due  to  decomposition  products. 

PHYSIOLOGICAL  ACTION. — Local  Action. — The  soluble  salts  of  apo- 
morphine, when  pure,  are  not  irritant,  and  when  used  hypodermically 
should  not  cause  pain.  They  are  absorbed  with  great  rapidity.  Con- 
cerning their  elimination  we  have  no  definite  knowledge. 

In  frogs,  one  to  five  milligrammes  of  apomorphine  cause  restlessness,  followed 
by  an  increasing  sluggishness  and  muscular  weakness  that  may  end  in  real  or  ap- 
parent death.  In  some  instances  there  are  violent  convulsions,  both  clonic  and 
tonic  in  character.*  Sometimes  recovery  occurs  after  both  respiration  and  cardiac 
action  have  apparently  ceased. 

In  dogs,  one  to  two  milligrammes  cause  vomiting,  without  any  other  decided 
symptoms  ;  after  slightly  larger  amounts,  the  vomiting  is  severe,  and  accompanied 
by  free  salivation  and  muscular  tremblings.  After  very  large  doses,  vomiting  does 
not  occur,  but  a  condition  of  intense  restlessness,  the  animal  jumping,  running, 
howling,  and  champing  constantly.  The  slightest  noise  or  alarm  throws  the  animal 
into  violent  excitement  and  terror  ;  with  pupils  dilated  and  ears  drawn  stiffly  back, 
he  endeavors  to  get  out  of  the  apartment,  and  even  to  climb  the  wall.  After  still 
larger  amounts  (four  or  five  grains),  to  this  excitement  is  soon  added  failing  mus- 
cular strength,  and  the  hind  legs  are  dragged  behind  the  animal  in  his  movements. 
The  respiration  is  exceedingly  hurried,  and  convulsions  are  suddenly  developed. 
The  paresis  and  convulsions  increase,  so  that  the  animal  lies  upon  his  back,  kicking 
wildly  into  the  air,  and  finally  dies  asphyxiated.  Rabbits  cannot  vomit,  but  the 
general  symptoms  produced  by  the  alkaloid  in  them  and  in  cats  are  exactly  parallel 
with  those  just  described  as  occurring  in  the  dog.  Very  small  doses  (ten  milli- 
grammes, Harnack)  suffice  to  kill  the  rabbit.  On  chickens  and  pigeons,  according 
to  C.  David,15  it  acts  very  much  as  it  does  upon  dogs  ;  the  stage  of  excitement  is 
very  marked.  After  death  no  distinct  lesions  are  to  be  found,  unless,  as  Quehl 16 
believes,  there  is  habitually  an  excessive  hyperaemia  of  the  pons  Varolii. 

To  the  therapeutist  the  chief  interest  in  apomorphine  is  in  connection 
with  its  power  of  producing  vomiting  ;  but  before  taking  this  up  we  shall 
briefly  review  what  is  known  in  regard  to  its  general  actions. 

Nervous  and  Muscular  Systems. — The  action  of  apomorphine  upon 
the  cerebrum  seems  to  be  that  of  a  primary  stimulant  delirifacient  and  final 
paralyzant.  The  cause  of  the  convulsions  at  present  cannot  be  consid- 
ered as  determined. f  According  to  Reichert's  experiments,  both  the 
sensory  and  motor  nerves  are  first  stimulated  and  afterwards  paralyzed. 
In  opposition  to  the  experiments  of  Quehl,  Harnack "  found  that  apo- 
morphine directly  affects  the  voluntary  muscles,  and  as  his  experiments 

*  G.  Valentin  (Arch.f.  Exper.  Path.  u.  Pharm.,  xi.  399). 

t  The  only  one  who  has  carefully  studied  them  is  Reichert,  and  his  published  account 
is  self-contradictory.  He  reasons  that  the  convulsions  are  chiefly  spinal,  and  yet  says 
that  in  mammals,  after  section  of  the  spinal  cord,  except  "in  very  exceptional  cases," 
they  are  confined  to  the  anterior  part  of  the  body. 


EMETICS.  641 

have  been  confirmed  by  Reichert,  there  can  be  no  doubt  that  apomor- 
phine  is  a  muscle-poison. 

Circulation. — The  reports  upon  the  action  of  this  drug  on  the  cir- 
culation are  somewhat  discordant.  It  appears  to  be  proved  that  the 
therapeutic  dose  does  not  affect  the  blood-pressure,  but,  contrary  to  the 
statements  of  Seibert,18  Max  Quehl,  and  Bourgeois,19  it  has  been  shown 
by  Harnack  and  by  Reichert w  that  the  toxic  dose  does  lower  the  arterial 
pressure  and  is  a  direct  paralyzant  of  the  cut-out  frog's  heart.  Reichert 
has  shown  that  the  mammalian  heart  is  similarly  affected  by  the  drug, 
and  the  final  fall  of  pressure  must  be  at  least  in  part  of  cardiac  origin. 
Reichert  states  that  preceding  the  fall  of  pressure  there  is  a  distinct  rise, 
which  is  prevented  by  previous  section  of  the  cord,  and  is,  therefore, 
probably  due  to  stimulation  of  the  vaso-motor  centres.  The  pulse-rate 
is  markedly  increased  by  small  and  large  doses  of  apomorphine,  the 
maximum  usually  being  reached  about  the  time  vomiting  is  fairly  estab- 
lished ;  subsequently,  in  poisoning,  the  pulse  falls  below  normal.  Reichert 
believes  the  rise  to  be  due  to  stimulation  of  the  accelerators,  and  the  fall 
to  the  influence  upon  the  heart-muscle. 

Respiration. — Usually  the  respiration-rate  is  increased  by  decided  or 
toxic  doses.  During  the  convulsive  period  of  the  poisoning  the  respi- 
rations become  irregular  and  unequal,  and  they  finally  grow  more  and 
more  shallow  and  infrequent,  until  death  results  from  a  paralysis  of  the 
respiratory  centres.  Both  Harnack  and  Reichert  have  noted  that  in  the 
rabbit  previous  section  of  the  par  vagum  does  not  prevent,  but  rather 
increases,  the  respiratory  acceleration  ;  Reichert  affirms  that  in  the  cat 
and  dog  no  increase  of  the  respiration-rate  occurs  under  the  action  of  the 
drug  if  the  pneumogastrics  have  been  cut. 

Temperature. — The  action  of  apomorphine  upon  the  temperature 
appears  to  be  very  trifling  and  inconstant.  According  to  Ziolkowski," 
the  bodily  heat  usually  falls  after  large  doses  from  o.  i°  to  0.5°  G. 
Moerz  noticed  in  one  man  that  the  temperature  rose  during  the  vomiting 
o.  2° ;  while  Bourgeois  affirms  that  in  man  the  drug  has  no  influence  over 
the  temperature,  and  Reichert  has  seen  in  animals  a  rise  follow  the  hypo- 
dermic but  not  the  intravenous  injection  of  the  alkaloid. 

Emesis. — Gee22  was  the  first  to  announce  that  apomorphine  is  a  cer- 
tain and  prompt  emetic,  producing  but  little  nausea,  and  having  the 
great  advantage  of  acting  in  very  small  dose,  a  tenth  of  a  grain  being 
sufficient,  when  injected  under  the  skin,  to  cause  vomiting  in  ten  minutes. 
The  time  required  for  action  depends  largely  upon  the  amount  of  the 
drug  exhibited.  After  very  small  doses  twenty  minutes  may  elapse  ; 
and  in  Bourgeois's  experiments  0.45  grain  produced  violent  vomiting  in 
less  than  two  minutes.  After  these  large  doses  the  emesis  usually 
recurs  once  or  twice  at  intervals  of  a  quarter  to  half  an  hour.*  The 
vomiting  seems  to  be  of  centric  origin,  as.  Reichert  has  succeeded  in  pro- 
ducing it  when  the  thoracic  aorta  was  tied  so  as  to  prevent  any  of  the 
poison  from  reaching  the  stomach. 


642  LOCAL   REMEDIES. 

THERAPEUTICS — Apomorphine  is  a  safe  and  reliable  emetic,  and  may 
be  used  whenever  it  is  desired  simply  to  empty  the  stomach.  Apo- 
morphine has  a  tendency  in  bronchitis  to  cause  free  secretion,  and  is 
especially  useful  in  the  suffocative  catarrh  of  infants,  when  an  emetic  is  re- 
quired to  get  rid  of  the  bronchial  exudation.  Under  these  circumstances 
it  is  said  not  only  to  act  efficiently  as  an  emetic,  but  also  to  render  the 
mucus  more  copious  and  fluid.  In  the  ' '  drunk  wards' '  of  some  of  the 
Philadelphia  hospitals  for  the  relief  of  acute  debauch  apomorphine  is  pre- 
ferred because  the  subjects  habitually  go  to  sleep  directly  after  the  vom- 
iting ceases.  Tull M  has  found  it  useful  in  acute  chorea. 

Probably  because  it  has  morphine  in  its  name  there  was  at  one  time  a 
rather  wide-spread  belief  that  apomorphine  was  not  a  suitable  emetic  in 
narcotic  poisoning.  In  fact,  however,  narcotics  influence  the  action  of 
apomorphine  only  as  they  do  that  of  every  other  emetic,  and  if  apomor- 
phine has  any  narcotic  influence  it  does  not  interfere  with  its  emetic 
action.  Apomorphine  may,  therefore,  be  used  in  any  poisoning  :  hypo- 
dermically  given,  it  is  often  especially  useful  as  a  reinforcement  of  a  me- 
chanical emetic  exhibited  by  the  mouth. 

ADMINISTRATION. — As  an  emetic,  apomorphine  has  usually  been  ad- 
ministered hypodermically,  in  doses  of  one-tenth  of  a  grain  (0.006  Gm.), 
repeated  every  ten  minutes  until  some  effect  is  induced  ;  but  it  may  be 
exhibited  by  the  stomach  in  double  the  amount.  In  cases  of  severe 
poisoning,  where  time  is  of  great  moment,  it  may  be  well  to  give  as 
much  as  one-fourth  of  a  grain  (0.016  Gm. )  at  a  single  injection.  In 
feeble  persons,  however,  caution  must  always  be  exercised  in  using  it,  as 
one-fifteenth  of  a  grain  has  caused  death  in  seven  minutes  in  an  adult, 
fifty-four  years  old,  suffering  from  chronic  bronchitis  with  marked  em- 
physema.23 The  expectorant  dose  is  one-sixteenth  of  a  grain  (0.004 
Gm. ).  Care  must  be  exercised  in  its  use  in  children.  Loeb24  gave 
hypodermically  0.03  grain  to  an  infant,  thirteen  months  old,  suffering 
from  capillary  bronchitis  :  the  free  vomiting  which  was  induced  left  the 
infant  much  exhausted.  In  a  very  few  cases  apomorphine  has  failed  to 
vomit,  and  even  caused  startling  symptoms  :  so  that  care  should  be  ex- 
ercised not  to  push  the  remedy  too  far.  Carville  affirms  that  three-tenths 
of  a  grain  has  caused  a  syncopal  condition  in  an  adult,  and  Prevost** 
details  a  case  in  which  syncope  and  threatening  collapse  were  apparently 
induced  by  a  very  small  dose.  In  children  especially  must  care  be  exer- 
cised, since,  according  to  Harnack,  the  drug  is  very  liable  to  produce 
collapse.  Greenish  preparations  of  apomorphine  should  not  be  used 
unless  the  dose  be  very  small.  Constantine  Paul  states  that  if  glycerin 
be  used  as  the  sole  menstruum  the  solution  will  keep  three  or  four  days. 
Carville M  affirms  that  glucose  acts  well  as  a  preservative,  and  it  is  also 
asserted  that  a  few  drops  of  muriatic  acid  will  suffice. 

*  For  the  doses  required  to  vomit  various  animals,  see  Gaz.  Med.,  1874,  467. 


EMETICS. 


643 


MECHANICAL  OR  STIMULATING  EMETICS. — The  only  drugs  of  prac- 
tical value  in  this  group  are  mustard  flour  and  zinc  sulphate  ;  copper 
sulphate  being  so  irritant  as  to  be  dangerous,  and  alum  and  other  drugs 
sometimes  used  too  uncertain  in  their  influence. 

Mustard  flour  is  very  prompt  and  even  violent  in  its  action,  and  is  to 
be  used  when  it  is  desired  simply  to  evacuate  the  stomach  rapidly.  As 
it  is  generally  to  be  had  at  once,  it  is  especially  useful  in  such  emergencies 
as  narcotic  poisoning.  Dose,  a  heaped  tablespoonful  in  half  a  pint  of 
water,  repeated,  if  necessary,  in  ten  minutes. 

Zinc  sulphate  is  a  very  sure  emetic,  much  used  in  narcotic  poison- 
ing, especially  with  ipecacuanha  or  apomorphine.  Dose,  thirty  grains 
( 2  Gm. )  dissolved  in  about  two  ounces  of  water  :  it  may  be  repeated 
in  fifteen  minutes,  if  necessary, 


REFERENCES. 


EMETICS. 

T.  SACHER Thesis,  Dorpat,  1893. 

3.  HARNACK   .   .   .   .  A.  E.  P.  P.,  iii.  44. 

3.  KOBERT A.  E.  P.  P.,  XV.  36. 

4.  D'ORNELLAS     .   .  Gaz.  Med.,  1873,  537. 

5.  FOULKROD     .   .   .  P.  M.  T.,  viii.  554. 

6.  WOODHULL    .   .   .  Atlanta  Med.  Surg.  Journ., 

1875- 

7.  PECHOLIER    .  .   .  Gaz.  Med.,  1862. 

8.  HARRIS L.  L.,  1890,  ii. 

9.  WALSH Indian  Med.  Gaz.,  1891. 

10.  KANTHACK  and  CADDY  .  Pract.,  1893. 

11.  PECHOLIER    .  .   .  B.  G.  T.,  xcvii.  49. 

12.  CARRIGEN  .  .   .  .  N.  Y.  M.  J.,  1878,  491. 

13.  CHOUPPE    .  .   .  .  B.  G.  T.,  June,  1874. 

14.  MATTHIESON    and    WRIGHT  .  Proc.    Royal 

Soc.,  xvii.  455. 


15.  DAVID  .  .  . 
:6.  QUEHL     .   . 

17.  HARNACK  . 

18.  SEIBERT  .  . 

19.  BOURGEOIS 

20.  REICHERT  . 

31.   ZlOLKOWSKI 

22.  GEE  .... 


23- 

24.  LOEB      .    . 

25.  PREVOST 

26.  CARVILLE 

27.  KlMURA    . 

28.  LOWIN    . 

29.  TULL     .    . 


.  Gaz.  Med.,  1874,  465. 

In.  Dis.,  Halle,  1872. 

A.  E.  P.  P.,  ii.  291. 

L.  M.  R.,  i.  44. 
.  De  1'Apotnorphine,  Paris, 
1872. 

P.  M.  T.,  x.  no. 

In.  Dis.,  Greifswald,  1872. 
.  St.     Bartholomew     Hosp. 
Rep.,  v.  215. 

N.  Y.  M.  R.,  1877,  664. 
.  S.  Jb.,  civ.  272. 
.  L.  M.  R.,  1875,  183. 
.  G.  H.  M.  C.,  1874,  408. 
.  A.  I.  P.,  1903,  xi. 

A.  I.  P.,  1902. 

N.  Y.  M.  J.,  March  11,1905. 


FAMILY   III.— CATHARTICS. 


PURGATIVES,  or  cathartics,  are  those  drugs  which  are  employed  in 
medicine  to  produce  purgation,  or  catharsis.  The  question  whether  they 
act  by  increasing  the  intestinal  secretions  or  the  peristaltic  movements 
has  been  much  discussed. 

Thiry l  experimented  upon  the  subject  of  catharsis  by  drawing  out  a  knuckle 
of  intestine  through  a  wound  in  the  linea  alba,  cutting  it  free  from  the  remainder 
of  the  gut  without  injuring  its  nerves  or  blood-vessels,  sewing  together  the  distal 
and  proximal  ends  of  the  main  portions  of  the  intestines  so  as  to  reform  a  continu- 
ous tube,  and  then,  after  closing  up  one  end  of  the  knuckle,  forcing  the  other  into 
the  wound  so  as  to  make  an  intestinal  cul-de-sac  which  could  be  studied  through  a 
fistulous  opening.  In  dogs  which  had  recovered  after  this  operation,  Thiry  found 
that  large  doses  of  magnesium  sulphate,  of  senna,  or  of  croton  oil  failed  alike  to 
increase  the  secretion  of  the  separated  piece  of  intestine,  although  they  induced 
violent  purging  ;  further,  that  neither  concentrated  solutions  of  Epsom  salt  nor 
infusion  of  senna,  even  though  kept  in  the  cul-de-sac  for  some  time,  were  able  to 
increase  its  secretion  by  exosmose.  More  recently,  S.  Radziejewski 2  has  made  an 
elaborate  investigation  of  the  subject.  As  the  result  of  a  number  of  very  careful 
analyses,  he  asserts  that  there  is  nothing  to  be  found  in  the  stools  produced  by 
magnesium  sulphate,  calomel,  castor  oil,  croton  oil,  senna,  or  gamboge  to  indi- 
cate that  they  are  anything  besides  the  ordinary  contents  of  the  upper  and  lower 
bowels.  Radziejewski  confirms  the  fact  observed  by  C.  Schmidt,  that  the  stools 
of  purgatives  contain  a  great  deal  of  soda,  but  denies  that  this  proves  that  they  are 
transudations,  asserting  that  the  alkaline  salts  are  derived  simply  from  the  pan- 
creatic fluid.  Radziejewski  also  corroborates  the  confirmation  by  Asp 3  of  the  dis- 
covery of  Moreau,*  that  division  of  the  intestinal  nerves  is  followed  by  free  serous 
exudation  into  the  gut,  but  denies  that  purgatives  act  by  paralyzing  the  vaso-motor 
nerves,  because  croton  oil  injected  into  a  loop  of  intestine  which  had  been  sepa- 
rated by  two  ligatures  from  the  remainder  of  the  gut  caused  both  vomiting  and 
purging.  As  no  emulsifying  substance  was  contained  in  the  intestine,  he  declares 
that  no  absorption  could  have  occurred,  and  that  consequently  the  general  intes- 
tinal disturbance  was  simply  due  to  increased  peristaltic  action,  caused  by  the 
internal  local  irritation  of  the  oil  propagated  along  the  intestines.  The  experiments 
of  Thiry  have  also  been  repeated  by  Radziejewski  with  croton  oil  and  with  mag- 
nesium sulphate,  as  well  as  by  Schiff4  with  aloes,  jalap,  and  sodium  sulphate. 
In  all  cases  the  results  were  the  same  as  those  already  noted  as  obtained  by  Thiry. 
Carrying  his  investigations  still  further,  Radziejewski,  by  forming  intestinal  fistulae 
at  such  positions  as  would  enable  him  to  study  the  rate  of  passage  of  the  intestinal 
contents,  found  that  after  a  dog  is  fed  upon  flesh  the  small  intestine  empties  the 
partially  digested  food  into  the  colon  so  rapidly  and  in  such  quantity  as  to  consti- 
tute, so  to  speak,  a  normal  diarrhoea,  and  that  the  long  delay  in  the  exit  and  the 
hardening  of  the  faeces  occur  in  the  large  intestine.  The  liquid  which  passed  into 

*  Comptes-Rendus,  1868,  Ixvi. ;  also  Asp  (Ludwig's  Arbeiten,  1868). 
644 


CATHARTICS.  645 

the  ascending  colon  agreed  in  all  its  characteristics  with  the  stools  of  purgation. 
Radziejewski  also  asserts  that  he  has  established  by  direct  experimentation  that  the 
peristaltic  movements  of  the  small  intestine  are  affected  very  decidedly  by  drastics, 
and  to  some  degree  by  Epsom  salt,  and  that  in  all  cases  the  large  intestine  is  still 
more  intensely  acted  upon.  Although  these  experiments  are  very  interesting,  it 
cannot  be  allowed  that  they  prove  what  is  affirmed  of  them, — namely,  that  purga- 
tives cause  no  increase  of  intestinal  secretion,  but  only  of  peristaltic  action.  So 
much  violence  to  natural  conditions  is  done  in  the  experiments  after  the  method  of 
Thiry  that  they  seem  to  have  very  little  weight.  The  assertion  of  Radziejewski, 
that  croton  oil  confined  in  a  loop  of  intestine  is  not  absorbed,  is  a  pure  assumption, 
and  his  experiment  does  not  warrant  the  conclusions  drawn  from  it.  The  most 
that  can  be  claimed  is  that  these  various  researches  show  that  increased  peristalsis, 
especially  of  the  large  bowel,  plays  a  more  important  role  in  the  production  of 
diarrhoea. 

The  fact  that  previous  section  of  the  par  vagum  prevents  the  action  of  purga- 
tives* is  opposed  to  the  German  theory,  since  it  is  almost  certain  that  division 
of  the  nerves  of  the  neck  does  not  arrest  peristaltic  movements.  Further,  Armand 
Moreau 5  has  found  that  a  solution  of  Epsom  salt  placed  in  a  knuckle  of  intestine 
isolated  by  means  of  two  ligatures  does  cause  a  serous  exudation  into  it,  and  in 
repeating  M.  Thiry's6  experiments  he  has  obtained  opposite  results.  His  experi- 
ments indicate  three  possible  sources  of  fallacy  in  the  work  of  the  previous  investi- 
gators :  first,  if  the  Epsom  salt  be  not  kept  in  the  intestine  for  a  sufficient  length  of 
time  (some  hours),  no  transudation  occurs  ;  second,  in  some  cases  the  inner  end 
of  the  isolated  piece  of  intestine  fails  to  adhere,  so  that  the  opening  is  not  obliter- 
rated,  and  the  matters  injected  into  the  arrested  cul-de-sac  really  pass  into  the 
peritoneal  cavity  ;  third,  atrophy  of  the  mucous  membrane  and  glandular  apparatus 
of  the  cul-de-sac  often  follows  almost  at  once  upon  the  operation,  and  of  course 
necessitates  a  negative  result  in  the  subsequent  experiments.  Lauder  Brunton,7  in 
a  communication  to  the  Medical  Society  of  London,  states  that  he  has  repeated 
Moreau's  experiments,  and  found  that  magnesium  sulphate  injected  into  the  in- 
testine of  a  cat  caused  about  two-thirds  of  a  drachm  of  fluid  to  be  secreted  in 
four  hours  by  each  inch  of  the  bowel  operated  on,  although  the  proportion  of  sul- 
phate was  only  one  grain  to  an  inch.  In  further  experiments  by  Brunton,8  gam- 
boge, elaterium,  and  croton  oil  gave  results  similar  to  those  of  the  Epsom  salt. 
Vulpian9  has  also  repeated  the  experiments  of  Moreau,  and  found  that  both  mag- 
nesium sulphate  and  jalap  provoke  a  "true  intestinal  catarrh,"  the  vegetable 
cathartic  at  the  same  time  increasing  the  peristaltic  action,  but  the  saline  having  no 
such  effect.  The  experiments  of  Legros 10  and  of  M.  Van  Braam  Houckgeest "  show 
that  salines  do  not  increase  the  activity  of  the  peristaltic  movements,  whilst  those 
of  Matthew  Hay12  are  thought  by  him  to  prove  that  a  saline  purgative  always 
excites  more  or  less  secretion  from  the  alimentary  canal,  depending  on  the  amount 
of  the  salt  and  the  strength  of  its  solution,  and  varying  with  the  nature  of  the  salt. 
To  all  this  evidence  may  be  added  the  experiments  of  Arthur  Clopatt,™  in  which 
various  purgative  dnigs  thrown  into  the  gut  failed  to  increase  the  pressure  in  a 
manometer  which  had  been  introduced  into  a  loop  of  the  intestines  tied  at  both  ends, 
showing  that  they  did  not  increase  the  intestinal  contraction ;  and  also  those  of 
Hess.t  made  by  introducing  into  the  duodenum,  through  a  gastric  fistula,  a  disten- 

*  See  paper  by  H.  C.  Wood  {American  Journal  of  the  Medical  Sciences,  1870,  Ix). 

t  Hess  also  states  that  when,  by  the  blowing  up  of  the  ball  in  the  intestine,  sodium 
sulphate,  castor  oil,  calomel,  senna  leaves,  croton  oil,  and  colocynth  were  prevented 
from  passing  into  the  lower  intestine,  they  failed  to  purge,  although  when  introduced 
below  the  obstructing  ball  by  a  narrow  tube  running  through  it  they  at  once  caused 
diarrhoea.  These  experiments,  if  confirmed,  would  prove  that  the  purgatives  mentioned 
must  come  in  direct  contact  with  the  lower  part  of  the  small  intestine  to  produce  liquid 
stools. 


646  LOCAL    REMEDIES. 

sible  ball,  which  could  be  blown  up  by  the  long  tube  attached  to  it  so  as  to  fill  the 
intestine,  and  noticing  the  rate  at  which  the  ball  moved  under  the  influence  of  a 
peristaltic  movement.  In  these  experiments  it  was  found  that  hydragogues  like 
senna  affected  very  slightly  the  peristalsis,  whilst  drastics  like  croton  oil  had  a  very 
distinct  influence.  J.  Bruce  MacCallum60  believes  that  the  action  of  salines  on 
peristalsis  is  due  to  an  influence  on  the  nervous  system,  and  is  preceded  by  absorp- 
tion, because  he  found  that  the  intravenous  injection  of  certain  saline  substances 
caused  in  the  rabbit  increased  peristalsis  in  from  one-tenth  to  one-fifteenth  of  the 
time  that  is.  required  for  the  action  of  the  same  saline  when  introduced  into  the 
intestines.  Also,  that  only  one-fifth  of  the  intestinal  dose  is  required  intravenously 
to  produce  effect. 

The  experimental  evidence  is  very  far  from  demonstrating  that  in- 
creased peristalsis  is  the  cause  of  the  watery  stools  produced  by  purga- 
tives. The  evidence,  both  experimental  and  clinical,  is  indeed  over- 
whelmingly in  favor  of  increased  secretion.  The  facts  proved  by  clinical 
observations  and  by  experiment — that  purgatives  increase  greatly  the  se- 
cretion in  an  isolated  knuckle  of  intestine,  that  various  purgatives  act 
when  taken  into  the  blood,  and  that  in  these  cases  elimination  by  the 
bowels  occurs  ;  that  at  least  some  purgatives  (Headland14),  when  given 
by  the  mouth,  are  absorbed,  disappearing  from  the  alimentary  canal  and 
reappearing  when  purgation  occurs  ;  that  the  stools  induced  by  overdoses 
of  various  drastics,  as  elaterium,  are  so  enormous  as  to  cause  the  pro- 
foundest  depression,  and  even  choleraic  collapse,  in  a  very  few  hours  ; 
that  the  discharges  caused  by  hydragogues  contain  a  large  percentage 
of  soda,  the  alkali  of  the  serum  ;  that  the  relief  obtained  in  portal  con- 
gestion by  the  depletion  of  salines  is  very  marked — are,  when  viewed 
together,  incompatible  with  any  other  belief  than  that  purgatives  cause 
both  increased  secretion  and  increased  peristalsis  in  the  alimentary 
canal. 

The  question  of  the  action  of  drugs  upon  the  flow  of  bile  is  a  very 
important  one,  the  evidence  concerning  which  is  best  considered  under 
two  headings  :  first,  the  experimental  ;  second,  the  clinical. 

The  experiments  upon  this  subject  which  have  attracted  most  attention  are  those 
of  Scott,  and  of  the  Edinburgh  committee,  of  which  Bennett  was  chairman  and 
Rutherford  and  Gamgee  the  workers.  The  method  employed  both  by  Scott  and 
by  the  Edinburgh  committee  was  to  make  biliary  fistula?  in  dogs  in  the  usual  phys- 
iological manner,  and,  after  recovery  from  the  operation  had  taken  place  and  the 
bile  regularly  escaped  by  the  external  orifice,  to  administer  the  drugs,  especially 
calomel  and  podophyllin,  and  study  the  effects  upon  the  excretion  of  bile.  Of  the 
accuracy  of  their  experiments  we  do  not  think  that  there  can  be  any  reasonable 
doubt.  They  prove  that  in  dogs  with  biliary  fistulae  mercury  has  no  effect  upon  the 
flow  of  bile  unless  given  in  such  quantities  as  to  deteriorate  the  general  health, 
when  it  diminishes  the  biliary  secretion.  The  result  does  not,  however,  warrant 
the  further  conclusion  that  mercury  does  not  increase  the  flow  of  bile  in  healthy 
dogs.  The  animals  were  in  such  an  unnatural  condition  that,  in  spite  of  the  daily 
ingestion  of  much  more  than  the  normal  amount  of  food,  they  progressively  ema- 
ciated, and  finally  died  apparently  of  inanition  :  moreover,  the  innervation  and 
probably  also  the  blood-supply  of  the  liver  was  very  much  interfered  with.  Under 


CATHARTICS.  647 

these  circumstances  it  is  clearly  conceivable  that  the  mercurial  or  other  purgative 
might  in  the  uninjured  dog  affect  the  biliary  secretion,  and  yet  fail  to  do  so  in  the 
experiment,  hindered  by  some  obscure  yet  sufficient  cause.  A.  Rohrig15  experi- 
mented by  a  method  which  simulated  more  closely  the  natural  conditions,  although 
even  the  results  which  he  thus  obtained  do  not  seem  to  us  conclusive.  In  curarized 
dogs  in  which  life  was  maintained  by  artificial  respiration,  he  placed  a  glass  tube  in 
the  gall-duct  so  that  the  bile  could  escape  only  through  it.  Under  these  circum- 
stances, of  course,  after  a  time  secretion  ceased  ;  and  Rohrig  experimented  not  only 
on  the  effect  of  remedies  upon  the  secretion  while  it  was  naturally  going  on,  but  also 
on  their  power  of  re-establishing  it.  He  found  that  large  doses  of  croton  oil  (eigh- 
teen drops)  thrown  into  the  duodenum  caused  an  immediate  very  great  increase,  or 
a  re-establishment,  of  the  secretion.  After  the  oil,  the  vegetable  cathartics  were 
most  active,  decreasing  in  power  in  the  following  order  :  colocynth,  jalap  and  aloes, 
rhubarb  and  senna.  Castor  oil  had  very  little  influence,  as  had  also  the  bitter  salts. 
Calomel,  even  in  large  doses  (twenty  grains),  very  rarely  re-established  the  secre- 
tion, but  its  power  of  increasing  and  maintaining  it  beyond  the  natural  time  for 
cessation  was  very  marked. 

W.  Rutherford  w  used  the  method  of  Rohrig  with  some  improvements.  The 
drug,  mixed  with  bile  to  facilitate  absorption,  was  injected  directly  into  the  duo- 
denum by  means  of  a  hypodermic  syringe.  The  results  obtained  may  be  briefly 
summarized  as  follows : 

Croton  Oil  in  enormous  doses  neither  purged  nor  affected  the  biliary  secre- 
tion. 

Podophyllin  very  greatly  increased  biliary  secretion,  especially  when  in  such 
small  doses  that  it  did  not  purge  severely. 

Aloes  very  greatly  increased  biliary  secretion,  the  doses  used  not  purging 
greatly. 

Rhubarb,  Colchicum,  Iridin,  Colocynth,  Jalap,  Sodium  Sulphate,  Sodium 
Phosphate,  and  Rochelle  Salt  very  greatly  increased  biliary  secretion,  at  the  same 
time  purging. 

Senna,  Taraxacum,  Scammony,  Gamboge,  Castor  Oil,  Magnesium  Sulphate, 
and  Ammonium  Chloride  acted  very  feebly,  if  at  all,  upon  the  liver. 

Leptandrin,  Sodium  Chloride,  and  Potassium  Bicarbonate  had  some,  but  not 
a  powerful,  effect  on  the  liver. 

Ewmymin,  Sanguinarine,  and  Ipecacuanha  exerted  a  very  powerful  influence 
on  the  secretion  of  bile,  and  did  not  purge. 

Calomel  had  no  effect  on  the  biliary  secretion,  but  when  to  it  a  minute  propor- 
tion of  corrosive  sublimate  was  added  the  effect  was  very  marked  ;  Corrosive 
Sublimate  acted  as  a  very  powerful  biliary  stimulant. 

There  is  one  objection  to  the  experiments  of  Rutherford  and  Vignal  entirely 
independent  of  the  method  employed, — i.e.,  there  were  rarely  more  than  two  experi- 
ments with  any  one  substance,  and  in  several  instances  two  experiments  gave  an- 
tagonistic results.  It  is  very  possible,  indeed  probable,  that  if  a  number  of  experi- 
ments had  been  made  with  each  drug,  the  variation  in  results  would  have  been 
much  greater. 

Prevost  and  Binet,  in  their  experiments  with  dogs,  arrange  the  drugs  as  follows  : 

GROUP  I. — Substances  augmenting  greatly  the  flow  of  bile  :  oil  of  turpentine 
and  its  derivatives,  potassium  chloride,  sodium  benzoate  and  salicylate,  salol, 
euonymin,  muscarine. 

GROUP  II. — Substances  slightly  and  inconstantly  increasing  bile  :  sodium  bi- 
carbonate and  sulphate,  sodium  chloride,  Carlsbad  salts,  propylamine,  rhubarb, 
hydrastis. 

GROUP  III. — Substances  lessening  bile  :  potassium  iodide,  calomel,  strychnine. 

GROUP  IV. — Substances  without  action  upon  the  secretion  of  bile  :  sodium 
phosphate,  lithium  chloride,  corrosive  sublimate,  arsenic,  alcohol,  ether,  glycerin, 
quinine,  caffeine,  calumba,  senna,  pilocarpine,  kairin. 


648  LOCAL   REMEDIES. 

Rosenberg  found  that  in  dogs  sodium  salicylate  increased  the  quantity  and 
diminished  the  consistency  of  the  bile  ;  that  turpentine  had  a  slight  stimulant  power; 
whilst  the  Carlsbad  salts  seemed  to  increase  rather  than  decrease  the  biliary  flow. 
Neutral  oils  had  a  much  greater  power  of  stimulating  biliary  secretion  than  any 
other  food  or  drugs,  with  the  single  exception  of  oxgall. 

Stadelmann,67  in  a  series  of  apparently  very  careful  experiments  on  dogs,  found 
that  water,  whether  hot  or  cold,  had  no  influence  upon  the  amount  of  the  fluidity 
of  the  bile. 

Alkalies,  including  the  sodium  chloride,  sulphate,  bicarbonate,  and  phosphate, 
and  many  potash  salts,  artificial  Carlsbad  salts,  Epsom  salts,  and  many  other  alkaline 
salts,  never  caused  any  distinct  increase — indeed,  in  most  of  them  there  was  appar- 
ently a  lessening — in  the  secretion  of  the  liver.  Purgatives,  including  gamboge, 
jalap,  convolvulin,  rhubarb,  aloes,  podophyllin,  calomel,  etc.,  were  equally  without 
distinct  effect.  Diarrhcea  of  itself  had  no  influence  on  the  amount  of  bile.  Atropine 
very  distinctly,  pilocarpine,  alcohol  and  olive  oil  less  distinctly,  lessened  the  flow  of 
bile.  Antifebrin,  antipyrin,  caffeine,  santonin,  and  oil  of  turpentine,  had  a  feeble 
cholagogic  action. 

The  only  substances  which  were  found  to  possess  any  certain  or  powerful  influ- 
ence in  increasing  the  flow  of  bile  were  the  salicylates,  bile  itself,  or  bile  salts. 

The  interpretation  of  this  more  or  less  contradictory  experimental  evi- 
dence is  difficult,  and  its  application  to  practical  medicine  almost  hopeless. 
It  is  apparent  in  the  first  place  that  an  animal  with  a  biliary  fistula  is  not 
in  the  same  position  as  a  normal  animal.  Further,  the  records  of  the 
experiments  show  that  the  secretion  of  bile  in  dogs  having  biliary  fistula 
varies  so  frequently,  so  suddenly,  and  without  apparent  cause,  that 
there  is  always  much  doubt  how  far  the  biliary  condition  which  fol- 
lows the  administration  of  the  drug  is  due  to  that  drug  or  to  some  aiding 
cause.  When  it  comes  to  the  application  of  these  experimental  results  to 
human  medicine,  it  must  be  remembered  that  the  canine  diet  and  digestion 
are  so  different  from  the  human  that  it  is  to  be  expected  that  medicines 
acting  upon  the  digestive  apparatus  will  influence  dogs  differently  from 
man  :  thus,  doses  of  elaterium  that  would  kill  a  man  can  be  given  to  some 
of  the  carnivora  without  causing  the  slightest  purging.  In  view  of  these 
facts,  the  only  fairly  deducible  conclusion,  in  regard  to  the  experimental 
evidence  that  has  been  brought  forward,  is,  that  it  must  be  received  with 
the  greatest  reserve  or  be  entirely  laid  aside  when  we  desire  to  study  the 
question  as  to  the  cholagogic  action  of  remedies  upon  man. 

We  know  of  but  two  experiments  upon  human  beings, — these  having 
been  on  persons  suffering  from  biliary  fistula. 

In  the  one  case  of  human  biliary  fistula,  William  Bain  M  reached  the  conclusion 
that  Kissingen  water,  Carlsbad  water,  euonymin,  sodium  benzoate,  and  sodium  sali- 
cylate increased  both  the  amount  of  bile  and  of  its  solids,  whilst  podophyllin  resin 
increased  the  elimination  of  solids  without  affecting  the  absolute  quantity  of  the 
bile.  In  the  second  case,  Pfaff  and  Balch  w  found  that  the  biliary  secretion  varied 
extraordinarily  and  inexplicably  ;  that  it  was  apparently  not  affected  either  by 
calomel  or  corrosive  sublimate  ;  that  salol  increases  the  watery  flow  and  the  solids 
of  the  bile  distinctly  ;  but  that  oxgall  had  a  very  remarkable  effect,  increasing  the 
amount  of  the  bile  as  well  as  the  percentage  of  its  solid  contents,  the  biliary  acids 
being  especially  thrown  off  in  extraordinary  quantity. 


CATHARTICS.  649 

It  may  well  be  that  the  putting  aside  of  the  gall  bladder,  and  the  other 
conditions  created  by  the  biliary  fistula,  has  a  distinct  influence  upon  the 
liver  ;  certainly  thus  far  experimental  evidence,  both  in  the  lower  animals 
and  in  man,  hardly  coincides  with  clinical  evidence  as  to  the  action  of 
drugs  upon  the  liver  (see  Hydrargyrum,  p.  658),  but  this  apparent  dif- 
ference may  rest  upon  the  different  conditions  of  the  subjects,  as  already 
pointed  out. 

In  regard  to  the  drastics,  there  can  be  little  doubt  that  almost  any 
irritant  purgative  will  to  a  greater  or  less  extent  increase  the  escape  of 
bile,  probably  both  by  increasing  its  flow  into  the  duodenum  and  by 
sweeping  it  out  of  the  small  intestine  before  absorption  can  take  place. 
There  are,  however,  two  actively  purgative  substances  of  which  it  is  es- 
pecially asserted  that  they  are  cholagogues, — namely,  calomel  and  podo- 
phyllin.  The  discussion  of  the  action  of  these  will  be  found  under  their 
respective  headings. 

Violent  purgation,  whether  produced  by  drugs,  poison,  or  disease, 
has  a  distinct  influence  in  checking  the  secretion  of  urine.  In  the  ex- 
periments of  Hugo  Heinrichsen,17  various  vegetable  cathartics  affected 
the  renal  secretion  much  less  than  did  salines,  a  result  probably  due  to 
their  being  less  actively  hydragogue  in  their  intestinal  action.  Hein- 
richsen further  found  that  whilst  the  vegetable  cathartics  do  not  increase 
the  solids  of  the  urine,  the  salines  have  such  influence  ;  but  in  Matthew 
Hay's  experiments  the  amount  of  the  normal  constituents  of  the  urine  was 
not  found  to  be  affected  by  the  salt,  and  it  is  probable  that  the  urinary 
solids  are  increased  only  by  the  weight  of  the  eliminated  saline. 

Various  divisions  of  purgative  medicines  have  been  proposed  by  dif- 
ferent authors,  but  probably  the  most  convenient  arrangement  is  as 
follows  : 

1.  Laxatives. — Medicines  which  simply  unload  the  bowels,  and  are 
not  able  to  cause  active  purgation,  even  when  given  in  very  large  doses. 

2.  Purges. — Medicines  which  purge  actively,  but  are  not  capable  of 
acting  as  poisons,  even  in  very  large  amount. 

3.  Hydragogues  (including  the  Salines),  which  produce  very  large 
watery  stools  without  much  irritation.      In  overdoses,  medicines  of  this 
class  assume  some  of  the  characters  of  those  of  the  next. 

4.  Drastics,  which  cause  great  irritation  of  the  alimentary  mucous 
membrane,  and  in  overdoses  are  violent  poisons. 

It  must  be  borne  in  mind  that  this  classification  is  somewhat  artificial ; 
that  the  effects  of  the  remedies  depend  much  upon  the  doses  in  which 
they  are  administered,  so  that  in  sufficiently  minute  quantity  a  drastic 
may  act  as  a  laxative  ;  and  that  the  dividing  lines  between  the  groups  are 
not  distinct. 

Enemata. — When  it  is  desired  simply  to  unload  the  lower  bowels,  the 
object  can  often  advantageously  be  attained  by  injecting  various  materials 
into  the  rectum,  so  as,  by  mechanical  distention  or  by  irritating  the 


650  LOCAL    REMEDIES. 

mucous  membrane,  to  stimulate  the  peristaltic  action.  The  simplest, 
least  irritant,  and  least  active  enema  is  one  of  cold  water.  In  cases  of 
habitual  constipation,  especially  when  complicated  with  piles,  the  injection 
of  a  pint  of  cold  water  at  a  fixed  hour  daily  often  acts  most  kindly.  The 
ordinary  ' '  opening  injection' '  consists  of  a  pint  of  water  and  a  tablespoon- 
ful,  each,  of  salt,  molasses,  and  soft  soap  ;  castor  oil  is  often  added  to  it, 
and,  if  it  be  desired  to  make  it  very  active,  a  teaspoonful  of  oil  of  tur- 
pentine. 

Large  Enemata. — Except  in  individuals  of  extreme  nervous  irrita- 
bility, there  is  little  difficulty  in  filling  the  large  intestine  with  water,  and 
sometimes  the  fluid  can  even  be  made  to  enter  the  small  intestine.  The 
greatest  gentleness  should  always  be  practised,  a  forcing  syringe  never 
being  used.  The  apparatus  should  consist  of  a  rectal  tube,  and  an  ordi- 
nary india-rubber  tube,  four  feet  long,  fitted  to  the  rectal  tube  and  to 
a  funnel,  india-rubber  bag,  or  other  receptacle.  The  patient  should  lie 
upon  his  back  with  the  hips  elevated,  or  in  the  knee-chest  position,  so 
that  the  pelvis  may  be  much  higher  than  the  shoulder.  The  rectal  tube 
having  been  introduced  into  the  rectum,  the  end  with  the  receptacle 
containing  water  is  to  be  raised  vertically.  It  is  essential  that  the  tube 
be  fitted  with  a  cock,  or  be  pinched,  so  as  to  regulate  the  passage  of  the 
liquid.  In  this  way  from  five  to  nine  pints  are  readily  injected.  Unless 
it  is  especially  desired  to  get  the  effect  of  cold  or  heat  upon  the  intestine, 
the  water  in  the  receptacle  should  be  about  100°  F. 

Large  enemata  are  especially  valuable  as  affording  a  means  of  locally 
treating  the  intestines.  Very  frequently  in  dyspepsia,  chronic  constipa- 
tion, and  other  functional  diseases  of  the  digestive  organs,  the  large  in- 
testine habitually  contains  scybala,  fecal  matters,  acrid  secretion,  or 
other  irritant  substances,  whose  removal  two  or  three  times  a  week  by 
means  of  simple  water  or  water  impregnated  with  half  a  drachm  of  sodium 
bicarbonate  to  the  quart  brings  great  relief.  In  dysentery,  chronic  or 
acute,  and  in  pseudo-membranous  colitis  or  enteritis,  by  means  of  the  large 
enemata,  local  application  can  be  made  to  the  colonic  mucous  membrane. 
In  this  way,  in  acute  dysentery,  water,  antiseptics,  germicides,  bismuth 
subnitrate,  and  other  appropriate  remedies  can  be  used.  In  chronic  dys- 
entery, one  drachm  of  silver  nitrate  dissolved  in  half  a  gallon  of  water  is 
often  of  the  greatest  service. 

As  originally  recommended  by  Mosler,  these  injections  are  sometimes 
very  useful  against  intestinal  parasites.  In  this  way  especially  may  they 
be  used  against  the  oxyuris  vermicularis ,  which  often  inhabits  the  whole 
of  the  large  intestine.  In  bad  cases  of  seat-worm,  the  large  injection 
should  always  be  employed.  In  obstinate  cases  of  tape-worm,  when  the 
worm  has  been  weakened,  and  partially  or  completely  expelled  from  the 
small  intestine  under  the  influence  of  vermicides  given  by  the  mouth, 
filling  the  colon  with  a  medicated  solution  often  brings  success.  Some- 
times a  saturated  solution  of  salt  suffices,  or  quassia  may  be  employed. 
Mosler  records  as  especially  effective  a  tablespoonful  of  chlorine  water 


CATHARTICS.  651 

to  every  pint  and  a  half  of  water.  A.  Rohrig 18  having  found  that  in- 
testinal injections  of  water  have  a  very  great  influence  over  the  secretion 
of  bile,  Mosler  has  been  led  to  try  forced  enemata  in  catarrhal  and  other 
jaundices,  with  asserted  good  results. 

HYPODERMIC  PURGATION. — Apocodeine  is  the  only  known  substance 
which  appears  to  have  practical  value  as  a  purgative  when  given  hypoder- 
mically.  It  seems  to  be  moderately  effective,  producing  soft  but  not 
numerous  or  very  watery  stools:  it  is  probably  not  effective  when  the 
constipation  is  obstinate,  and  not  sufficiently  drastic  or  hydragogue  in  its 
action  to  be  of  value  in  cases  of  severe  diseases  of  the  brain  when  counter- 
irritation  through  the  intestinal  tract  may  be  desired.  From  one-third  to 
one  grain  of  the  hydrochlorate  may  be  injected  with  proper  antiseptic 
precaution. 

According  to  W.  E.  Dixon,61  podophyllo-toxin  given  hypodermically  purges 
actively,  but  produces  severe  local  inflammation  and  sloughing  at  the  point  of  in- 
jection. Apparently  the  first  to  notice  that  apocodeine  had  the  power  of  increasing 
intestinal  peristalsis  was  Guinard.  After  him,  Toy63  determined  that  when  it  was 
given  by  the  mouth  or  hypodermically  it  acted  as  a  laxative  ;  and  Raviart61  and 
Berlin  in  a  number  of  cases  found  the  injection  of  thirty  minims  (2  C.c.)  of  a  one 
per  cent,  watery  solution  of  apocodeine  hydrochlorate  produced  soft  stools  without 
any  other  disturbances  except  some  pain  and  diffused  redness  at  the  place  of  injec- 
tion. W.  E.  Dixon61  determined  by  experiments  upon  the  lower  animals  that 
apocodeine  lessens  blood-pressure  by  dilatation  of  the  blood-vessels  and  increases 
intestinal  peristaltic  action.  Heinze M  has  used  the  remedy  in  a  large  number  of 
cases.  He  finds  the  dose  of  2  c.c.  of  a  one  per  cent,  solution  is  usually  insufficient, 
and  that  the  strength  of  the  injection  may  be  increased  to  two  or  even  three  per 
cent. ;  and  in  the  latter  dose  is  almost  certainly  effective,  in  some  cases  the  effect 
continuing  several  days.  No  narcotic  influence  was  perceptible,  but  in  a  number  of 
cases  there  was  distinct  irritation  at  the  place  of  injection. 

Fronmuller 19  says  that  one  to  three  grains  of  Merck's  aloin  dissolved  in  hot 
water,  administered  hypodermically,  act  as  an  efficient  purge  ;  R.  Kohn  *°  states 
that  in  his  hands  aloin  of  three  different  commercial  varieties,  hypodermically  ad- 
ministered in  ten  times  the  dose  employed  by  Fronmuller,  failed  to  act.  In  1881, 
as  the  result  of  an  elaborate  investigation,  A.  Hiller "  reached  the  conclusion  that 
whilst  there  are  four  purgatives, — namely,  aloin,  cathartic  acid,  and  the  pure  colo- 
cynthin  and  citrullin  of  Merck, — which  are  capable  of  purging  when  given  hypo- 
dermically, they  are  all  too  irritant  for  practical  use  ;  a  conclusion  which  was  con- 
firmed by  Kohlstock.**  According  to  Meyer,  the  irritant  action  of  Barbadoes  aloin 
is  largely  due  to  the  precipitation  in  the  subcutaneous  tissue  of  insoluble  and  ex- 
tremely irritating  crystals  of  the  drug,  and  may  to  a  considerable  extent  be  over- 
come by  the  use  of  formamide  as  a  vehicle.  Kohlstock  affirms  that  aloin  or  ca- 
thartic acid  acts  much  better  when  given  by  rectal  injection  than  when  admin- 
istered hypodermically.* 

*  The  following  formulae  are  recommended  by  Kohlstock  for  rectal  use  :  Acid,  ca- 
thartic, e  senna,  gr.  iii ;  aq.  dest.  gr.  vii ;  natr.  bicarb,  ad  react,  alkalin.,  q.s. — Colo- 
cynthin,  gr.  i ;  alcohol,  gr.  xii ;  glycerin,  gr.  xii. — Citrullin,  gr.  ii ;  alcohol,  gr.  xlix  ;  gly- 
cerin, gr.  xlfcc. — Aloin,  gr.  xv  ;  formamide,  ^\\.  For  rectal  use  a  solution  of  aloin  in 
glycerin  may  be  substituted.  Kohlstock  gives  the  full  purgative  dose  by  the  rectum  as 
— aloin  15  grains ;  cathartic  acid,  6  grains  ;  colocynthin,  0.04  grain  ;  citrullin  0.02  grain. 
Some  of  these  doses  seem  to  us  distinctly  dangerous. 


652  LOCAL   REMEDIES. 

The  indications  to  fulfil  which  cathartics  are  used  are  as  follows  : 

i.  To  unload  the  Bowels. — It  is  not  necessary,  in  a  work  like  the 
present,  to  say  anything  about  the  evil  results  of  retained  fecal  matter, 
but  only  to  point  out  the  methods  of  relief.  Before  this  can  be  done  to 
advantage,  however,  a  summary  of  the  causes  of  constipation  is  required. 
Constipation  may  be  well  divided  into  acute  and  chronic.  Acute  or 
temporary  constipation  is  that  which  occurs  under  special,  transient  cir- 
cumstances, as  in  convalescence  from  acute  disease,  and  in  pregnancy. 
It  is  to  be  relieved  by  the  use  of  laxative  articles  of  diet,  and,  this  not 
sufficing,  by  laxatives  or  purgative  medicines.  It  should  never  be  for- 
gotten that  acute  constipation  is  sometimes  due  to  organic  affections  of 
the  alimentary  canal,  such  as  enteritis  or  intussusception,  or  is  caused  by 
mechanical  obstacles,  such  as  a  hard  foreign  body  or  an  enormous  gall- 
stone. It  is  evident  that  such  cases  are  not  simple  constipation, — that 
the  treatment  required  is  essentially  different  from  that  of  the  latter 
affection,  and  is  various  according  to  the  lesion.  For  the  diagnosis  and 
treatment  of  these  diseases  the  reader  is  referred  to  works  on  the  practice 
of  medicine.  Chronic  constipation  may  be  due  to  sedentary  habits  of 
life  ;  to  habitual  overwork,  especially  of  the  nervous  system  ;  to  a  de- 
ficiency of  intestinal  secretion  and  of  peristalsis,  apparently  natural  to 
the  individual  and  without  obvious  cause  ;  to  long-continued  voluntary 
habit  of  restraining  the  desire  to  go  to  stool  ;  to  lead  or  other  forms  of 
poisoning  ;  and  to  diseases  of  the  nervous  system  producing  a  paralytic 
state  of  the  intestinal  muscular  fibres.  It  is  evident  that  in  the  treat- 
ment of  these  various  forms  of  constipation  due  regard  must  be  paid  to 
the  cause,  which  should  always,  if  possible,  be  removed.  There  are 
also  certain  cardinal  principles  which  apply  to  the  treatment  of  all  forms 
of  chronic  constipation.  They  are  as  follows  : 

A  voluntary  effort  at  defecation  is  to  be  daily  made  at  a  fixed  hour, 
whether  the  desire  exists  or  not. 

Medicines  are  to  be  avoided  as  far  as  possible,  a  sustained  effort 
being  made  to  regulate  the  bowels  by  means  of  diet. 

In  very  many  cases  the  daily  use  of  enemata  of  cold  water,  with 
attention  to  diet,  suffices  to  attain  the  desired  result. 

If  medicines  become  necessary,  as  small  an  amount  as  will  suffice, 
and  the  mildest  drugs,  are  to  be  used.  Purgatives  or  laxatives  are  at 
best  merely  temporary  devices,  and  if  abused  in  costiveness  increase 
the  trouble.  So  far  as  can  be,  the  attempt  should  be  to  produce  a  per- 
manent impression,  an  alteration  of  the  intestinal  glandular  action  or 
peristalsis.  Thus,  when  atony  of  the  muscular  coat  exists,  strychnine, 
or,  according  to  comparatively  recent  experiments  and  clinical  observa- 
tions, Calabar  bean,  may  be  employed  ;  if  the  hepatic  or  other  glands 
are  habitually  torpid,  nitro-muriatic  acid  may  be  administered. 

When  constipation  is  attended  by  low  spirits  and  a  coated  tongue, 
it  is  almost  always  due  to  a  deficiency  of  secretion,  and  may  be  looked 


CATHARTICS.  653 

upon  as  a  form  of  dyspepsia  :  in  such  cases  nitro-muriatic  acid  is  espe- 
cially valuable,  but  sometimes  a  mild  mercurial  course  seems  almost 
imperative. 

A  second  use  of  cathartics  under  the  present  indication  is  to  remove 
offending  materials,  as  indigestible  or  irritant  food,  foreign  bodies,  acrid 
discharges,  etc.  In  many  cases  of  indigestion  with  undue  fermentation 
in  the  alimentary  canal  a  brisk  cathartic  does  great  good  by  producing 
the  expulsion  of  micro-organisms.  The  possible  importance  of  this  is 
shown  by  the  experiments  of  Gilbert  and  Dominici,23  who  found  that  a 
single  dose  of  a  saline  caused  in  a  healthy  man  the  expulsion  of  over  four 
hundred  and  eleven  billion  organisms. 

2.  To  deplete. — On  account  of  the  large  serous  flow  which  they  pro- 
duce,  the   hydragogue    cathartics  when  freely  exhibited   cause   a  very 
decided  general  depletion. 

Local  depletion  by  means  of  cathartics  is  called  for  in  congestion  of 
the  portal  circulation,  as  well  as  in  dysentery  and  other  acute  intestinal 
inflammations.  Under  the  first  of  these  conditions  may,  we  think,  be 
included  without  violence  cases  of  so-called  torpidity  of  the  liver,  which 
will  be  discussed  in  the  article  upon  calomel.  In  acute  intestinal  inflam- 
mations the  salines  are  to  be  preferred  when  depletion  is  desired,  as  they 
produce  large  serous  discharges  and  are  not  irritant. 

3.  To  promote  Absorption. — By  emptying  the  blood-vessels  the  ca- 
thartics  favor  the   absorption   of   the  exuded  fluid  in  general   dropsy. 
For  this  purpose   the  hydragogues,  and    especially  elaterium,  are   the 
best  purgatives.     The  production  of  catharsis  is  the  surest  method  of 
relief  in  general  dropsy,  also  in  ascites ;  in  other  forms  of  local  effusion 
its  effects  are  less   marked.     As,  however,   purgation    is  the  most  ex- 
hausting of  all  the  plans  employed  for  the  cure  of  dropsy,  due  regard 
must  always  be  had  to  the  strength  of   the  patient.      It  is   frequently 
necessary  actively  to   support  or   even   to    stimulate  while  it   is   being 
carried  out. 

4.  To  remilse. — The  long  tract  of  the  alimentary  canal  affords  a  great 
extent  of  surface  upon  which  to  practise  revulsion  in  certain  brain  dis- 
eases, as  in  mania  and  rheumatic  or  gouty  irritation  of  the  cerebrum.    In 
hyperczmia  of  the  brain,  purgatives  do  good  by  depleting  as  well  as  by 
acting  as  revulsives.     The  drastics  should  be  preferred. 

5.  To  eliminate. — It  cannot  be  doubted  that  the  use  of  purgatives 
in  such  diseases  as  fevers  and  cholera,  with  the  idea  of  eliminating  some 
materies  morbi,   rests   simply  upon  a  crude,   unproved,   and  probably 
false  pathology.       In  rheumatic  disease  and  in  gout  it  is  more  prob- 
able that  they  do  good  in  this  way,  although  it  is  by  no  means  certain 
that  the  advantage  derived  from  their  use  is  not  simply  due  to  deple- 
tion.    In  cases  of  retained  renal  secretion,  the  evidence  is  very  decided 
that   they  do   aid   in   expelling   the  products  of   retrograde  metamor- 
phosis. 


654  LOCAL   REMEDIES. 

LAXATIVES. 

As  has  been  already  stated,  constipation  should  always,  when  possi- 
ble, be  overcome  by  laxative  food.  There  are  two  qualities  by  virtue  of 
which  food  is  laxative.  Chief  of  these  is  bulk.  All  aliment  which  con- 
tains a  large  amount  of  innutritious  material  affords  a  large  residuum, 
which,  by  distending  the  intestine,  stimulates  peristalsis.  Contrariwise, 
articles  of  diet  which  are  highly  nutritious  and  afford  but  little  residuum 
are  constipating.  This  holds  good,  more  or  less  strictly,  among  the 
lower  animals.  Thus,  the  flesh-eating  carnivora  are  habitually  consti- 
pated, the  grass-eating  herbivora  very  generally  lax. 

Owing  to  its  containing  so  little  of  the  innutritious  portion  of  the  grain,  the 
finest  white  flour  favors  a  costive  habit,  while  the  "cracked  wheat,"  in  which  the 
whole  grain  is  eaten,  is  laxative, — as  to  a  still  greater  degree  is  bran,  which  is  com- 
posed almost  wholly  of  the  husk  of  the  wheat,  the  least  nutritious  portion  of  it, 
and  therefore  leaves  a  large  residuum  after  digestion.  Cracked  wheat  is  boiled  into 
a  sort  of  jelly-like  mass,  and  eaten  with  cream  and  sugar,  while  bran  is  taken  in  the 
form  of  bran  bread,  bran  crackers,  or  bran  mush.  Unbolted  flour,  containing  the 
whole  of  the  grain,  is  about  equal  to  cracked  wheat,  and  is  often  made  into  bread. 
Indian  meal,  in  the  form  of  cakes  or  of  mush,  is  highly  nutritious  and  somewhat 
laxative ;  oatmeal  is  decidedly  laxative,  scarcely  so  much  so  as  bran,  but  much 
more  nutritious.  When  it  agrees  with  the  stomach,  and  is  digested,  it  is  prob- 
ably the  best  of  all  these  laxative  articles  of  food.  As  the  oats  produced  in  south- 
ern climates  are  very  inferior,  care  should  be  taken  to  procure  oatmeal  manufac- 
tured from  Northern  grain.  It  should  be  thoroughly  cooked,  and  is  best  eaten  in 
the  form  of  a  thick  porridge.  In  dyspepsia  all  of  these  articles  sometimes  disagree 
with  the  stomach  and  cannot  be  used. 

Some  dietary  articles  seemingly  possess  dynamic  laxative  powers, — 
i.e.,  they  exert  a  direct  action  which  is  not  mechanical,  but  is  similar  to, 
although  far  less  active  than,  that  of  the  true  purgatives.  They  intensify 
the  intestinal  action.  Chief  among  substances  of  this  class  are  molasses 
(SYRUPUS  Fuscus)  and  it  scongener,  brown  sugar ;  white  sugar  (SAC- 
CHARUM,  U.  S.)  probably  does  not  share  these  laxative  powers  ;  sugar 
of  milk  (SACCHARUM  LACTIS,  U.  S. )  is  probably  also  nearly  inert.  Of 
course,  great  care  is  usually  necessary  in  taking  advantage  of  the  laxa- 
tive virtue  of  molasses,  on  account  of  the  danger  of  producing  fermenta- 
tion and  acidity  in  the  primae  viae. 

There  are  certain  foods  which  combine  the  two  methods  of  action 
spoken  of.  Chief  among  these  are  the  fresh  acidulous  fruits — such  as 
apples,  pears,  etc. — and  the  dried  fruits.  Of  the  latter,  the  fig  (Ficus, 
U.  S. )  is  one  of  the  most  palatable,  and,  owing  probably  to  the  great 
number  of  small  seeds  which  it  contains,  is  the  most  efficient.  Prunes, 
U.  S. ,  are  as  agreeable  as  figs.  To  a  limited  extent  the  finest  varieties 
of  them  may  be  eaten  raw  ;  but  they  are  especially  to  be  recommended 
stewed.  When  it  is  necessary,  a  pinch  of  senna-leaves  may  be  cooked 
with  them,  so  as  to  increase  their  activity  without  affecting  their  flavor. 

Among  constipating  articles  of  diet,  it  is  only  necessary  to  call  atten- 
tion to  milk  as  one  of  the  most  decided  of  the  class. 


CATHARTICS.  655 

MANNA.  U.  S. — An  exudation  of  the  European  ash,  Fraxinus  Ornus, 
chiefly  produced  in  Sicily  and  Calabria.  The  best  quality,  flake  manna, 
occurs  in  unequal,  rough,  stalactite-like  pieces  with  a  crystalline  or  gran- 
ular fracture.  Manna  has  a  slight  odor,  a  sweet,  mawkish  taste,  and 
should  contain  from  forty  to  eighty  per  cent,  of  the  saccharine,  active, 
crystalline  principle,  manmte,  which  differs  from  ordinary  sugar  in  the 
relation  between  the  amounts  of  hydrogen  and  oxygen,  and  is  not 
readily  convertible  into  grape  sugar  or  its  derivative,  alcohol.  It  is  a 
gentle  laxative,  in  large  doses  sometimes  causing  flatulence  and  pain; 
rarely  used  by  itself,  it  is  often  added  to  purgative  infusions.  The  laxa- 
tive dose  for  an  adult  is  half  an  ounce  to  two  ounces  ( 1 5-60  Gm. ) ;  for  a 
child,  one  to  four  drachms  (4-15  Gm. )  in  an  aromatic  infusion. 

FRANGULA.  U.  S. — The  bark  of  Rhamnus  frangula,  one  of  the  buck- 
thorns of  Europe,  is  considerably  used  abroad  as  a  laxative.  Its  active 
principle  is  a  glucoside,  frangulin ;  a  fluid  extract  (FLUIDEXTRACTUM 
FRANGUL^E,  U.  S. )  is  official, — dose,  ten  to  twenty  minims  (0.6-1.2 
C.c. ).  In  this  country  it  is  employed  very  rarely,  but  the  bark  of 
Rhamnus  Purshiana,  or  California  buckthorn,  is  very  largely  used  under 
the  name  of  Cascara  Sagrada  (RHAMNUS  PURSHIANA,  U.  S. ).  It  con- 
tains a  glucoside,  purshianin,  closely  allied  to  frangulin,  and  often  acts 
most  happily  as  a  laxative  in  habitual  constipation.  Fifteen  drops  ( i  C.  c. ) 
of  the  fluid  extract  (FLUIDEXTRACTUM  RHAMNI  PURSHIAN^E,  U.  S.) 
may  be  given  one  or  two  hours  after  meals,  or  half  a  fluidrachm  (2  C.c.) 
may  be  administered  at  bedtime,  or  of  the  aromatic  fluid  extract  (FLUID- 
EXTRACTUM RHAMNI  PURSHIANA  AROMATICUM,  U.  S.),  one  to  two 
fluidrachms.  The  solid  extract  (EXTRACTUM  RHAMNI  PURSHIANA,  U. 
S. )  is  effective  in  doses  of  two  to  five  grains  (0.13-0.3  Gm. ). 

FEL  Bovis.  U.  S. — The  United  States  Pharmacopoeia  recognizes 
crude  Oxgall,  and  prepares  from  it  by  means  of  alcohol  FEL  Bovis  PURIFI- 
CATUM  {Purified  Oxgall},  a  yellowish-green,  soft  solid,  having  a  peculiar 
odor,  and  a  partly  sweet  and  partly  bitter  taste.  It  is  very  soluble  in  water 
and  in  alcohol.  When  taken  internally  in  large  doses  it  is  a  feeble  laxa- 
tive. There  is  much  experimental  evidence  (see  page  645)  to  show  that 
oxgall  has  marked  influence  upon  the  secretion  of  bile,  and  the  clinical 
evidence  is  strongly  in  favor  of  the  belief  that  in  that  condition  known  as 
chronic  biliousness,  full  doses  of  oxgall  often  act  very  favorably.  We 
have  also  used  it  in  catarrhal  jaundice  with  apparent  excellent  results. 
Dose,  five  to  twenty  grains  (0.33-1.3  Gm. ),  best  given  in  capsule. 

EUONYMUS,  U.  S.,  or  Wahoo,  the  bark  of  Euonymus  atropurpureus,  was  found 
by  Noel  Paton,24  when  given  to  dogs  in  small  dose,  to  increase  greatly  the  elimina- 
tion of  urea  and  uric  acid,  and  by  Rutherford  to  be  in  large  dose  an  active  chola- 
gogue  in  dogs.  In  man  its  effects  are  often  most  happy  in  cases  of  habitual  consti- 
pation and  hepatic  torpor.  It  acts  very  slowly  and  purges  only  moderately.  The 
dose  of  the  extract  (FLUIDEXTRACTUM  EUONVMI,  U.  S. )  is  eight  minims  (0.5  C.c.); 


656  LOCAL   REMEDIES. 

of  its  extract  (EXTRACTUM  EUONYMI,  U.  S. )  the  so-called  euonymin  (the  best  prep- 
aration), two  to  four  grains  (0.13-0.26  Gm.)  :  in  cases  of  dyspepsia  it  may  be 
repeated  with  good  results  two  or  three  times  a  week. 

LEPTANDRA.  U.  S. — The  rhizome  and  roots  of  Veronica  virginica,  when 
given  in  a  fresh  state,  are  apparently  cathartic,  but  in  their  officinal  dried  form  are 
mild  and  less  certain.  They  are  believed  by  various  practitioners  to  have  special 
cholagogue  properties,  and  in  Rutherford's  experiments  upon  dogs  the  impure 
resin  acted  feebly  upon  the  liver.  The  U.  S.  Pharmacopoeia  recognizes  the  fluid 
extract  (FLUIDEXTRACTUM  LEPTANDRUM).  Dose,  one-half  to  one  fluidrachm. 

Leptandrin,  an  impure  resinous  substance  used  especially  by  the  Eclectics,  may 
be  given  in  doses  of  from  one  to  two  grains  (0.065  to  0.13  Gm.). 

TAMARINDUS.—  Tamarind.  U.  S. — The  preserved  pulp  of  the  fruit  of  Tama- 
rindus  Indica,  a  large  tree,  native  of  the  East  and  West  Indies.  In  the  market  it 
occurs  as  adhesive  masses  composed  of  pulp,  membranes,  strings,  and  seeds,  and 
having  a  sweet  acidulous  taste.  It  contains  a  good  deal  of  citric  acid,  much  less 
tartaric  acid,  and  a  little  malic  acid.  It  is  rarely  used  at  present,  but  is  laxative  in 
doses  of  half  an  ounce  to  an  ounce  or  more,  being  eaten  like  preserves,  and  enters 
into  the  confection  of  senna. 

CASSIA  FISTULA.  U.  S. — Purging  Cassia  is  the  dark,  sweetish,  acidulous  pulp 
of  a  hard,  blackish,  cylindrical  pod  produced  by  Cassia  Fistula,  a  tree  of  Egypt 
and  India.  It  may  be  used  as  a  laxative  in  doses  of  half  an  ounce  (15  Gm. ),  but  is 
apt  to  cause  griping.  It  enters  into  the  official  confection  of  senna. 

MAGNESIA— LIGHT   MAGNESIA.     U.S. 
MAGNESIA    PONDEROSA— HEAVY    MAGNESIA.     U.S. 

The  heavy  and  the  light  magnesia  differ  only  in  their  physical  charac- 
ters, the  particles  being  differently  aggregated.  Magnesium  carbonate 
(MAGNESII  CARBONAS,  U.S.)  is  manufactured  by  precipitating  a  solu- 
tion of  magnesium  sulphate  by  one  of  sodium  carbonate.  If  the  two 
solutions  be  concentrated,  the  dense  or  heavy  carbonate  will  fall ;  on  the 
other  hand,  if  the  solutions  be  dilute,  the  precipitate  will  be  a  light  car- 
bonate. Heavy  magnesia  is  obtained  by  calcining  a  heavy  carbonate  ; 
light  magnesia,  by  using  a  light  carbonate.  All  of  these  substances  are 
of  a  milk-white  color,  and  occur  in  powder  ;  the  carbonates  sometimes 
in  very  light  cubical  blocks.  They  are  all  practically  insoluble  in  water, 
freely  soluble  in  dilute  acid,  and  in  the  presence  of  acids  they  all  act  as 
alkalies. 

THERAPEUTICS. — Magnesia  and  its  carbonate  are  antacid  and  laxa- 
tive. For  their  purgative  powers  they  are  probably  dependent  upon  the 
presence  of  acids  in  the  primae  viae,  and  hence  their  effects  vary.  When 
taken  repeatedly  they  are  said  at  times  to  accumulate  in  the  intestines,  and 
should  not  be  used  as  an  habitual  laxative.  They  are  often  given  along 
with  Epsom  salt  or  senna,  on  account  of  their  antacid  properties.  Their 
chief  use  is  in  acute  acid  dyspepsia,  in  sick  headache,  in  diarrhoea  with 
excessive  acidity  in  children,  in  gout,  in  rheumatism,  and  in  various  cu- 
taneous affections, — wherever,  in  a  word,  a  laxative  antacid  is  indicated. 


CATHARTICS.  657 

Dose,  one  drachm  to  half  an  ounce  (4-15  Gm. );  for  a  child  a  year  old, 
from  five  to  twenty-five  grains  (0.3-1.6  Gm.),  according  to  the  effect 
desired. 

SULPHUR. 

Sulphur  is  official  in  three  forms  :  SULPHUR  SUBLIMATUM,  or  Su&- 
limed  Sulphur ;  SULPHUR  LOTUM,  or  Washed  Sulphur ;  and  SULPHUR 
PR^CIPITATUM,  or  Precipitated  Sulphiir.  The  first  of  these  is  made  by 
subliming  sulphur  into  cool  chambers,  and  always  contains  some  sul- 
phuric acid,  generated  during  the  process.  When  freed  from  the  acid 
by  washing  with  warm  water  and  ammonia,  it  constitutes  the  washed  sul- 
phur. The  U.  S.  Pharmacopoeia  directs  the  precipitated  sulphur  to  be 
prepared  by  boiling  lime  and  sulphur  together,  so  as  to  form  calcium 
sulphide,  and  precipitating  this  with  hydrochloric  acid. 

The  sublimed  and  the  washed  sulphur  occur  as  sulphur-yellow,  crys- 
talline powders  ;  the  precipitated  as  a  whitish  powder,  whose  particles 
are  often  coherent  into  friable  lumps.  For  an  account  of  the  various  allo- 
tropic  forms  of  sulphur,  and  its  chemical  properties,  the  reader  is  referred 
to  works  on  chemistry.  It  is  insoluble  in  water,  but  soluble  in  alkaline 
solutions,  alcohol,  the  fixed  and  volatile  oils,  chloroform,  ether,  etc. 

PHYSIOLOGICAL  ACTION. — When  applied  locally,  sulphur  is  almost 
without  influence.  Taken  internally,  it  is  dissolved  to  some  extent  in 
the  alkaline  intestinal  juices  and  absorbed.  It  has  been  detected  in 
the  milk,  sweat,  urine,  and  even  in  the  breath.  It  would  appear  to  suffer 
oxidation  in  the  system  ;  at  least  its  ingestion  is  followed  by  increase  of 
the  urinary  sulphuric  acid  (Regensburger25).  When  in  sufficient  quan- 
tity, sulphur  acts  as  a  mild  laxative,  producing  soft,  semi-liquid,  feculent 
stools,  accompanied  generally  by  much  offensive  flatus  of  sulphuretted 
hydrogen.  It  is  affirmed  that  in  some  instances  the  latter  gas  has  been 
so  freely  generated  and  absorbed  as  to  cause  systemic  poisoning.  Cases 
have  also  been  reported  in  which  the  flowers  of  sulphur  acted  as  an  irri- 
tant poison  ;  but  this,  without  doubt,  has  been  owing  to  their  containing 
a  large  quantity  of  sulphuric  acid.  Its  continued  use  has  probably  some 
effect  upon  nutrition  ;  the  secretions  generally  are  slightly  increased,  and 
some  have  affirmed  that  the  temperature  is  somewhat  elevated  ;  but  the 
truth  of  this  is  certainly  very  doubtful.  The  results  of  clinical  experi- 
ence indicate  that  it  has  an  especial  tendency  to  act  upon  the  skin  and 
mucous  membranes. 

THERAPEUTICS. — As  an  habitual  laxative,  sulphur  has  been  used 
with  asserted  advantage  in  cases  of  hemorrhoids  and  of  chronic  rheuma- 
tism. In  subjects  of  the  latter  disease  it  is  affirmed  that  it  exerts  a  bene- 
ficial alterative  influence,  especially  in  sciatica  and  in  lumbago  and  other 
varieties  of  muscular  rheumatism.  It  has  also  been  employed  as  an 
alterative  in  various  cutaneous  affections  ;  and  in  the  form  of  natural 
sulphur-waters,  used  externally  and  internally,  there  is  much  testimony 
as  to  its  value  in  both  rheumatic  and  skiri  diseases.  It  is  affirmed  by 

42 


658  LOCAL   REMEDIES. 

Doit z6  that  the  natural  sulphur-waters  are  of  very  great  value  in  the 
treatment  of  chronic  syphilis,  as  they  undoubtedly  are  in  chronic  gout 
and  rheumatism.  They  may  be  substituted  by  the  artificial  sulphur- 
water  described  under  the  heading  of  EXPECTORANTS. 

The  known  germicidal  properties  of  sulphur,  and  the  compounds 
which  it  forms,  indicate  that  it  should  have  value  as  an  intestinal  germi- 
cide, and  it  has  been  found  to  be  of  very  great  service  by  the  U.  S.  medi- 
cal officers  in  the  Philippines  in  the  treatment  of  the  chronic  amoeboid 
dysentery  of  that  country.  It  has  also  been  highly  commended  by  Woro- 
schilsky27  in  typhoid  fever.  In  every  case  from  ten  to  fifteen  grains  may 
be  given  in  capsules  every  three  to  four  hours. 

Sulphur  is  very  largely  used  as  a  parasiticide  in  cases  of  itch. 

Tilbury  Fox  recommends  its  application  in  the  following  manner.  He  says, 
"  I  have  applied  to  all  papules  and  vesicles  the  following  ointment :  sulphur,  half  a 
drachm  ;  ammonio-chloride  of  mercury,  four  grains ;  creosote,  four  drops  ;  oil  of 
chamomile,  ten  drops  ;  and  an  ounce  of  lard.  This  is  rubbed  in  night  and  morning 
for  three  days,  especially  to  the  interdigits  and  wrists  ;  the  same  shirt  is  kept  on  till 
the  third  day,  when  it  is  changed  and  a  warm  bath  given.  The  use  of  the  parasiti- 
cide for  two  or  three  days  should  be  followed  by  a  good  washing  and  the  discon- 
tinuance of  the  remedy  for  a  night.  If  the  patient  be  not  troubled  with  itching 
during  the  night,  we  may  conclude  that  the  acari  are  killed,  and  all  we  need  to  do 
is  to  guard  against  the  hatching  out  of  fresh  acari  by  the  light  application  of  our 
parasiticide  once  a  day  to  any  '  pimply'  or  itchy  place  for  a  few  days  longer,  taking 
care  that  the  foul  clothes  are  well  heated  or  scalded.  '  Not  too  strong  and  not  too 
long'  is  my  rule  in  the  use  of  remedies  for  scabies.  The  occurrence  of  red,  rough, 
erythematous  patches  is  a  sign  that  the  remedy  itself  is  creating  disease." 

ADMINISTRATION. — Dose,  as  an  alterative,  ten  to  twenty  grains 
(0.6-1.2  Gm. )  three  times  a  day  ;  as  a  laxative,  one  to  three  drachms 
(4-1 1  C.  c. )  at  bedtime. 

POTASSA  SULPHURATA. — Sulphurated  Potassa  occurs  in  liver-brown  fragments, 
which  form  an  orange-yellow  solution  in  water.  Its  taste  is  acrid,  alkaline, 
and  very  disagreeable.  When  moistened,  it  feebly  emits  the  odor  of  hydrogen 
sulphide. 

Locally  applied,  the  potassium  sulphuret  is  a  very  decided  irritant.  Taken  in 
large  quantities,  it  is  a  violent  corrosive  poison,  and  is  said  to  have  produced  fatal 
gastro-intestinal  inflammation.  In  medicine  it  is  chiefly  employed  externally.  It 
has  been  used  as  a  stimulating  ointment  (half  a  drachm  to  an  ounce)  in  various 
skin  affections,  and  is  also  used  for  the  formation  of  sulphur  baths,  the  strength  of 
which  should  vary,  according  to  the  requirements  of  special  cases,  from  two  to  six 
ounces  of  the  drug  in  thirty  gallons  of  water.  They  should  be  taken  warm,  the 
patient  remaining  in  from  twenty  minutes  to  two  hours,  and  are  said  to  cause  a 
general  excitement,  amounting  in  some  susceptible  persons  to  high  fever.  When 
employed  strong,  they  sometimes  occasion  a  papular  eruption.  They  have  been 
used  in  chronic  rheumatism  and  in  various  scaly  skin  diseases. 

CALX  SULPHURATA.  U.  S. — Sulphurated  Lime. — Commercial  Calcium  Sul- 
phide.— A  mixture  containing  at  least  fifty  per  cent,  of  calcium  sulphide  with  un- 
changed calcium  sulphate.  It  has  been  strongly  recommended  by  Sydney  Ringer, 


CATHARTICS.  659 

by  Duhring  and  others,  for  the  treatment  of  successive  crops  of  boils,*  and  in 
scrofulous  and  other  unhealthy  sores  and  glandular  enlargements  in  children.  It 
probably  affords  a  feeble  and  uncertain  method  of  administration  of  sulphur.  Of- 
cial  dose,  one  grain. 

PURGES. 

OLEUM  RICINI— CASTOR  OIL.     U.  S. 

A  fixed,  nearly  odorless  oil,  of  a  nauseous  taste,  obtained  from  the 
seeds  of  Ricinus  communis  by  expression.  The  seeds  are  slightly 
warmed  before  being  put  under  pressure,  so  as  to  liquefy  their  con- 
tained oil  ;  and  the  crude  oil  obtained  from  them  is  boiled  with  a  small 
amount  of  water,  so  as  to  coagulate  its  albuminous  impurities.  Castor 
oil  is  remarkable  for  being  soluble  not  only  in  ether,  but  also  in  alcohol. 
The  castor-oil  seeds,  or  beans,  as  they  are  commonly  called,  contain  an 
acrid,  violently  poisonous  principle,  Ricin.^ 

PHYSIOLOGICAL  ACTION. — Castor  oil  acts  upon  the  human  organism 
as  a  mild  but  decided  purgative,  producing  copious  fluid  fecal  discharges, 
and  in  overdoses  sometimes  vomiting,  and  always  purging  freely.  The 
bulk  of  the  castor  oil  is  ricinolein,  a  glyceride  of  ricinoleic  acid,  which  ap- 
pears to  be  the  purgative  principle,  and  to  be  absorbed  ;  at  least  Canvane  \ 
affirms  that  in  children  castor  oil  sometimes  purges  when  rubbed  upon 
the  skin  of  the  abdomen,  and  when  taken  into  the  stomach  it  has  been 
known  to  exude  from  the  skin.§  Buchheim,28  although  he  submitted  the 
passages  produced  by  the  oil  to  careful  chemical  manipulation,  failed  to 
detect  it  or  any  derivatives.  According  to  the  experiment  (quoted  by 
Stille")  of  Hale  upon  himself,  half  an  ounce  of  castor  oil  injected  into  a 
vein  produces  malaise,  nausea,  faintness,  anxiety,  and  general  dulness  and 
depression,  without  purging. 

THERAPEUTICS. — On  account  of  the  mildness  of  its  action  and  a 
special  property  of  soothing  an  irritated  bowel,  castor  oil  is  constantly 
employed  whenever  it  is  desired  simply  to  evacuate  the  intestinal  canal  ; 
not  so  much,  however,  in  chronic  constipation  as  when  a  temporary  action 
is  alone  required.  In  various  inflammatory  or  irritative  affections  of  the 

*  Furuncles  appearing  in  successive  crops  are  usually,  perhaps  always,  due  to  local 
infection  of  the  skin,  and  are  to  be  treated  by  bringing  about  a  condition  of  surgical 
cleanliness  of  the  skin  by  the  use  of  weak  solutions  of  corrosive  sublimate,  hot  water  and 
soap,  and  by  other  methods  similar  to  those  used  by  surgeons  for  the  disinfecting  of  their 
hands. 

t  Three  beans  have  caused  death  in  the  adult.  The  symptoms,  which  do  not  usually 
come  on  until  from  two  to  five  hours,  are  severe  abdominal  pain,  violent  vomiting  and 
purging,  which  after  a  time  may  become  bloody,  collapse,  severe  muscular  cramps, 
cold  sweating  skin,  contracted  features,  thirst,  restlessness,  and  small  rapid  pulse. 
After  death,  intense  redness  and  even  abrasion  of  the  stomach  and  of  the  small  intestine 
are  found.  After  the  stomach  and  large  intestine  have  been  thoroughly  washed  out  with 
warm  water,  the  treatment  of  castor  bean  poisoning  is  that  of  toxic  gastro-enteritis, — 
namely,  the  use  of  opium,  leeches,  ice,  demulcent  drinks,  counter-irritation,  etc.  See 
Robert  and  Stillmark  (Arbeiten  Pharmak.  Inst.  zu  Dorpat,  iii.). 

t  See  H.  Meyer  (Arch.  f.  Exper.  Palhol.  u.  Pharm.,  1890,  xxviii.). 

\  Ward's  case  (London  Med.  Gaz.,  x.  377). 


660  LOCAL   REMEDIES. 

alimentary  canal,  castor  oil  is  often  of  the  greatest  service.  This  is  espe- 
cially seen  in  the  acute  diarrhoeas  and  even  in  the  chronic  enteritis  of 
children,  but  also  holds  good  in  the  diarrhoeas  and  dysenteries  of  adults. 
In  chronic  pseudo-membranous  colitis  we  have  seen  very  excellent  results 
from  the  long-continued  daily  use  of  the  oil. 

The  application  of  the  fresh  leaves  to  the  breasts,  combined  with  the 
administration,  three  times  a  day,  of  a  teaspoonful  of  a  fluid  extract  of 
the  leaves,  is  said  to  decidedly  increase  the  secretion  of  milk.  The  dose 
of  the  oil  is  half  an  ounce  to  an  ounce  (15-30  C.c. )  for  an  adult ;  for  an 
infant  a  year  old,  one  to  two  teaspoonfuls  (4-7  C.c.).  In  dysentery  it 
is  sometimes  advantageous  to  give  the  drug  in  small  dose  every  three 
hours  until  a  decided  purgative  operation  is  induced. 

The  repulsive  taste  of  castor  oil  will  sometimes  cause  vomiting  ;  the 
oil  should,  therefore,  be  given  in  soft  capsules,  or  in  some  way  dis- 
guised, as  in  strongly  aromatized  water,  or  in  emulsion.  A  mixture  of 
equal  parts  of  glycerin  and  castor  oil,  with  two  to  four  drops  of  the  oil  of 
cloves  or  cinnamon  to  the  fluidounce,  is  readily  taken  by  most  persons  ; 
especially  if  it  be  given  in  an  ice-cold  spoon,  which  chills  it  into  a  viscid 
mass. 

HYDRARGYRUM.  U.S. 

The  only  preparations  of  mercury  which  are  used  as  purgatives  are 
calomel  and  blue  mass.  Of  these  the  first  is  by  far  the  more  active,  and 
indeed  is  the  only  one  which  can  be  relied  upon  to  purge. 

The  chief  interest  in  the  purgative  action  of  mercurials  centres  in 
the  question  as  to  their  influence  upon  the  liver.  The  evidence  at 
present  derivable  from  experiments  upon  the  lower  animals  has  already 
been  discussed,  and  the  decision  arrived  at  that  it  must  be  rejected.* 

When  calomel  is  given  to  a  healthy  man  in  moderate  purgative 
doses,  green  liquid  stools  are  produced,  which,  after  larger  doses,  are 
replaced  by  brown  passages.  The  color  of  these  passages  has  always 
been  supposed  by  clinicians  to  be  due  to  the  presence  of  bile  ;  but  re- 
cently it  has  been  affirmed  that  the  green  tint  is  owing  to  a  compound 
of  the  mercury  itself.  Although  no  chemical  proof  of  the  presence  of 
the  metal  or  its  salt  has,  that  we  are  aware  of,  been  furnished,  yet  it  can 
scarcely  be  doubted  that  mercury  is  present  in  the  first  passages  produced 
by  calomel. 

The  question,  evidently,  is  not,  Is  mercury  ever  present  in  the  green  stools  ?  but, 
Is  it  always  present  ?  or,  in  other  words,  Is  it  an  integrant  portion  of  them  ?  The 
evidence  is  not  so  abundant  upon  this  point  as  is  desirable,  yet  seems  sufficient  to 
furnish  a  negative  answer  to  the  last  question.  Simon w  and  Golding  Bird,50  in 
careful  analyses,  both  failed  to  detect  the  metal  ;  and,  as  the  recognition  of  mercury 
is  an  exceedingly  simple  chemical  problem,  it  seems  impossible  that  these  chemists 
could  have  overlooked  the  metal  if  it  had  been  present.  Simon's  analysis  was 

*  For  a  very  elaborate  review  of  the  clinical  evidence,  see  Thomas  R.  Eraser's  paper 
in  the  Edinb.  Med.  Jonrn.,  April,  1871. 


CATHARTICS.  661 

performed  upon  the  fifth  stool  after  the  administration  of  a  large  dose  of  calomel. 
The  passage  was  fluid,  perfectly  green,  had  no  fecal  odor,  exhibited  a  mild  acid 
reaction,  and  showed  under  the  microscope  a  great  number  of  mucus-corpus- 
cles and  epithelium-cells.  Ether  extracted  from  the  solid  residue  (obtained  by 
evaporation)  a  considerable  amount  of  fat,  which  had  an  acid  reaction,  contained 
cholesterin,  and  was  colored  by  biliverdin.  All  the  other  substances  which  were 
separated  from  the  stool  by  water  and  alcohol  were  more  or  less  colored  by  bile- 
pigment.  Bilin,  bilifellinic  acid,  and  biliverdin  were  found  in  large  quantity. 

The  most  satisfactory  evidence  is,  however,  that  furnished  by  Miche"a,31  who 
examined  chemically  the  faeces  under  four  different  conditions.  First,  the  spon- 
taneous dejections  of  six  healthy  individuals :  no  bile  was  detected.  Secondly, 
green  stools  of  three  persons  suffering  from  gastro-intestinal  derangement :  bile- 
pigment  was  found  in  one  case  only,  and  in  that  could  not  be  detected  after  per- 
sistent vomiting  had  ceased.  Thirdly,  calomel  having  been  given  to  eight  healthy 
persons,  five  men  and  three  women,  bile  was  readily  demonstrated  in  the  green 
passages  produced  in  all  of  the  subjects.  Fourthly,  saline  and  resinous  purgatives 
were  given  to  five  persons,  but  no  bile  could  be  detected  in  the  liquid  stools. 

To  the  evidence  brought  forward  in  favor  of  the  proposition  that  calomel  given 
to  healthy  men  causes  an  increased  escape  of  bile  from  the  alimentary  canal  may 
be  added  the  conclusive  fact  that  in  some  persons,  whose  idiosyncrasies  render 
them  very  susceptible  to  the  action  of  calomel,  it  produces  not  merely  purging,  but 
also  vomiting  of  bile,  which  is  scarcely  at  all  altered. 

From  the  facts  which  have  just  been  passed  in  review,  the  conclusion 
seems  inevitable  that  mercurial  purgatives  given  to  healthy  persons  cause 
the  escape  of  large  quantities  of  bile  from  the  alimentary  canal.* 

As  is  well  known,  when  from  any  cause  bile  does  not  pass  into  the 
duodenum,  the  stools  become  very  pale,  of  a  peculiar  potter's-clay,  or 
even  white,  color.  Very  frequently  under  these  circumstances,  which 
may  coexist  either  with  diarrhoea  or  with  constipation,  mercurials  will 
modify  the  color  of  the  passages  and  alleviate  or  cure  any  symptoms 
present.  In  many  cases  the  mercurials  are,  of  course,  powerless  to 
effect  the  desired  result ;  but  this  depends  upon  the  cause  being  organic, 
or  of  some  other  nature  not  to  be  overcome  by  a  secretory  stimulant. 

As  mercurials  in  health  increase  the  flow  of  bile  from  the  intestine, 
and  as  they  will  sometimes  re-establish  it  in  disease  when  the  secretion 
has  altogether  ceased  or  has  been  very  materially  diminished,  the  con- 
clusion seems  inevitable  that  mercurials  have  the  power  of  directly  or 
indirectly  increasing  the  secretion  of  bile.  The  only  objection  of  any 
force  to  be  urged  against  this  deduction  is  founded  upon  the  idea  that  the 
drug  simply  increases  peristalsis  in  such  a  way  as  to  cause  the  bile  natu- 
rally in  the  duodenum  to  be  swept  out  instead  of  being  absorbed.  The 
answer  to  this  is  embraced  in  the  following  facts  :  mercurials  often  restore 
the  color  of  the  passages  when  pale  from  arrested  secretion,  often  without 

*  J.  Zawadzky  (Vratch,  1887,  abstracted,  Bull.  TMrap.,  1887),  as  the  result  of  his 
own  researches,  comes  to  the  improbable  conclusion  that  the  presence  of  bile  in  the  stools 
as  the  result  of  the  use  of  calomel  is  due  to  the  antiseptic  property  of  the  mercurial,  the 
bilirubin  being  converted  into  biliverdin,  which  is  prevented  from  undergoing  decompo- 
sition. 


662  LOCAL    REMEDIES. 

producing  diarrhoea;  other  even  more  active  purgatives  fail  to  induce 
the  same  bilious  passages  ;  when  diarrhcea  exists  with  clayey  stools,  the 
change  in  the  color  of  the  passages  caused  by  a  mercurial  may  coincide 
with  an  unincreased,  or  even  a  lessened,  amount  of  liquidity  ;  diarrhcea 
ordinarily  does  not  cause  bile  to  appear  in  the  passages. 

THERAPEUTICS. — A  mercurial  purge  is  especially  indicated  by  the 
congeries  of  symptoms  known  as  biliousness :  a  heavily  coated  tongue, 
bitter,  disagreeable  taste,  severe  headache,  depression  of  spirits,  loss  of 
appetite,  slight  nausea,  and  light-colored  passages.  It  should  be  borne 
in  mind  that  one  or  several  of  these  symptoms  may  be  absent  in  any 
individual  case.  Of  all  single  indications  for  the  use  of  calomel,  the 
occurrence  of  potter1  s-clay-cohrcd  passages  is  the  most  important ;  and 
if  such  stools  exist,  and  do  not  depend  upon  an  organic  cause,  repeated 
small  doses  of  the  mercurial  should  be  given,  whether  there  be  constipa- 
tion or  diarrhcea. 

In  bilious  fever, — i.e.,  malarial  fever  with  congestion  of  the  liver, — a 
mercurial  purge,  or  several  mild  mercurial  purges,  will  often,  by  exciting 
the  action  of  the  hepatic  gland,  be  of  great  service  in  preparing  the  way 
for  or  aiding  in  the  action  of  quinine.  In  catarrhal  jaundice,  mercurials, 
on  the  whole,  offer,  we  think,  the  most  frequently  successful  mode  of  treat- 
ment. It  is  evident  that  in  such  cases  calomel  does  good  not  merely  by 
its  cholagogue  influence,  but  even  to  a  greater  extent  by  its  antiphlogistic 
power,  no  doubt  lessening  the  viscidity  of  the  secretions  and  abating  the 
inflammatory  action  in  the  hepatic  ducts.  In  many  instances  it  is  well  to 
exhibit  the  mercurial  in  purgative  doses  to  start  with  ;  but  the  main  reli- 
ance is  to  be  placed  in  the  continuous  exhibition  of  small  doses  of  the 
drug  until  the  gums  are  rendered  slightly  sore.  Anything  like  profuse 
salivation  is,  of  course,  to  be  avoided.  In  dysentery  of  an  acute  sthenic 
type,  calomel  acts  as  an  antiphlogistic  and  as  an  alterative,  not  only  to 
the  liver,  but  to  all  the  intestinal  glands.  It  is  possible  that  it  acts  also 
as  a  bactericide,  since  N.  P.  Wassilieff S2  has  found  that  although  it  has 
no  effect  in  checking  the  action  of  the  digestive  ferments,  it  has  a  very 
pronounced  influence  in  stopping  putrefactive  changes  in  food  by  killing 
the  organisms  which  produce  such  changes. 

RHEUM— RHUBARB.     U.S. 

The  root  of  Rheum  officinale,  Baillon,  and  other  species  of  Rheum 
growing  in  China,  Chinese  Tartary,  and  Tartary. 

Rhubarb  occurs  in  hard,  irregularly  cylindrical  or  roundish  pieces,  of 
a  brownish-yellow  color  and  peculiar  bitter  taste,  and  imparting  to  the 
teeth  a  sense  of  grittiness,  due  to  the  presence  of  great  numbers  of 
minute  crystals  of  calcium  oxalate.  At  one  time  rhubarb  was  cultivated 
to  a  considerable  extent  in  Europe,  but  European  Rhubarb  is  no  longer 
found  in  our  markets. 

Rhubarb  contains,  besides  a  peculiar  tannic  acid,  chrysophanic  acid, 


CATHARTICS.  663 

emodin*  and  probably  a  third  active  substance,  rhein,  of  Hesse.  Rhein 
and  rhabarbarin,  of  the  older  chemists,  were  complex  bodies. 

PHYSIOLOGICAL  ACTION. — Rhubarb  is  somewhat  stomachic,  tonic, 
actively  purgative,  and,  owing  to  its  tannic  acid,  secondarily  astringent, 
leaving  a  decided  tendency  to  constipation  after  the  primary  purgation. 
Owing  probably  to  its  chrysophanic  acid,  it  gives  a  yellowish  color  to  the 
milk  of  nursing  women  and  to  the  urine.  Rhubarb  urine  is  to  be  dis- 
tinguished from  that  of  jaundice  by  its  becoming  purplish-red  on  the 
addition  of  an  alkali.  Rhubarb  is  asserted  to  affect  chiefly  the  muscular 
coat  of  the  bowels,  and  to  purge  by  increasing  peristalsis  ;  but  we  have 
never  met  with  any  proof  of  this  common  belief. 

THERAPEUTICS. — Notwithstanding  its  astringent  property,  rhubarb  is 
largely  used  as  an  habitual  laxative,  because  it  does  not  impair,  but,  on 
the  contrary,  seems  to  strengthen,  the  appetite  and  the  digestion.  It 
should  not  be  used  in  a  high  sthenic  state  of  the  system,  or  when  deple- 
tion is  necessary,  but  is  very  valuable  when  it  is  desired  simply  to  unload 
the  bowels  in  a  debilitated  subject.  It  is  much  used  in  diarrhoea,  with 
intestinal  weakness  or  relaxation,  to  unload  the  bowels  of  acrid  secretions. 
The  aromatic  syrup  combined  with  an  alkali  is  especially  serviceable  in  the 
summer  bowel-complaints  of  children  when  the  stools  are  greenish  and 
mucous. 

ADMINISTRATION. — Rhubarb  is  seldom  employed  in  powder,  but, 
when  used,  may  be  given  in  pill,  as  a  laxative  in  five  grains,  as  a 
purgative  in  ten-grain  doses.  In  chronic  constipation,  small  pieces  of 
the  root  are  very  often  carried  in  the  pocket  and  chewed  by  the  person 
affected  pro  re  nata.  The  U.  S.  Pharmacopoeia  recognizes  the  follow- 
ing preparations  of  rhubarb:  EXTRACTUM  RHEI, — dose,  five  to  ten 
grains  (0.3-0.6  Gm.);  PILULE  RHEI  COMPOSITE  (two  grains  of  rhu- 
barb, one  and  a  half  grains  of  aloes), — dose,  two  to  four  pills;  PULVIS 
RHEI  COMPOSITUS  (rhubarb  and  magnesia), — dose,  half  a  drachm  to  a 
drachm  (2-4  C.c. );  FLUIDEXTRACTUM  RHEI, — dose,  twenty  to  thirty 


*  Emodin. — The  nature  of  the  active  principles  of  many  of  the  vegetable  purgatives 
is  still  obscure.  Several  of  them — namely,  rhubarb,  senna,  aloes,  frangulin,  and  cascara 
sagrada— are  believed  by  some  chemists  to  owe  their  properties  to  the  presence  of  anthra- 
cene compounds.  Such  compounds  are  usually  glucosides.  Of  these  compounds  at- 
tention has  been  recently  especially  drawn  by  Tschirch  to  emodin  (trioxymethylantura- 
guinone),  as  being  the  real  active  principle  of  the  class.  The  great  difficulty  is  to  tell 
how  far  a  principle  obtained  by  chemists  from  one  of  these  drugs  originally  exists  in  the 
drug  and  how  far  it  has  been  formed  by  the  decomposition  of  some  other  principle. 
Thus,  chemists  of  repute  affirm  that  emodin  is  a  decomposition  product  from  frangulin ; 
whilst  Tschirch  believes  that  many  of  the  drugs  named  owe  their  great  activity  to  the 
presence  in  them  of  substances  produced  by  the  decomposition  or  change  in  emodin. 

Emodin  has  been  used  to  some  extent  as  a  laxative  in  doses  of  one  to  two  grains.  In 
view  of  the  fact  that  there  is  only  two  per  cent,  of  aloe-emodin  in  Barbadoes  aloes,  about 
two  per  cent,  of  rhubarb-emodin  in  rhubarb,  and  in  senna  a  still  smaller  percentage  of 
emodin,  it  seems  certain  that  emodin  does  not  fully  represent  the  various  drugs.  The 
experiments  of  Asher,  upon  which  Tschirch  based  the  theory  that  in  the  emodin  group 
the  irritation  is  caused  by  the  local  stimulation  of  the  nerve-endings  in  the  intestinal 
mucous  membrane,  with  a  consequently  reflexly  excited  peristalsis,  were  not  sufficient  in 
number  or  thoroughness  to  establish  the  correctness  of  the  theory. 


664  LOCAL    REMEDIES. 

minims  (1.2-2  C.c. )  ;  SYRUPUS  RHEI,  ten  per  cent, — dose,  for  an  infant, 
a  fluidrachm  (4  C.c.)  ;  SYRUPUS  RHEI  AROMATICUS, — dose,  for  an 
infant,  a  fluidrachm  (4  C.c.)  ;  TINCTURA  RHEI,  twenty  percent., — dose, 
one  to  two  fluidrachms  (4-7  C.c. )  ;  TINCTURA  RHEI  AROMATICA,  twenty 
per  cent., — dose,  one-half  to  one  fluidrachm  (2-4  C.c.)  ;  MISTURA  RHEI 
ET  SOD^E  one-and-one-half  per  cent., — dose,  one-half  to  one  fluid  ounce 
(15-30  C.c. ).  The  aromatic  preparations  are  of  pleasant  taste  and 
efficient,  and  are  much  used  for  children. 

ALOE— ALOES.     U.  S. 

Aloes  appears  to  have  been  first  produced  in  the  Island  of  Socotra,  as 
far  back  as  the  time  of  Alexander  the  Great,  333  B.  C. ;  and  the  U.  S. 
Pharmacopoeia  of  1 890  recognized  Socotrine  and  Barbadoes  aloes,  besides 
which  a  variety  of  aloes  produced  at  the  Cape  of  Good  Hope,  Cape  aloes, 
largely  occurred  in  commerce.  At  present,  under  the  general  name  of 
Aloe,  the  Pharmacopoeia  recognizes  simply  aloes,  allowing  the  pharmacist 
to  use  any  form  of  aloes  which  conforms  to  the  standard  given  in  the  text 
of  the  Pharmacopoeia.  Aloes  is  not  now  produced  at  Barbadoes,  while  the 
Socotrine  aloes  occurs  in  the  American  market  only  in  small  quantities, 
the  mass  of  the  commercial  drug  being  produced  in  the  Island  of  Curafoa. 

Aloes  is  obtained  by  cutting  off  the  thick,  succulent  leaves  of  va- 
rious species  of  the  genus  aloe,  allowing  the  juice  to  drain  into  skins, 
troughs,  or  other  vessels,  and  afterwards  inspissating  either  by  exposure 
to  the  sun  or  by  means  of  artificial  heat.  The  aloes  are  blackish-brown 
or  yellowish-brown,  of  a  bitter,  nauseous  taste,  often  with  a  smooth 
fracture,  and  in  the  best  varieties  with  garnetty  edges;  they  yield  their 
virtues  to  alcohol,  imperfectly  to  water,  and  very  imperfectly  to  alkaline 
solutions. 

T.  and  H.  Smith  M  in  1850  discovered  in  Barbadoes  aloes  a  crystalline 
principle, — aloin, — which  was  shortly  afterwards  found  by  Pereira  to 
exist  already  crystallized  in  the  sap  of  various  species  of  aloe-plants,  and 
was  subsequently  obtained  by  Groves*4  from  Socotrine  aloes.  Aloin 
crystallizes  from  its  watery  solution  in  sulphur-yellow  granules,  from  a 
hot  alcoholic  solution  in  star-like  groups  of  needles.  It  is  neutral,  odor- 
less, of  a  taste  at  first  sweetish,  afterwards  intensely  bitter  ;  is  soluble 
with  difficulty  in  cold  water,  freely  in  boiling  water  and  in  alcohol.  There 
are  three  varieties  of  aloin, — barbaloin,  socaloin,  and  nataloin,  obtained 
respectively  from  the  Barbadoes,  the  Socotrine,  and  the  Cape  aloes. 
Aloinum,  U.  S. ,  is  the  aloin  derived  from  Barbadoes  aloes  or  from  Soco- 
tra or  Zanzibar  aloes.  The  aloin  of  commerce  is  chiefly  barbaloin,  and 
is  certainly  an  active  cathartic  in  doses  of  half  a  grain  to  a  grain. 

H.  Meyer  K  finds  that  the  Barbadoes  and  Curacoa  aloin  act  both  on  man  and 
on  many  lower  animals  as  a  purgative,  whilst  the  Natal  aloin  fails  ordinarily  to 
affect  man,  although  it  is  a  certain  cathartic  in  dogs  and  cats.  The  time  required 
for  the  Barbadoes  aloin  to  produce  purgation  was  from  eight  to  thirty  hours,  which 
Meyer  believes  to  be  due  to  the  fact  that  its  physiological  action  depends  upon  its 


CATHARTICS.  665 

undergoing  chemical  change  in  the  intestines.  In  order  to  facilitate  this  change  he 
exhibited  with  it  potassium  carbonate  and  ferrous  sulphate,  and  found  that  these  salts 
markedly  hastened  the  effect.  He  also  found  that  Natal  aloin,  when  given  to  per- 
sons who  had  been  fed  for  six  days  an  exclusively  animal  diet,  acted  as  a  cathartic.* 
In  the  lower  animals  Kohn  **  found  the  hypodermic  injections  of  aloin  to  cause 
gastro-enteritis  with  albuminous  urine,  and  a  peculiar  inflammation  of  the  kidneys  ; 
o.i  gramme  of  Merck's  aloin  for  every  kilogramme  of  bodily  weight  was  a  fatal 
dose  for  the  dog.  Aloin  could  be  detected  in  the  urine.  ( Method  of  analysis  given. ) 
Brandenburg S7  has  experimentally  shown  that  very  large  doses  of  aloin  cause  in 
the  rabbit  a  fatal  necrosis  of  the  renal  epithelium  ;  small  doses  produce  a  paren- 
chymatous  nephritis. 

PHYSIOLOGICAL  ACTION. — Aloes  is  a  stomachic,  stimulant  cathartic, 
remarkable  for  the  slowness  of  its  action.  It  has  been  supposed  to 
influence  chiefly,  if  not  solely,  the  large  intestine,  and  the  clinical  evi- 
dence is  very  strong  that  in  overdoses  it  produces  irritation  of  the  rec- 
tum. The  belief,  formerly  universal,  that  it  is  capable  of  producing 
hemorrhoids,  and  the  statements  that  its  habitual  use  in  large  doses 
causes  tenesmus,  a  feeling  of  weight,  heat,  and  uneasiness  in  the  pelvis, 
and  occasionally  excitation  of  the  sexual  organs,  are  of  very  doubtful 
correctness.  Aloin  has  been  detected  in  the  urine  by  J.  Dietrich M  and 
also  by  Meyer. 

THERAPEUTICS. — Aloes,  being  a  stimulating  purgative,  is  chiefly  used 
in  the  constipation  of  atonic  subjects.  In  the  constipation  of  plethora  it 
should  not  be  employed  ;  neither  should  it  be  administered  when  active 
abdominal  or  rectal  inflammation  exists.  During  pregnancy  it  is  best 
avoided,  and  large  purgative  doses  should  never  be  given.  Formerly  it 
was  taught  that  aloes  should  not  be  used  in  hemorrhoids ;  but  most,  if 
not  all,  of  the  cases  of  this  affection  depend  upon  a  condition  of  relaxa- 
tion of  the  rectal  veins,  and  Fordyce  Barker M  insists  upon  the  great 
value  of  aloes  in  piles,  and  states  that  Oppolzer  was  especially  famous 
for  his  treatment  of  this  affection,  and  that  his  prescriptions  were,  when 
piles  are  associated  with  constipation,  aloes  and  quinine  ;  without  con- 
stipation, aloes  and  sulphate  of  iron.  For  bleeding  piles  he  used 
R — Ferri  sulphat. ,  9i ;  Ext.  aloes  aq. ,  3} ;  Ext.  taraxaci,  q.  s.  Ft.  pil. 
no.  60.  S. — One  morning  and  evening,  and  increase  to  three  a  day  if 
necessary.  When  costiveness  accompanies  atonic  amenorrhcea,  aloes 
alone  of  all  the  laxatives  should  be  exhibited  ;  and  it  is  also  of  service  in 
atonic  menorrhagia. 

ADMINISTRATION. — As  aloes  often  contains  sticks  and  other  extrane- 
ous matters,  the  U.  S.  Pharmacopoeia  directs  that  an  ALOE  PURIFICATA, 
or  Purified  Aloes,  should  be  made  by  dissolving  the  crude  drug  in  alcohol, 
straining,  and  evaporating.  Of  this  the  full  purgative  dose  is  ten  to 
twenty  grains  (0.6—1.2  Gm. ).  The  official  preparations  of  crude  aloes 
have  been  almost  entirely  superseded  by  aloin. 

*  Consult  Chem.  Gaz.,  1851  ;  Die  Pflanzenstoffe,  1047  ;  Trans.  Brit.  Pharm.  Soc.,  1872 ; 
Brit.  Med.Journ.,  1887,  i.  747;  Bull.  Thfrap.,  xci.  259;  Land.  Med.  Record,  1877,  459; 
and  Edin.  tfed.  Journ.,  xx.  1002. 


666  LOCAL    REMEDIES. 

The  tincture  (TINCTURA  ALOES — ten  per  cent.,  U.  S. ),— dose,  as  a  laxative, 
one  to  three  teaspoonfuls;  the  tincture  of  aloes  and  myrrh,  ELIXIR  PROPRIETATIS 
(TINCTURA  ALOES  ET  MYRRH.* — aloes  and  myrrh,  of  each  ten  per  cent.,  U.  S. ), — 
dose,  as  a  laxative,  one  to  two  teaspoonfuls;  EXTRACTUM  ALOES,  U.  S., — dose, 
t\vo  grains;  the  pills  (  PILULE  ALOES,  U.  S. ),  each  two  grains  of  aloes;  the  Pills 
of  Aloes  and  Mastich  (PILULE  ALOES  ET  MASTICHES,  U.  S. ),  the  famous  Lady 
Webster  Dinner- Pill,  each  containing  two  grains  of  aloes;  the  Pills  of  Aloes  and 
Myrrh  (  PILULE  ALOES  ET  MYRRHS,  U.  S. ),  used  in  amenorrhcea,  and  containing 
two  grains  of  each  ingredient  in  every  pill;  the  Pills  of  Aloes  and  Iron,  formerly 
official,  contained  each  one  grain  of  aloes  and  one  grain  of  dried  ferrous  sulphate. 
The  Compound  Laxative  Pills  (  PILULE  LAXATIVE  COMPOSITE  U.  S.),  A.  B.  S. 
pill  of  the  drug  stores, — aloin,  grain  one-fifth  ;  strychnine,  belladonna  extract, 
ipecacuanha, — is  a  very  efficient  and  popular  combination  in  the  treatment  of  chronic 
constipation,  and  has  justly  received  recognition  in  the  U.  S.  Pharmacopoeia.  One 
or  two  pills  may  be  given  at  a  dose. 

Aloin  is  actively  purgative  in  dose  of  half  a  grain  (0.03  Gm. );  laxa- 
tive dose,  one-fourth  of  a  grain  (0.016  Gm.). 

SENNA— SENNA.     U.  S. 

Under  the  name  of  Senna  various  species  of  the  genus  Cassia  have 
found  their  way  into  commerce,  but  at  present  the  U.  S.  Pharmacopoeia 
recognizes  only  the  leaflets  of  the  Cassia  acutifolia  of  Nubia  and  Upper 
Egypt  {Alexandria  Senna),  and  of  the  Cassia  angustifolia  of  Southern 
India  (  Tinnevelly  Senna}.  The  senna-leaves  vary  from  three-fourths 
of  an  inch  to  an  inch  and  a  half  in  length,  and  are  to  be  distinguished 
by  the  inequality  of  their  bases,  the  two  sides  of  the  lamina  or  leaf- 
blade  joining  the  midrib  at  unequal  heights  and  angles.  Alexandria 
Senna  is  characterized  by  the  presence  of  the  shorter  argel-leaves,  with 
equal  bases,  by  the  ovate-pointed  leaflets  of  Cassia  acutifolia,  and  by 
the  scattered  mucronate-obovate  leaflets  of  C.  obovata.  India  Senna 
is  distinguished  by  the  oblong  leaflets,  from  one  to  two  inches  in  length, 
entire  and  perfect.  Owing  probably  to  the  fact  that  it  is  largely  culti- 
vated in  the  southern  portion  of  the  peninsula  of  Hindostan,  especially 
near  Tinnevelly,  this  senna  at  present  constitutes  the  greater  part  of  that 
which  is  sold  in  the  drug-stores.  Cathartic  Acid,  discovered  by  Dragen- 
dorff  and  Kubly,40  is  its  chief  active  principle.  According  to  Groves, 
four  grains  of  the  ammonium  cathartate  will  purge  actively,  whilst  R. 
Stockman 41  has  shown  that  rabbits  may  be  purged  to  death  by  a  cathartate 
given  by  the  mouth,  although  these  salts  have  no  effect  upon  the  animal 
when  injected  into  the  blood  or  given  subcutaneously. 

THERAPEUTICS. — Senna  is  a  very  powerful,  somewhat  irritating 
hydragogue  cathartic,  acting,  it  is  said,  as  readily  upon  swine,  dogs, 
cats,  and  horses  as  upon  man.  When  given  alone,  it  is  very  apt  to 
gripe  severely,  and  is  consequently  more  often  used  in  combination.  In 
obstinate  fecal  accumulation  the  Black  Draught  constitutes  a  most  efficient 
and  safe  remedy. 

In  small  doses  it  is  often  used  as  a  laxative.     Its  infusion  injected  into 


CATHARTICS.  667 

the  veins  is  said  to  cause  both  vomiting  and  purging,  and  the  milk  of 
nursing  women  taking  it  is  affirmed  to  act  as  a  cathartic.  An  aromatic 
should  be  administered  with  senna,  to  lessen  its  tendency  to  gripe.  The 
leaves  are  not  given  in  substance.  The  dose  of  the  fluid  extract  (FLUID- 
EXTRACTUM  SENN^E,  U.  S. )  is  two  fluidrachms  to  half  a  fluidounce 
(8-15  C.c. )  ;  the  confection  (CoNFECTio  SENN^E,  U.  S. ,  ten  percent.) 
is  a  very  complex  but  elegant  preparation,  used  only  as  a  laxative,  in 
doses  of  one  to  two  drachms  (4—7  C.c.),  especially  in  pregnancy ;  it  is 
not  suited  to  dyspeptic  cases,  on  account  of  its  tendency  to  derange  the 
digestion.  INFUSUM  SENN^E  COMPOSITUM,  six  percent.,  U.  S.  {Black 
Draught},  contains  manna  and  magnesium  sulphate, — an  efficient  hydra- 
gogue  purge,  causing  very  large  watery  discharges  when  given  in  dose  of 
four  fluidounces  (120  C.c.)  ;  the  dose  of  the  syrup  (SVRUPUS  SENN^E — 
twenty-five  per  cent.,  U.  S. )  is  one  to  four  fluidrachms  (4-15  C.c.)  ;  the 
PULVIS  GLYCYRRHIZ.E  COMPOSITUS,  U.  S.,  or  Compound  Licorice 
Powder,  is  an  excellent,  pleasant  laxative  in  doses  of  thirty  to  sixty  grains 
(2-4  Gm. ). 

SALINES. 

MAGNESII  SULPHAS.  U.  S. — Magnesium  Sulphate. — Epsom  Salt  ordi- 
narily occurs  in  small,  acicular,  slowly  efflorescent  crystals,  containing 
about  fifty-one  per  cent,  of  water  of  crystallization,  soluble  in  their  own 
weight  of  water  at  ordinary  temperatures.  The  taste  is  bitter,  saline, 
and  nauseous. 

PHYSIOLOGICAL  ACTION. — Epsom  salt  is  a  most  active  hydragogue 
cathartic,  producing  very  large  watery  discharges  without  causing  any 
irritation  of  the  intestines.  The  soluble  magnesium  salts  injected  into 
the  blood  are  powerful  poisons,  causing  death  by  failure  of  respiration, 
and  also  depressing  the  heart  (J.  H.  Recke,42  also  M.  Hay).  These 
effects,  are,  however,  never  perceptible  in  the  ordinary  use  of  the  mag- 
nesium sulphate,  but  recorded  cases  show  that  the  drug  is  capable  of 
acting  as  a  violent  general  poison.  Christison  reports  a  boy,  ten  years 
old,  killed  by  two  ounces,  without  the  induction  of  purgation.  W.  Sang  ** 
reports  as  caused  by  four  ounces  of  Epsom  salt  in  a  very  concentrated 
solution,  burning  pain  in  the  stomach  and  bowels,  great  dyspnoea,  and 
collapse,  with  dilated  pupils,  muscular  relaxation,  and  finally  coma,  end- 
ing in  death,  without  purging  or  vomiting.  In  J.  H.  Neale's  case  the 
symptoms  were  violent  enteritis,  with  most  alarming  heart  depression, 
from  which,  however,  the  patient  recovered.  In  the  researches  of  Curci," 
it  was  found  that  the  soluble  magnesium  salts  first  increase  the  blood- 
pressure  and  slow  the  pulse,  and  then  lower  the  blood-pressure  and 
quicken  the  pulse,  causing  finally  cardiac  paralysis.  As  the  rise  of  the 
arterial  pressure  is  prevented  by  previous  destruction  of  the  vaso-motor 
centres,  it  is  probably  the  result  of  centric  stimulation.* 

*  The  action  of  the  saline  purgatives  upon  the  tissue-changes  of  the  body  has  been 
laboriously  investigated  by  a  large  number  of  chemists,  with  results  which  are  so  dis- 


668  LOCAL    REMEDIES. 

Epsom  salt  is  very  largely  used  when  it  is  desired  to  deplete  or  to 
promote  absorption  through  the  bowels,  as  in  dropsies  ;  or  to  relieve  con- 
gestion of  the  bowels  themselves,  as  in  enteritis  or  colitis  ;  or  when  it  is 
necessary  to  soften  down  fecal  accumulation,  as  in  obstinate  constipation. 
The  dose  is  half  an  ounce  to  an  ounce  (15-30  Gm.),  properly  diluted. 
M.  Luton45  affirms  that  ten  centigrammes  (1.53  gr. )  administered  hypo- 
dermically  usually  provoke  several  watery  stools  ;  but  the  practice  seems 
to  us  a  very  doubtful  one. 

The  Pharmacopoeia  now  recognizes  an  Effervescent  Magnesium  Sul- 
phate (MAGNESII  SULPHAS  EFFERVESCENS)  which  represents  fifty  per 
cent,  of  the  salt.  This  is  intended  to  replace  the  formerly  official  Effer- 
vescent Magnesium  Citrate,  and  offers  a  pleasant  form  of  administering 
magnesium  sulphate. 

LIQUOR  MAGNESII  CITRATIS.  U.  S. — Solution  of  Magnesium  Citrate 
is  prepared  by  putting  into  a  strong  bottle  a  syrupy  solution  of  magne- 
sium citrate  containing  an  excess  of  citric  acid,  adding  potassium  bicar- 
bonate, and  corking  tightly.  On  account  of  its  agreeable  taste  and 
effervescence,  this  preparation  is  much  used  as  a  purgative.  It  is  similar 
to  Epsom  salt  in  its  action,  but  is  less  efficient,  more  apt  to  gripe,  and 
more  irritating.  It  ought  not  to  be  used  in  inflammatory  affections  of 
the  bowels. 

SODII  SULPHAS.  U.  S. — Sodium  Sulphate,  or  Glauber 's  Salt,  occurs 
in  six-sided,  very  efflorescent,  striated  prisms,  which  finally  crumble 
into  a  white  powder.  It  acts  like  Epsom  salt,  but  is  more  powerful  ;  it 
is,  however,  little  used  on  account  of  its  extremely  nauseous  taste.  It 
is  the  chief  active  principle  of  many  natural  purgative  waters  which  are 
so  useful  in  chronic  gastric  and  other  abdominal  catarrhs  with  consti- 
pation. The  combination  of  two  ounces  of  sodium  phosphate,  one-half 
ounce  of  sodium  sulphate,  and  one-half  drachm  of  potassium  iodide,  taken 
in  full  laxative  doses,  well  diluted,  upon  rising,  is  often  very  efficient  in 
such  cases  as  are  benefited  by  Carlsbad  waters.  Dose  of  sodium  sul- 
phate, one-quarter  to  one-half  ounce  (8-15  Gm. ). 

Soon  PHOSPHAS.  U.  S. — Sodium  Phosphate  occurs  in  colorless,  trans- 
parent crystals,  which  effloresce  and  become  opaque  on  exposure.  It  is 
a  tribasic  phosphate,  one  part  of  water  acting  as  a  base.  It  is  soluble 
in  5.8  parts  of  cold  water,  and  has  a  saline  taste,  closely  resembling  that 

cbrdant  that  it  does  not  seem  at  present  possible  to  come  to  any  conclusion.  The  drift  of 
the  evidence,  however,  seems  to  us  to  show  that  the  direct  action  upon  tissue-change  is 
very  slight,  and  that  it  is  incapable  of  producing  a  definite  and  fixed  result  amidst  the 
varying  and  complicated  daily  causes  which  inevitably  produce  more  or  less  disturbance 
and  variation  in  the  nitrogenous  elimination.  An  elaborate  research  upon  the  subject  has 
been  published  by  London  in  the  Zeilschr.f.  Klin.  Med.,  xiii.  i.  Most  of  the  literature 
of  the  subject  will  be  found  in  this  article,  the  original  work  of  which  seems  to  lead  to 
the  conclusion  just  stated. 


CATHARTICS.  669 

of  common  salt.  In  large  doses  it  is  a  mild  saline  purgative,  but  as  such 
is  not  at  present  very  much  employed.  Sodium  phosphate  is  a  very 
useful  remedy  in  chronic  infantile  diarrhoea  with  intestinal  indigestion, 
especially  as  it  occurs  in  bottle-fed  subjects.  It  appears  to  have  a  specific 
action  upon  the  liver  and  also  upon  the  intestinal  glands  in  general,  so 
that  it  is  often  of  great  service  where  there  are  habitually  chalky  stools 
or  white  fluid  motions,  and  in  many  cases  of  green  stools.  In  chronic 
hepatic  torpor  and  in  catarrhal  jaundice  it  is  often  used  with  great  advan- 
tage, and  it  seems  sometimes  of  value  in  litheemia. 

In  1888  Haig  affirmed,  as  the  result  of  his  experiments,  that  sodium  phosphate 
has  very  pronounced  effect  in  increasing  the  excretions  of  uric  acid.  In  a  subse- 
quent paper,  however,  he  stated  that  if  the  phosphate  contain  any  sulphate,  or  if  it 
be  in  the  form  of  the  acid  phosphate,  or  meet  with  an  acid  in  the  stomach  which 
should  make  it  an  acid  phosphate,  it  has  no  power  in  increasing  uric  acid  excretion; 
so  that  it  seems  to  us  that  at  present  we  cannot  consider  sodium  phosphate  as 
having  distinct  relations  with  uric  acid  excretion. 

Dose,  twenty  grains  to  half  an  ounce  (15  Gm. ) ;  laxative  for  infants, 
five  to  ten  grains.  Dose  of  SODII  PHOSPHAS  EFFERVESCENS,  U.  S. 
{Effervescent  Sodium  Phosphate},  twenty  per  cent,  phosphate,  two  drachms 
to  the  ounce  (8-32  Gm. ).  Dose  of  SODII  PHOSPHAS  EXSICCATUS, 
U.  S.  {Exsiccated  Sodium  Phosphas},  fifteen  grains  to  half  an  ounce. 

POTASSII  ET  SODII  TARTRAS.  U.  S. — Potassium  and  Sodium  Tar- 
trate, or  Rochelle  Salt,  is  made  by  the  addition  of  sodium  carbonate  to  a 
solution  of  potassium  bitartrate.  It  is  soluble  in  two  and  a  half  parts  of 
cold  water,  and  has  a  slightly  saline  taste.  It  is  a  mild  saline  purgative, 
dedidedly  less  efficient,  but  much  less  offensive  to  the  palate,  than  Epsom 
salt.  Dose,  from  half  an  ounce  to  two  ounces  (15-60  Gm. ). 

F.  Kleeberg*5  finds  that  the  intravenous  injection  of  potassium  sodium  tartrate 
(thirty  milligrammes  per  kilogramme)  produces  in  the  dog  a  marked  fall  of  the 
blood-pressure ;  after  toxic  doses,  slowing  of  the  heart  and  fatal  diastolic  arrest 
occur.  In  Kleeberg's  experiments  the  neutral  sodium  tartrate  (fifty  milligrammes 
per  kilogramme)  caused  a  rise  in  the  blood-pressure,  so  that  the  depressing  in- 
fluence of  the  double  salt  is  probably  due  to  the  potassium. 

PULVIS  EFFERVESCENS  COMPOSITUS.  U.  S. — Seidlitz  Powder  is  in 
two  packets;  the  white  paper  contains  about  thirty-five  grains  of  tartaric 
acid,  the  blue  paper  forty  grains  of  sodium  bicarbonate  and  two  drachms 
of  Rochelle  salt.  When  they  are  taken,  the  powders  are  dissolved  sepa- 
rately, the  solutions  added,  and  the  whole  drunk  while  effervescing. 
They  are  very  acceptable  to  the  stomach,  refrigerant  and  laxative  rather 
than  purgative.  Seidlitz  powders  are  used  almost  exclusively  to  evacuate 
the  bowels,  and  exhibited  after  blue  mass  to  "carry  off"  mercurials,  etc. 
They  should  be  taken  on  an  empty  stomach,  as  before  breakfast.  One 
powder  is  the  usual  dose;  but  not  rarely  even  two  powders  will  fail  to 
purge. 


670  LOCAL    REMEDIES. 

DRASTICS. 

As  already  stated,  the  drastics  are  those  vegetable  cathartics  which 
are  actively  irritant.  With  perhaps  one  or  two  exceptions,  in  sufficient 
amount  they  are  capable  of  causing  fatal  gastro-intestinal  irritation. 
The  line  between  the  drastics  and  the  stronger  purgatives  is,  of  course, 
placed  more  or  less  arbitrarily,  since  the  various  cathartics  differ  in 
action  almost  by  insensible  degrees.  Thus,  jalap,  although  included 
among  the  drastics  in  this  work,  might  with  perhaps  even  greater  pro- 
priety be  classed  among  the  purgatives,  since  it  is  very  little  more 
active  or  irritant  than  is  senna.  Further,  these  remedies  in  combina- 
tion seem  to  lose,  in  a  measure,  their  power  of  causing  irritation,  and 
to  become  useful  purgatives.  A  fact,  however,  which  makes  the  classi- 
fication here  employed  clinically  useful,  although  it  be  not  scientifically 
accurate,  is  that  none  of  these  remedies  should  be  used  when  a  purga- 
tive is  desired  to  relieve  gastro-intestinal  inflammation  or  irritation  ;  and, 
on  the  other  hand,  when  a  revulsive  action  is  wished  for,  as  in  some 
cases  of  brain  disease,  one  of  the  drastics  should  always  be  selected. 

JALAPA— JALAP.  U.  S. 

The  tuber  of  Ipomcea  Jalapa,  a  convolvulaceous  vine  growing  in 
Mexico.  Jalap  comes  into  the  market  in  two  forms  :  one,  that  of  the 
younger  roots,  which  are  sold  undivided  ;  the  other,  that  of  the  old 
roots,  which  are  brought  into  the  market  in  transverse  or  longitudinal 
slices  and  in  pieces.  The  first  variety  consists  of  very  hard,  irregularly 
globular,  brittle  roots,  about  the  size  of  a  shut  fist,  or  smaller,  and  often 
slashed  with  vertical  incisions,  made  for  the  purpose  of  facilitating 
drying.  The  active  principle  of  jalap  is  a  resin,  variously  known  as 
rhodeoretin  or  convolvulin,  closely  allied  to  the  resin  of  scammony. 

PHYSIOLOGICAL  ACTION. — Upon  dogs  and  horses  jalap  (Stilte46)  is 
said  to  act  as  a  powerful  hydragogue  cathartic,  and  in  overdoses  as  a  gas- 
tro-intestinal irritant.  Its  active  principles  are  absorbed,  since  Cadet  de 
Gassicourt  produced  diarrhoea  in  dogs  by  the  free  application  of  jalap  to 
the  shaven  skin,  and  J.  Muller47  found  the  resin  in  the  blood  of  dogs  to 
which  he  had  given  it.  Still6,  however,  asserts  that  it  does  not  impart  its 
purgative  properties  to  the  milk  of  nursing  women,  and  that  in  man  it 
is  not  absorbed  by  the  skin.  In  man  jalap  produces  free  hydragogue 
catharsis,  often  with  nausea  ;  or,  if  in  overdoses,  violent  vomiting  and 
purging. 

THERAPEUTICS. — Jalap  is  especially  indicated  when  it  is  desirable  to 
produce  large  watery  stools.  It  is,  however,  very  rarely  used  alone.  A 
favorite  combination  with  many  practitioners  is  of  it  and  calomel.  In 
the  form  of  the  compound  powder  (PULVIS  JALAP^E  COMPOSITUS,  U.  S. , 
— jalap,  thirty -five  parts,  cream  of  tartar,  sixty-five  parts),  jalap  is  very 
frequently  used  with  great  advantage  in  ascites  and  also  in  other  forms 


CATHARTICS.  671 

of  general  dropsy.  It  is  believed  when  given  in  this  way  to  exert  some 
influence  upon  the  renal  functions  :  for  very  many  cases  the  proportion  of 
cream  of  tartar  in  the  official  compound  powder  is  too  small. 

ADMINISTRATION. — The  dose  of  powdered  jalap  is  ten  to  twenty-five 
grains  (0.6-1.6  Gm. ) ;  of  the  extract,  ten  to  twenty  grains  (0.6—1.3  Gm. ). 
The  resin  (RESINA  JALAP^E,  U.  S. ),  like  the  other  purgative  resins,  is 
tasteless.  Dose  for  adult,  from  two  to  four  grains  (0.13-0.26  Gm. ). 

COLOCYNTHIS— COLOCYNTH.     U.  S. 

The  fruit,  deprived  of  its  rind,  of  Citrullus  Colocynthis,  or  bitter 
cucumber,  a  vine  growing  in  South  Africa,  Japan,  Syria,  Egypt,  Turkey, 
the  islands  of  the  Grecian  Archipelago,  etc.  The  fruit  is  a  round  gourd, 
from  two  to  four  inches  in  diameter,  of  a  whitish  or  pale  yellow  color.  It 
occurs  in  the  market  with  or  without  its  rind.  The  pulp  is  dry  and  mem- 
branous, whitish,  and  contains  the  active  purgative  glucoside  colocynthint 
first  discovered  by  Herberger. 

Colocynth  in  large  dose  is  an  irritant  hydragogue  cathartic,  capable  of 
destroying  life,  and,  according  to  Orfila  and  Schroff,  acting  upon  the  lower 
animals  as  upon  man.  Christison  records  the  death  of  a  woman  twenty- 
four  hours  after  taking  a  teaspoonful  and  a  half  of  the  powder.  Roques 
chronicles  a  fatal  result  produced  by  less  than  a  drachm  of  the  powder  in 
decoction,  but,  on  the  other  hand,  narrates  a  case  in  which  three  drachms 
failed  to  kill  (Husemann47),  and  W.  A.  Rolfe  reports  recovery  after  a 
quarter  of  an  ounce  of  the  powdered  drug  in  which,  although  pregnancy 
existed,  abortion  was  not  produced. 

ADMINISTRATION. — It  should  not  be  used  in  dropsy,  and  is  employed 
almost  solely  in  combination  with  other  purgatives.  The  full  purgative 
dose  of  the  extract  (EXTRACTUM  COLOCYNTHIDIS,  U.  S. )  is  three  to 
five  grains  (0.2-0.3  Gm. ).  The  compound  extract  (  EXTRACTUM  COLO- 
CYNTHIDIS COMPOSITUM,  U.  S. )  contains  extract  of  colocynth,  sixteen 
parts;  purified  aloes,  fifty  parts;  resin  of  scammony,  fourteen  parts;  carda- 
mom, six  parts;  soap,  fourteen  parts — as  laxative,  one  to  three  grains 
(0.06-0.2  Gm. );  as  purgative,  five  to  twenty  grains  (0.3-1.3  Gm.). 

SCAMMONIUM— SCAMMONY.     U.  S. 

A  resinous  exudation  from  the  root  of  Convolvulus  Scammonia,  a 
vine  growing  in  Syria.  It  is  said  to  be  obtained  by  cutting  off  the  root 
obliquely  about  two  inches  from  the  origin  of  the  stems,  and  catching  in 
shells  the  few  drachms  of  milky  juice  which  exude  from  each  root. 
From  these  shells  it  is  emptied  into  a  vessel  and  allowed  to  concrete. 
Formerly  scammonium  was  adulterated  to  a  great  extent  with  chalk, 
flour,  ashes,  sand,  etc.,  constituting  the  Factitious  Scammony  of  authors. 
Scammonin,  the  active  resin  of  scammony,  is  believed  to  be  identical 
with  jalapin,  originally  separated  by  Mayer  from  male  jalap,  and  closely 
allied  to  convolvulin  of  true  jalap.  The  Pharmacopoeia  requires  that 
scammony  shall  contain  seventy-five  per  cent,  of  this  resin.  Therapeu- 
tically  scammony  acts  like  jalap,  but  is  somewhat  more  irritating.  It 


672  LOCAL    REMEDIES. 

is  almost  solely  used  in  combination  with  other  cathartics,  and  on  ac- 
count of  its  frequent  adulteration  should  be  given  in  the  form  of  the 
resin  (RESINA  SCAMMONII,  U.  S. ).  Dose,  from  two  to  five  grains 
(0.13-0.3  Gm. ).  The  pure  or  Virgin  Scammony  is  in  irregular,  rough, 
fissured  masses,  of  various  sizes,  commonly  solid,  with  a  dull  resinous 
fracture,  and  of  a  dark  greenish  color,  inclining  to  black.  The  smell 
resembles  that  of  old  cheese. 

PILULE  CATHARTICVE  COMPOSITE.  U.  S.  —  Compound  Cathartic 
Pills  contain  each  approximately:  compound  extract  of  colocynth,  one 
and  one-third  grains;  extract  of  jalap,  one  grain;  calomel,  one  grain; 
gamboge,  one-fourth  grain.  In  the  dose  of  two  pills,  they  usually  produce 
large  watery  stools  without  much  pain,  and,  as  they  contain  mercury, 
have  some  cholagogue  influence.  The  mercury,  however,  makes  them 
as  an  habitual  laxative  much  inferior  to  the  vegetable  cathartic  pill 
(PILULE  CATHARTICS  VEGETABILES,  U.  S. ),  one  or  two  of  which  will 
usually  act  kindly  and  efficiently. 

PODOPHYLLUM— PODOPHYLLUM.  U.S. 

The  rhizome  of  Podophyllum  peltatum,  or  May-apple,  a  perennial 
herb,  growing  in  the  Northern  and  Middle  United  States.  Podophyllum 
occurs  in  simple  or  branched,  cylindrical,  brownish  pieces,  about  the 
thickness  of  a  goose-quill,  smooth  or  wrinkled  longitudinally,  often 
obscurely  marked  with  the  scars  of  leaf-scales,  and  furnished  with 
numerous  rootlets  or  their  remnants  attached  to  the  lower  surface.  The 
taste  is  bitterish,  acrid,  and  nauseous.  The  rhizome  contains  the  alkaloid 
berberine,  but  the  purgative  power  resides  chiefly  in  podophyllotoxin  * 
of  Podwyssotzki,49  although  it  is  probable  that  there  are  other  purgative 
substances  in  the  rhizome,  especially  an  uncrystallizable  resin,  podophyl- 
loresin. 

Podophyllum  is  a  rather  slowly  acting,  but  very  thorough  cathartic, 
whose  large  dose  either  in  man  or  in  most  of  the  domestic  animals  pro- 
duces violent  purging,  with  great  pain,  and  often  with  vomiting  ;  the 
symptoms  increasing,  if  the  dose  have  been  sufficient,  to  excessive  hyper- 
catharsis,  with  bloody  stools,  great  prostration,  and  death.  It  is  said  to 
act  when  given  hypodermically.  f  A  child  four  years  old  was  killed  by  an 
unknown  amount.  The  symptoms  were  repeated  vomiting,  slight  purging, 
collapse,  and  finally  coma,  ending  in  epileptiform  convulsions  (T.  G. 
Morton).  An  infant  twenty-two  months  did  recovered  from  four  grains.49 

*  Podophyllotoxin  was  believed  by  its  discoverer  to  be  composed  of  picropodophyllin 
in  combination  with  podophyllinic  acid.  The  latest  chemical  researches  indicate,  how- 
ever, that  these  substances  are  decomposition  products.  Podophyllotoxin  appears  to  be 
a  very  irritant,  active  cathartic,  and  has  been  used  in  medicine  in  doses  of  one-fifteenth 
of  a  grain.  According  to  J.  Neuberger  (Arch.f.  Exper.  Path.  u.  Pharm.,  1890,  xxviii.), 
it  causes  in  the  lower  animals  violent  purging  and  severe  nephritis,  with  fall  of  the  arte- 
rial pressure  and  death  from  exhaustion. 

t  See  Amer.  Med.  Times,  iv. ;  also  Med.  Times  and  Gaz.,  March.  1863. 


CATHARTICS.  673 

In  therapeutic  doses  it  is  believed  by  very  many  practitioners  to  act 
especially  upon  the  liver,  and  is  much  used  in  acute  constipation  and  in 
so-called  bilious  attacks.  As  ten  or  more  hours  are  usually  required  for 
its  action,  it  should  not  be  combined  with  quick  cathartics.  With  calo- 
mel it  acts  very  well.  The  only  preparation  that  should  be  used  is  the 
resin  (RESINA  PODOPHYLLI,  U.  S. ),  or  podophyllin,  the  laxative  dose  of 
which  is  one-twelfth  to  one-sixth  grain  (0.005-0.01  Gm. ),  the  purgative 
dose,  one-sixth  to  one-half  grain  (0.01-0.03  Gm. ).  It  is  very  advanta- 
geously combined  with  extract  of  belladonna  as  in  the  PILULE  PODO- 
PHYLLI BELLADONNA  ET  CAPSICI,  U.  S.  (Pills  of  Podophylhim,  Bella- 
donna, and  Capsicum),  each  of  which  contains  about  one-quarter  grain  of 
the  resin  of  podophyllum.  The  fluid  extract  (FLUIDEXTRACTUM  PODO- 
PHYLLI, U.  S. )  is  an  inelegant  preparation;  dose,  eight  minims  (0.5 
Cc.). 

ELATERIUM. 

A  substance  deposited  by  the  juice  of  the  fruit  of  Ecballium  ela- 
terium,  or  squirting  cucumber,  a  native  of  Greece,  but  cultivated  in 
England.  In  the  interior  of  the  ovate  fruit  is  an  elastic  sac,  which  con- 
tains the  seeds,  and  at  ripening  becomes  so  distended  with  juice  that 
when  the  fruit  falls  off  the  vine,  and  the  support  is  removed  from  the 
stem  end,  a  rupture  occurs  at  the  latter  position,  and  the  liquid  with  the 
seeds  is  forcibly  projected.  The  medicinal  principle  is  said  to  be  con- 
tained only  in  this  inner  juice.  In  order  to  avoid  loss,  the  fruit  is  picked 
with  a  piece  of  the  stalk  adherent  to  it  before  ripening,  and  is  opened  by 
slicing.  Elaterium  occurs  in  light,  friable,  slightly  incurved,  greenish- 
gray  cakes  about  a  line  thick.  The  taste  is  acrid  and  bitter,  the  fracture 
finely  granular.  Owing  to  the  variability  of  commercial  elaterium,  the 
U.  S.  Pharmacopoeia  now  recognizes  only  the  active  principle,  Elaterin 
(ELATERINUM,  U.  S. ),  which  was  first  separated  in  a  pure  state  by  Mor- 
ries.51  It  crystallizes  in  colorless,  shining,  rhombic,  six-sided,  odorless 
tables,  of  a  very  bitter  sharp  taste  and  neutral  reaction. 

PHYSIOLOGICAL  ACTION. — Locally  applied,  elaterium  is  a  very  de- 
cided irritant,  producing,  according  to  Pereira,  ulcerations  in  the  fingers 
of  those  who  handle  the  fruit  and  prepare  the  drug  for  market.  When 
taken  internally,  it  acts  on  man  as  a  most  powerful  hydragogue  cathartic. 

On  the  lower  animals  its  action  is  much  less  certain.  Viborg  asserts  that  a 
horse  was  unaffected  by  a  pound  of  elaterium  fruit ;  and  H.  C.  Wood  has  given  one 
and  even  two  grains  of  a  presumably  active  elaterium  to  a  dog  without  producing  very 
obvious  results.  If  the  dose  be  sufficiently  large,  all  animals  probably  are,  however, 
fatally  affected  by  elaterium,  perishing  by  progressive  depression.  Stille" M  asserts 
that  the  death  is  not  rarely  preceded  by  violent  vomiting  and  purging  ;  and  even 
when  these  are  absent  during  life,  post-mortem  examination  reveals  congestion  and 
inflammation  of  the  gastric  and  intestinal  mucous  membranes.  In  none  of  our 
own  experiments,  which  have  not  been  numerous,  has  any  purging  been  present ; 
further,  in  K6hler*sM  elaborate  investigation,  elaterium  dissolved  in  alcohol  was  in- 
jected under  the  skin,  the  powdered  elaterium  was  put  into  the  rectum,  and  was 
given  by  the  mouth  after  the  gall-duct  had  been  tied  so  as  to  prevent  the  flow  of 

43 


674  LOCAL   REMEDIES. 

bile  into  the  intestine,  and  in  neither  case  was  there  any  purging,  but  prostration, 
apathy,  disturbed  respiration,  salivation,  and  violent  convulsions,  ending  in  death. 
From  these  experiments  Kohler  draws  the  conclusion  that  elaterium  exerts  a  general 
action  upon  the  system,  for  which  its  introduction  into  the  blood  is  all  that  is  requi- 
site, and  also  a  purgative  influence,  for  which  it  is  necessary  that  there  be  bile  in 
the  duodenum  to  dissolve  the  elaterium  and  cause  it  to  act  locally  on  the  intestine. 
The  objection  to  this  conclusion  is  that  it  seems  probable  that  elaterium  does  not 
purge  dogs  and  rabbits,  even  when  given  by  the  mouth.  Further,  elaterium  applied 
externally  will  cause  purging  in  man  (Stille').  So  that  the  application  to  man  of 
the  conclusions  arrived  at  by  Kohler  is  incorrect.  Kohler' s  experiments  proved 
that  in  animals  elaterium  is  absorbed,  even  when  given  by  the  mouth,  since  he 
found  it  in  the  urine  of  poisoned  dogs  and  rabbits. 

THERAPEUTICS. — Elaterium  is  certainly  the  most  efficient  of  all  the 
hydragogue  cathartics,  producing  in  properly  regulated  doses  the  freest 
evacuations  with  comparatively  little  pain  and  irritation.  It  is  the  most 
efficient  of  all  the  medicines  of  the  class  in  general  dropsy  or  in  ascites. 
As,  however,  its  action  is  very  exhausting,  great  care  should  be  exercised 
not  to  give  it  in  too  large  doses,  and  also  to  support  the  strength  of  the 
patient  during  the  period  of  purgation,  and  afterwards,  by  alcoholic 
stimulants,  easily  digested  nutritious  food,  and  appropriate  hygienic 
measures.  In  the  latter  stages  of  dropsy  the  injudicious  use  of  elaterium 
may  cause  a  fatal  exhaustion.  For  the  asserted  power  of  elaterium  in 
increasing  the  intestinal  elimination  of  urea  we  have  been  unable  to  find 
authority.  Clinical  experience  has,  however,  demonstrated  the  value  of 
elaterium  in  tir&mia.  In  order  to  deplete,  elaterium  has  been  employed 
in  various  diseases  ;  but  this  use  is  not  to  be  encouraged,  and  especially 
when  there  is  any  gastro- intestinal  irritation  or  inflammation  are  the 
salines  much  preferable  to  elaterium. 

Elaterium  is  without  doubt  capable  of  destroying  life,  but  we  know  of 
but  one  recorded  death, — that  of  a  woman  in  whom  two  and  two-fifths 
grains  of  the  extract  of  elaterium  and  sixteen  grains  of  rhubarb  caused 
uncontrollable  vomiting  and  purging,  ending  in  a  fatal  gastro-enteritis.* 

Dose,  one-sixth  of  a  grain  (o.oi  Gm. ),  combined  with  extract  of 
hyoscyamus  or  of  belladonna  and  an  aromatic  oil.  Dose  of  the  official 
elaterin,  one-twentieth  of  a  grain  (0.003  Gm. )  ;  of  the  trituration  (TRIT- 
URATIO  ELATERINI — ten  per  cent.,  U.  S. ),  half  a  grain  (0.03  Gm. ). 
Elaterium  when  injected  hypodermically  purges  freely,  but  also  produces 
an  excessively  severe  local  irritation,  even  fatal  tetanus. f 

CAMBOGIA— GAMBOGE.     U.S. 

A  gum  resin,  obtained  in  Siam  by  breaking  off  the  leaves  and  young 
shoots  of  the  tree  known  by  botanists  as  Garcinia  hanburii  and  catching 
in  suitable  vessels  the  juice  as  it  drops.  When  the  receptacles  consist 
of  hollow  bamboos,  the  juice  hardens  into  cylindrical  casts,  striated  ex- 
ternally, and  with  a  central  cavity  due  to  the  loss  of  substance  in  drying. 

*  See  Beck's  Medical  Jurisprudence,  I2th  ed.,  ii.  719. 
t  See  Therap.  Gaz.,  ii.  27. 


CATHARTICS.  675 

This  is  the  so-called  pipe  gamboge.  Gamboge  in  sorts  occurs  in  irregular 
masses.  Gamboge  is  a  hard,  resinoid  substance,  of  a  brittle,  often  con- 
choidal  fracture,  of  a  deep  reddish-orange  color  on  exposed  surfaces, 
more  yellowish  when  freshly  broken,  affording  a  bright  yellow  powder, 
insoluble  in  water,  with  which  it  forms,  however,  an  intensely  yellow 
emulsion.  It  has  little  or  no  taste,  but  when  chewed  produces,  after  a 
time,  an  acrid  sensation  in  the  fauces. 

PHYSIOLOGICAL  ACTION. — Gamboge  acts  upon  man  as  a  violently 
irritant  cathartic.  On  the  lower  animals  it  has  a  similar  influence,  but 
Schaur  and  Orfila  state  that  when  in  large  dose  it  often  fails  to  purge, 
producing  rapidly  fatal  gastro-enteritis,  so  intense  as  seemingly  to  par- 
alyze the  bowels.  According  to  Daraszkiewicz  M  and  to  Schaur,  in  order 
for  gambogic  acid  to  act  as  a  purgative  the  presence  of  bile  in  the  intes- 
tine is  necessary.  Schaur  and  Richter  affirm  that  gamboge  upon  raw 
surfaces  acts  simply  as  an  irritant  :  further,  Gmelin  and  Tiedemann  assert 
that  they  have  found  its  principles  in  the  urine  ;  it  may  therefore  well  be 
that  solution  by  the  alkaline  fluids  of  the  intestines  is  necessary  for  its 
purgative  action.  Lewis,  Abeille,  and  Ferriar  state  that,  when  given  in 
certain  ways,  gamboge  acts  as  a  decided  diuretic.  If  this  be  true,  ab- 
sorption of  its  active  principle  must  occur.  Schaur  was  not  able,  how- 
ever, to  detect  it  in  the  urine  of  persons  or  of  animals  taking  it.  Even 
when  he  injected  large  quantities  of  it  into  the  blood  of  dogs  he  failed  to 
find  it  in  the  urine,  although  he  did  obtain  a  resinoid  substance  which  he 
believes  to  be  a  derivative. 

Gamboge  is  so  irritant  that  it  is  used  in  practical  medicine  only  to 
give  sharpness  to  purgative  combinations.  The  full  purgative  dose 
would  be  from  two  to  five  grains  (o.  13-0.3  Gm. ). 

OLEUM    TIGLII— CROTON    OIL.     U.S. 

The  fixed  oil  obtained  from  the  seeds  of  Croton  Tiglium,  a  euphor- 
biaceous  shrub  of  Hindostan  and  other  portions  of  Southern  Asia.  This 
oil  is  quite  viscid,  varies  in  color  from  a  pale  yellow  to  a  dark  reddish 
brown,  and  has  an  acid  reaction.  Its  taste  is  hot,  acrid,  and  extremely 
persistent  ;  its  odor  faint,  but  peculiar.  Croton  oil  consists  chiefly  of 
the  glycerites  of  ordinary  fatty  acids,  but  contains  also  crotonoleic  acid* 
which  has  been  supposed  to  be  its  pure  active  principle,  but  is  stated  by 
Dunstan  and  Boole  to  be  a  mixture  of  inactive  oily  acids  with  a  power- 
fully vesicating,  resinous  substance,  croton-resin. 

THERAPEUTICS. — Locally  applied,  croton  oil  is  an  intense  irritant, 
producing  upon  the  skin  an  eruption  which  is  at  first  papular  but  in  a 
very  short  time  becomes  pustular.*  (See  COUNTER-IRRITANTS.)  Ad- 
ministered internally,  croton  oil  produces  in  man  and  in  most  of  the  lower 
animals  violent  purging,  with  severe  griping,  and  is  capable  of  causing  a 
fatal  gastro-enteritis.  Its  action  on  the  intestine  is  probably  in  part  local 

*  For  a  histological  study  of  the  eruption,  see  Wiener  Med.  Wochenschr.,  1897,  xlviL 
1021. 


676  LOCAL   REMEDIES. 

and  in  part  through  absorption.  In  the  experiments  of  Hertwig  (quoted 
by  Still6)  and  of  Buchheim,"  purgation  did  not  follow  the  injection  of  the 
oil  into  the  veins  of  animals;  but  Conwell  obtained  a  result  contrary  to 
this,  and  there  is  considerable  testimony  that  its  external  use  in  man  is 
sometimes  followed  by  purging  (Still6),  and  even  by  fatal  results.*  The 
experiments  of  Robert  and  of  Hirschheydt x  seem  to  prove  that  crotonoleic 
acid  is  both  the  purgative  and  vesicant  active  principle  :  it  exists  in  the 
oil  combined  with  glycerin.  It  is  believed  that  the  glycerite  is  slowly 
decomposed  in  the  intestines,  and  that  the  acid  which  is  thus  set  free 
acts  progressively.  Certainly,  Hirschheydt  found  that  pure  crotonoleic 
acid,  which  has  appeared  in  commerce,  is  not  a  practical  purgative,  ten 
milligrammes  being  very  uncertain  in  their  effects,  whilst  large  doses  are 
prone  to  produce  excessive  gastro- intestinal  irritation.  Injected  into  the 
blood,  crotonoleic  acid  was  found  to  be  an  exceedingly  active  depressant 
to  the  circulation.  The  amount  of  free  crotonoleic  acid  in  croton  oil 
increases  very  markedly  with  age.  On  this  account  old  croton  oil,  with 
an  acid  reaction,  acts  much  more  harshly  than  does  the  recent  neutral  or 
nearly  neutral  oil,  and  should  be  rejected  for  internal  use. 

Croton  oil  is  chiefly  used  in  practical  medicine  in  mania,  apoplexy,  or 
other  diseases  in  which  there  is  difficulty  in  administering  a  cathartic.  It 
is  also  given  in  cases  of  very  obstinate  constipation  when  less  active  reme- 
dies have  failed.  It  is  the  one  cathartic  employed  when,  as  in  some 
brain  diseases,  it  is  desired  to  revulse  by  the  intestines.  The  dose  is  one 
drop,  in  emulsion,  or  by  simply  placing  it  upon  the  tongue.  In  over- 
doses, croton  oil  is  a  violent  poison. 

TOXICOLOGY. — Although  in  small  amounts  croton  oil  causes  such 
severe  symptoms,  yet  in  larger  quantities  it  has  failed  to  produce  as 
serious  results  as  would  be  naturally  expected.  It  is,  however,  very 
possible  that  in  at  least  some  of  the  recorded  cases  the  oil  was  adul- 
terated. Cowan  has  reported  a  case  (Husemann57)  of  a  child  four  years 
old  who  recovered  in  two  days  from  a  teaspoonful  of  croton  oil  taken  on 
a  full  stomach  ;  Adams  (Husemann)  saw  recovery  in  an  adult  after  the 
ingestion  of  a  drachm  ;  and  the  case  is  recorded  of  a  woman  M  who  took 
about  an  ounce,  was  vomited  forty-five  minutes  afterwards  with  mustard, 
and  finally  recovered.  The  minimum  fatal  dose  is  not  known,  and  prob- 
ably varies  greatly.  A  child59  aged  thirteen  months  was  killed  by  a 
quantity  believed  not  to  exceed  three  minims.  Giacomini  (Still6)  reports 
a  case  in  which  twenty-four  grains  of  the  drug  proved  fatal  in  as  many 
hours  :  although  there  were  but  four  stools,  the  patient  presented  the 
symptoms  of  general  collapse,  preserving  consciousness  to  the  last.  A 
little  less  than  two  drachms  has  caused  vomiting  and  death  without 
purging.59! 


*  See  Schmidt's  Jahrb.,  clxiv. ;  also  Robert's  Arbeiten,  1890,  iv.  45. 
t  For  other  cases,  see  Med.  Gaz.,  xliii. ;  Edinb.  Med.  Journ.,  1861 ;  Lancet,  1870,  i.  ; 
Brit.  Med.  Journ.,  1874,  i. ;  Ann.  d'Hyg.,  1871,  i. ;  also  Robert's  Arbeiten,  1890,  iv. 


CATHARTICS. 


677 


The  treatment  of  croton-oil  poisoning  is  purely  symptomatic.  Opium 
should  be  given  to  lessen  the  purging,  demulcent  drinks  to  lessen  the  irri- 
tation. If  collapse  develops,  cardiac  stimulants  should  be  administered 
hypodermically  and  bodily  temperature  maintained  by  the  application  of 
external  heat. 


REFERENCES. 


CATHARTICS.  32. 

1.  THIRY Sb.  G.  W.,  1.  33. 

2.  RADZIEJEWSKI  .   .  V.  A.  P.  A.,  1870,  37.  34. 

3.  ASP Ludwig's  Arbeiten,  1868.  35. 

4.  SCHIFF Nuove        Richerche       sul  36. 

Potere   Digerente,    Mor-  37. 

.     gagni,  1867.  38. 

5.  MOREAU A.  G.  M.,  6  s.,  xvi.  234.  39. 

6.  THIRY Gaz.  Med.,  1871.  40. 

7.  BRUNTON    ....  Med.  Press  and  Circular, 

Dec.  31,  1873.  41. 

8.  BRUNTON    ....  Pract.,  May,  1875.  42- 

9.  VULPIAN Gaz.  M£d.,  1873,  300.  43. 

10.  LEGROS Gaz.  M6d.,  1873.  44. 

11.  HOUCKGEEST      .     .  A.  G.  P.,  1872,  266.  45. 

12.  HAY J.  A.  P.,  xvi. ;  xvii.  46. 

13.  CLOPATT     .  .  .  .  S.  Jb.,  1896,  ccli.  47. 

14.  HEADLAND     .  .   .  Action  of  Medicines,  Lon-  48. 

don,  1867,  443. 

15.  ROHRIG Strieker's  Med.  Jahrbuch.,  49. 

1873.  5°- 

16.  RUTHKRFORD    .   .  Tr.  R.  S.  Ed.,  xxix. 

17.  HEINRICHSEN  .  .  S.  Jb.,  ccii.  214.  51. 

18.  ROHRIG Exper.    Untersuch.    u.    d. 

Physiol.     der     Gallenab-  52. 

sond.,  Vienna,  1873.  53. 

19.  FRONMULLER    .  .  Med.-Chir.  Centralb.,  1879,  54. 

xiv. 

20.  KOHN S.  Jb.,  cxciv.  246.  55. 

21..  MILLER Z.  K.  M.,  1881,  iv.  56. 

22.  KOHLSTOCK   .   .   .  Charite     Annalen,      1892,  57. 

xvii.  58. 

23.  GILBERT  and  DOMINICI  .  C.  R.  S.  B.,  1895,  ii.  59. 

24.  PATON B.  M.  J.,  1886,  i.  60. 

25.  REGENSBURGER  .  C.  M.  W.,  1877,  328.  61. 

26.  DOIT     Gaz.    des    Hop.,  Oct.    24, 

1885.  62. 

27.  WOROSCHILSKY     .  T.  M.,  XV'i.  63. 

28.  BUCHHEIM  .    .    .   .  V.  A.  P.  A.,  xii.  64. 

29.  SIMON Animal  Chemistry,  Syden-  65. 

ham  Soc.  Trans,  ii.  386.  66. 

30.  BIRD London   Med.   Gaz.,  1845,  67. 

Soi.  68. 

31.  MICHEA L.  L.,  1849,  i.  15.  69. 


WASSILIEFF  .   .  .  Z.  P.  C.,  1882. 
SMITH,  T.  and  H.  .  Chem.  Gaz.,  1851. 

GROVES Pharm.  Journ.,  xvi. 

MEYER A.  E.  P.  P.,  1890,  xxviii. 

KOHN S.  Jb.,  cxciv.  246. 

BRANDENBURG  .   .  In.  Dis.,  Berlin,  1893. 
DIETRICH  ....  In.  Dis.,  Dorpat,  1885. 

BARKER Amer.  Pract.,  1872. 

DRAGENDORFF   and    KUBLY  .  Vierteljahr.   f 

Prakt.  Pharm.,  xvi. 
STOCKMAN  .   .   .   .  A.  E.  P.  P.,  xix.  120. 

RECKE In.  Dis.,  Gottingen,  1881. 

SANG L.  L.,  1891,  ii. 

CURCI L.  M.  R.,  Oct.  1886. 

LUTON G.  H.  M.  C.,  1874,  455. 

STILLE     Therapeutics,  ii. 

MULLER In.  Dis.,  Dorpat,  1885. 

HUSEMANN     .   .   .  Handbuch    der    Toxicolo- 

gie, 625. 
PODWYSSOTZKI     .  A.  E.  P.  P.,  xiii.  40. 

Australasian  Med.  Gaz.,  ii. 

237- 
MORRIES     ....  Reper.  f.   Pharm.,   xxxix. 

134- 

STILL£ Therapeutics,  ii.  459. 

KOHLER V.  A.  P.  A.,  1.  287. 

DARASZKIEWICZ  .  Meletemata  de  Resinarum, 

Dorpat,  1858. 

BUCHHEIM  .  .  .  .  V.  A.  P.  A.,  xii.  i. 
HIRSCHHEYDT  .   .  Robert's  Arbeiten,  1890,  iv. 
HUSEMANN    .  .   .  Toxicologie,  ii.  443. 

B.  M.  S.  J.,  1868,  i.  294. 
M.  T.  G.,  1870,  i. 
A.  J.  M.  S.,  April,  1874. 
MACCALLUM  .   .   .  University   of    California, 

vol.  i. 

DIXON B.  M.,  1902,  ii. 

RAVIART S.  M.,i895- 

TOY S.  M.,  1900. 

HEINZE P.  N.  W.,  1903. 

KI.EEBERG  ....  Amer.  Med.,  1903,  vi. 
STADELMANN    .   .  B.  K.  W.,  xxxiii. 

BAIN B.  M.J.,  1898,1. 

PFAFF  and  BALCH  .  J.  Ex.  M.,  ii. 


FAMILY   IV.— DIURETICS. 


DIURETICS  are  medicines  used  for  the  purpose  of  increasing  the  flow 
of  urine.  Some  of  them  act  directly  upon  the  secreting  structure,  but 
others  only  in  some  indirect  way,  as  by  increasing  the  blood  supply  to 
the  kidney.  It  is  notorious  that  diuretics  often  fail  in  practice  when 
their  action  is  most  urgently  needed.  This  result  arises,  in  many  cases, 
from  the  nature  of  the  disease,  and  is  not  because  diuretics  are  powerless 
or  uncertain.  Thus,  in  cardiac  disease  the  congestion  of  the  kidneys  may 
be  so  great  as  to  render  secretion  impossible  ;  and  it  is  equally  evident 
that  when  the  secretory  cells  have  been  destroyed,  as  in  advanced  Bright' s 
disease,  diuretics  must  be  powerless. 

There  are  certain  agencies  whose  influence  upon  the  kidneys  should 
never  be  lost  sight  of  in  exhibiting  diuretics.  Thus,  cold,  by  checking 
the  secretion  of  the  skin,  often  acts  as  a  most  efficient  remedy  of  the 
class.  Again,  mere  vascular  fulness  tends  to  provoke  excretion  of  water 
by  the  kidneys.  E.  Roux l  found  that  the  ingestion  of  large  quantities  of 
water  greatly  increased  the  flow  of  urine,  but  did  not  sensibly  affect  the 
elimination  of  urea  or  uric  acid,  although  the  elimination  of  the  chlorides 
seemed  to  be  augmented  ;  in  Bocker'  s 2  experiments,  however,  large 
draughts  of  water  increased  not  only  the  amount  but  also  the  solids  of 
the  urine.  The  investigations  of  J.  Meyer3  explain  these  discrepancies 
and  show  how  water  may  be  of  service  in  various  diseases.  Meyer  found 
that  when  the  tissues  were  full  of  the  products  of  disintegration,  the 
effect  of  water  in  increasing  elimination  was  very  marked,  but  that  upon 
the  wasting  processes  of  the  body  the  water  exerted  no  influence.  It 
would  seem,  therefore,  that  while  we  cannot  by  water  produce  tissue- 
disintegration,  we  can  by  it  wash  out  the  retained  products  of  tissue- 
change  ;  and  the  great  rarity  of  uninherited  gout  in  America  probably 
has  some  connection  with  the  universal  habit  of  drinking  water  very 
freely.  Large  draughts  of  simple  water  at  regular  intervals  often  act  very 
favorably  in  acute  Bright1  s  disease,  greatly  increasing  the  urinary  flow 
and  at  the  same  time  lessening  the  irritation  of  the  kidneys.  The  origi- 
nal assertion  of  Porak  and  Bernheim,4  that  in  violent  irritation  of  the 
kidneys,  in  suppression  of  urine,  in  grave  acute  Bright' s  disease,  and  in 
similar  conditions  great  good  could  often  be  achieved  by  hypodermoclysis, 
is  abundantly  confirmed.  This  procedure  consists  in  the  injection  deep 
into  the  cellular  tissue  of  the  buttocks  of  a  thoroughly  and  very  recently 
678 


DIURETICS.  679 

sterilized  normal  salt  solution  ;  *  a  half-pint  to  a  pint  of  the  liquid,  at  a 
temperature  of  about  100°  F.,  may  be  slowly  introduced  without  causing 
local  irritation  or  giving  much  pain.  A  fountain  syringe  placed  about 
three  feet  above  the  patient  affords  sufficient  power  to  slowly  force  the 
liquid  through  a  large  hollow  needle.  In  various  inflammations  or  irrita- 
tions of  the  genito-urinary  organs,  as  in  gravel,  whenever  it  is  desired  to 
make  the  secretion  less  irritating  or  less  concentrated,  the  value  of  water 
as  an  adjuvant  to  medicinal  diuretics  should  always  be  taken  advan- 
tage of. 

That  under  various  circumstances  washing  out  of  the  blood,  or,  as  Pierre 
Delbert 5  calls  it,  lavage  of  the  blood,  may  be  useful  is  shown  by  his  experiments, 
in  which  it  was  found  that  the  free  intravenous  injection  of  saline  solution  com- 
menced immediately  after  the  hypodermic  injection  of  a  fatal  dose  of  strychnine  in 
the  dog  was  able  to  prevent  the  development  of  the  strychnine-poisoning,  the  excess 
of  water  in  the  blood  evidently  causing  elimination  to  almost  keep  pace  with  ab- 
sorption. 

There  is  a  very  marked  antagonism  between  the  bowels,  the  skin, 
and  the  kidneys,  so  that  great  activity  in  the  function  of  one  of  these 
emunctories  lessens  secretion  in  the  others.  When  a  diuretic  action  is 
desired,  sweating  and  purging  should  be  avoided.  When  a  diuretic  is 
exhibited,  the  patient  should  be  kept  cool,  walking  about,  if  able,  or  if 
it  is  necessary  for  him  to  remain  in  bed  he  should  be  covered  lightly. 
Not  rarely,  a  remedy  which  when  administered  cold  and  the  patient  kept 
cool  afterwards  will  act  as  a  diuretic,  will  when  it  is  given  hot  and  the 
patient  kept  warm  act  as  a  diaphoretic. 

The  chief  indications  for  the  use  of  diuretics  are  as  follows  : 

1.  To  maintain  the  action  of  the  kidneys.     It  is  hardly  necessary  here 
to  discuss  the  necessity  of  excretion  to  the  system.      In  various  kidney 
diseases  this  indication  is  very  urgent ;    but  as  the  lessened  excretion 
too  often    depends    upon  a  profound  organic    alteration   of   the   renal 
secreting    structure,   it    is  evident   that  very  frequently  diuretics    must 
fail  when  most  needed.      In  the  great  majority  of  cases  in  which  diu- 
retics are  used  to  fulfil  the  present  indication,  only  the  mildest  of  the 
class   should   be  employed.     Whenever   there   is   inflammation   of   the 
kidneys,  even  if  it  be  chronic,  irritating  diuretics  should   be   avoided. 
When   lessened  urinary    excretion   is   purely   functional    in   its    origin, 
diuretics  are  often  most  serviceable.     In  fevers   especially  is  it  neces- 
sary to  maintain  the  action  of  the  kidneys  ;  for  this  purpose  water  should 
always  be  freely  given  during  fever.     The  alkaline  diuretics  sometimes 
may  be  exhibited  ;  but  the  most  generally  serviceable  of  all  remedies  of 
the  class  in  the  febrile  state  is  the  sweet  spirit  of  nitre. 

2.  To  evacuate  fluid.     For  this  purpose  hydragogue  diuretics  are 
employed  in  all  forms  of  dropsy. 

*  Normal  salt  solution  is  a  0.7  per  cent,  solution  of  common  salt  in  distilled  or  pure 
water.  For  practical  purposes  it  can  be  made  by  dissolving  a  teaspoonful  of  salt  in  a 
pint  of  water. 


680  LOCAL    REMEDIES. 

3.  To  soothe  and  diminish  irritation   of  the  genito-urinary  organs. 
The  value  of  water  in  fulfilling  this  and  the  next  indication  has  already 
been  pointed  out.      By  lessening  the  acidity  of  the  urine  and  rendering 
soluble  the  uric  acid  which  is  present,  the  alkalies  are  equally  important 
in  carrying  out  the  present  and  the  following  indication. 

4.  To  alter  the  urinary  secretion  so  as  to  prevent  the  deposition  of 
calculons  material.      Notwithstanding  it  has  been  otherwise  asserted,  no 
practical  measure  has  as  yet  been  devised  of  dissolving  a  calculus  when 
once  formed.      Even  to  alter  the  urine  so  as  to  prevent  further  deposition 
is  probably  impracticable,  except  in   cases  of   uric  acid  or   phosphatic 
diathesis. 

Diuretics  are  very  naturally  divisible  into  two  sets, — the  hydragogue 
diuretics  and  the  depurant  diuretics.  These  classes,  of  course,  grade  more 
or  less  into  each  other,  but  they  are  sufficiently  distinct  for  practical 
purposes.  The  drugs  belonging  to  the  first  set  simply  increase  the  flow 
of  water  from  the  kidneys,  and  are  therefore  used  chiefly  for  the  relief  of 
dropsy  ;  those  of  the  second  division  exert  a  marked  sedative  action 
upon  the  system,  and  generally  do  not  increase  to  any  great  extent  the 
water  of  the  urine,  but  modify  the  secretion  in  one  way  or  another,  and 
are  mostly  given  to  render  the  urine  less  irritant  or  for  their  sedative  and 
eliminative  action  in  acute  disease. 

Under  the  heading  of  stimulant  diuretics  are  considered  certain  sub- 
stances which  do  not  of  necessity  increase  the  flow  of  urine,  but  whose 
active  principles  are  eliminated  by  the  kidneys,  and  by  actual  contact 
affect  the  mucous  membrane  of  the  genito-urinary  organs. 

HYDRAGOGUE   DIURETICS. 

SCILLA— SQUILL.     U.  S. 

The  bulb  of  Urginea  maritima,  a  liliaceous  plant  growing  in  the  south 
of  Europe,  especially  on  the  shores  of  the  Mediterranean.  The  bulb 
varies  in  size  from  that  of  a  child's  head  to  that  of  the  fist.  It  is  com- 
posed of  numerous  layers  or  scales,  which  separate  when  it  is  sliced  for 
drying.  As  kept  in  the  shops,  squill  is  in  horny  flakes,  of  a  white  or 
red  color,  becoming  leathery  when  wet,  and  having  an  acrid  bitter  taste. 
It  yields  to  water  and  alcohol  and  also  to  vinegar. 

The  nature  of  the  active  principle  of  squill  has  not  been  established. 
A  number  of  glucosides  have  been  described  by  chemists,  and  Merck  has 
put  upon  the  market  three  substances,  scillin,  scillipicrin,  and  scillitoxin* 
There  is,  however,  no  sufficient  proof  as  to  which,  if  any,  of  these  sub- 

*  Fronmiiller  has  reported  (Memorabilien,  1879,  xxiv.  250)  a  series  of  experiments 
made,  upon  persons  suffering  from  various  ailments,  with  the  scillin,  scillipicrin,  and 
scillitoxin  of  Merck.  He  found  that  scillitoxin  in  doses  of  0.45  grain  acted  as  a  rather 
uncertain  diuretic,  and  frequently  caused  giddiness,  headache,  and  loss  of  appetite ; 
scillin  seemed  to  be  devoid  of  diuretic  properties ;  while  a  gramme  of  a  solution  of  scilli- 
picrin in  water  (one  part  in  fifty)  administered  hypodermically  usually  caused  a  great 
flow  of  urine,  without  other  evil  symptoms  than  some  smarting  at  the  place  of  injection. 


DIURETICS.  681 

stances  represents  the  crude  drug.      Scillitin  of  the  older  writers  and  of 
Merck  was  a  complex  body. 

PHYSIOLOGICAL  ACTION. — In  small  doses  squill  acts  upon  man  as  a 
stimulating,  slightly  irritating,  diuretic.  In  large  doses  it  causes  great 
abdominal  pain,  violent  purging  and  vomiting,  lessened  or  almost  sup- 
pressed secretion  of  bloody  albuminous  urine,  with  slow  pulse,  ending,  it 
may  be,  in  collapse,  convulsions,  and  death. 

Upon  the  lower  animals  squill  acts  very  much  as  it  does  upon  man,  producing 
vomiting,  violent  purging,  muscular  weakness,  dulness,  stupor,  disturbed  respira- 
tion, muscular  weakness  deepening  into  paralysis,  tremors  disappearing  in  convul- 
sions, and  finally  death  in  the  course  of  twelve  or  fifteen  hours  if  the  dose  have 
been  sufficient.  In  the  experiments  of  Schroff6  upon  rabbits,  scillitin  of  Merck 
differed  from  the  alcoholic  extract  of  squill  in  its  effect  upon  the  pulse  and  upon  the 
pupil,  and  in  the  post-mortem  appearances  produced  by  it,  the  pericardial,  sub- 
pleural,  and  pulmonary  hemorrhages,  and  the  gastric  erosion  produced  by  the 
scillitin,  being  wanting  after  death  from  the  extract.  C.  Lupinski7  found  that 
scillitoxin  is  a  powerful  stimulant  to  the  peripheral  vagi  in  the  frog,  causing  slowing 
of  the  pulse,  and  in  certain  doses  diastolic  cardiac  arrest,  and  in  the  dog  slowing 
of  the  heart.  Large  doses  cause  in  the  frog  tetanic  contractions  of  the  heart.  He 
also  found  that  in  the  dog  large  doses  finally  paralyze  the  peripheral  vagi  and  pro- 
duce a  rapid  pulse.  The  arterial  pressure  is  increased,  partly,  it  is  affirmed,  by  the 
increased  cardiac  energy,  and  partly  by  a  peripherally  produced  vaso-motor  con- 
traction. 

It  is  certain  that  squill  contains  some  substance  which  acts  similarly 
to  digitalis  on  the  heart,  and  that  this  is  to  be  found  in  the  extract. 
Husemann  affirms  that  the  extract  has  no  expectorant  properties  ;  that  it 
is  a  digitalis-like,  cardiac  stimulant,  and  acts  as  a  diuretic  solely  by 
affecting  the  renal  circulation.  Squill  is  a  stimulant  to  the  kidneys,  and 
in  overdoses  causes  an  irritation  whose  result  is  lessening  of  the  secretion, 
scanty  bloody  urine,  or  absolute  suppression  of  urine,  according  to  the 
amount  of  the  poison  ingested.  Its  diuretic  action  has  been  noted  in 
animals  by  Schroff  and  by  Chiarenti  (quoted  by  Stille),  and  there  can  be 
no  doubt  as  to  the  power  that  squill  has  of  increasing  the  watery  portion 
of  the  urine.  We  know  of  no  studies  upon  its  action  on  the  urinary 
solids.  According  to  Stille,  the  external  application  of  squill  will  pro- 
duce its  characteristic  effects  on  the  system. 

It  is  a  valuable  remedy  in  dropsy  when  the  condition  of  the  system 
is  atonic  and  when  there  is  no  disease  of  the  kidney.  It  may  even  be 
used  with  advantage  in  serous  cffitsion  into  the  pleura  or  the  pericardium 
dependent  upon  chronic  inflammation  of  the  membrane,  especially  in 
combination  with  calomel.  A  pill  of  one  grain  each  of  squill  and  digi- 
talis is  very  efficient  in  cardiac  dropsy  ;  sometimes  the  addition  of  calomel 
is  advantageous.  The  one  centra-indication  to  the  use  of  squill  is  the 
existence  of  Bright' s  disease  or  of  acute  irritation  of  the  kidney. 

TOXICOLOGY. — According  to  Husemann,8  twenty-four  grains  of  squill 
have  caused  death.  The  treatment  of  the  poisoning  consists  in  the  evac- 
uation of  the  stomach  and  bowels  by  ipecacuanha  and  castor  oil,  if  nature 


682  LOCAL   REMEDIES. 

has  not  already  fulfilled  the  indication ;  the  free  use  of  opium ;  the  exhi- 
bition of  large  quantities  of  water,  for  its  action  on  the  kidneys  ;  and  the 
usual  measures  for  the  relief  of  gastro-enteritis,  if  much  tenderness  be 
present.  Early  in  the  poisoning  care  should  be  exercised  in  the  exhibi- 
tion of  alcoholic  stimulants,  for  fear  of  increasing  the  gastric  irritation  ; 
during  the  stage  of  collapse  they  may  be  imperatively  demanded,  and 
with  their  use  should  be  combined  that  of  dry  heat  applied  externally, 
and  of  the  other  usual  measures  of  relief  during  collapse. 

ADMINISTRATION. — As  a  diuretic,  squill  should  be  given  in  solid 
form,  one  or  two  grains  (0.06-0.12  Gm. )  every  three  hours,  the  dose 
being  gradually  increased  until  some  nausea  is  felt.  The  preparations 
of  squill  are  the  tincture  (TINCTURA  SCILL^E — ten  per  cent.,  U.  S.), 
— dose,  ten  to  twenty  minims  (0.6-1.2  C.c. )  ;  the  vinegar  (ACETUM 
SCILL^E — ten  per  cent.,  U.S.), — dose,  ten  to  twenty  minims  (0.6-1.2 
C.c.)  ;  the  syrup  (SYRUPUS  SCILL.E,  U.S.), — dose,  half  to  one  flui- 
drachm  (2-4  C.c.)  ;  and  the  fluid  extract  (FLUIDEXTRACTUM  SCILL^E, 
U.  S. ),— dose,  one  to  three  minums  (0.06-0.18  C.c.). 

SCOPARIUS— BROOM.     U.  S. 

Scoparius  is  the  dry  tops  of  Cytisus  Scoparius,  or  the  common  broom- 
plant  of  Europe,  which  is  cultivated  in  this  country  and  has  in  some 
places  escaped  from  the  gardens.  It  occurs  as  greenish  twigs,  with 
minute  downy  leaves,  has  a  bitter  nauseous  taste,  and,  when  bruised,  a 
peculiar  odor,  and  yields  its  virtues  to  hot  water.  Stenhouse  discovered 
in  scoparius  a  neutralized  crystallizable  principle,  Scoparin,  which  prob- 
ably represents  the  purgative  and  diuretic  influences  of  the  drug,  and  also 
a  liquid  alkaloid,  Sparteine.  (See  page  350). 

In  overdoses,  scoparius  causes  free  purging,  and  even  vomiting  ;  but 
as  ordinarily  administered  it  is  an  efficient  hydragogue  diuretic,  which  is 
much  used  in  general  dropsy,  and  is  one  of  the  most  reliable  remedies  of 
its  class.  It  is  best  given  in  decoction, — half  an  ounce  of  the  tops  in  a 
pint  of  water  boiled  down  to  half  a  pint ;  of  this  an  ounce  may  be  given 
every  three  hours  until  some  effect  is  produced  ;  or  a  fluid  extract,  which 
is  not  official,  may  be  given  in  half-drachm  doses. 

CALOMEL. — Many  years  ago  therapeutic  writers,  notably  George  B. 
Wood,  asserted  that  the  combination  of  digitalis,  squill,  and  calomel 
yields  in  the  treatment  of  dropsy,  and  especially  of  cardiac  dropsy,  diu- 
retic results  much  superior  to  either  of  the  vegetable  products  alone  ;  but 
more  recently  E.  Jendrassik9  directed  attention  to  the  great  practical 
value  of  calomel  as  a  diuretic. 

The  theory  that  mercury  acts  by  increasing  the  amount  of  urea  and 
thus  provoking  increased  diuresis  is  hardly  tenable.* 

*  See  Noel  Paton  (Brit.  Med.  Journ.,  1886,  ii.). 


DIURETICS.  683 

The  present  experimental  evidence  in  regard  to  the  effect  of  mercury 
upon  diuresis  in  the  lower  animals  is  contradictory.  W.  Cohnstein10 
affirms  that  the  hypodermic  injection  of  the  mercurial  produces  very  quick 
active  diuresis  in  the  rabbit,  but  Vejun-Tyrode  and  Nelson  M  failed  to  get 
a  consistent  diuretic  action  either  in  the  dog,  cat,  or  in  the  rabbit ;  as 
they  affirm  that  ' '  throughout  all  these  experiments  there  were  evidences 
of  more  or  less  severe  renal  irritation  as  shown  by  the  presence  of  blood 
and  casts  and  by  diuresis, "  it  is  probable  that  they  employed  the  calomel 
in  too  large  doses. 

According  to  Brasse  and  Wirth,11  when  mercury  is  given  hypodermic- 
ally  in  large  dose  it  soon  appears  in  the  urine,  which  is  markedly  in- 
creased in  quantity  ;  if,  as  not  rarely  happens,  the  urine  becomes  albu- 
minous, excretion  of  mercury  at  once  ceases,  albumin  and  mercury  never 
coexisting  in  the  urine.  Silva,12  experimenting  with  defibrinated  blood, 
finds  that  the  addition  of  a  mercuric  salt  causes  the  kidney  vessels  to 
dilate,  the  local  blood-pressure  to  rise,  and  secretion  to  increase.  More- 
over, it  is  certain  that  mercurials  in  excess  cause  desquamative  nephritis  ; 
so  that  it  must  be  concluded  that  these  preparations  either  stimulate  or 
irritate  the  renal  secretory  structure  proportionately  to  the  amount  present. 
According  to  Bieganski,  the  diuretic  effect  is  most  active  after  subcuta- 
neous injections  and  least  so  after  inunctions. 

The  destruction  of  renal  secreting  tissue  by  disease  without  doubt 
interferes  with  the  diuretic  action  of  mercurials,  but  the  fact  remains  that 
in  chronic  parenchymatous  nephritis  with  alarming  decrease  in  the  secre- 
tion of  urine,  calomel  is  one  of  the  most  effective  diuretics  known.  In 
cardiac  dropsy  it  is  often  very  efficient  in  improving  not  only  the  dropsy 
itself  but  the  condition  of  the  digestive  organs.  In  some  cases  of  chronic 
cardiac  disease  the  continued  use  of  minute  doses  of  the  mercurial  is  very 
advantageous,  but  when  it  is  desired  powerfully  to  affect  the  kidneys 
large  doses  of  the  drug  are  required.  Under  these  circumstances,  we 
have  found  the  administration  of  five  grains  of  calomel  every  two  hours 
until  fifteen  grains  in  all  are  taken  to  act  most  happily.  It  is  sometimes, 
though  rarely,  necessary  to  use  opium  to  check  the  purgative  action  of  the 
calomel.  When  there  is  excessive  debility  some  caution  may  be  necessary 
in  this  use  of  mercurials,  but  we  have  seen  life  apparently  saved  for  the  time 
being  by  the  removal  of  an  acute  suppression  of  wine  in  advanced  Bright 's 

disease. 

XANTHIN  COMPOUNDS. 

Xanthin,  or  Dioxypurin,  yields  the  following  compounds  which  are 
interesting  therapeutically  : 

First,  Trimethylxanthin  or  Caffeine,  which  we  have  already  fully 
considered. 

Second,  three  isomeric  dimethylxanthins  : 

i. — Dimethylxanthin,  Theobromine  ; 

2. — Dimethylxanthin,  Theophyllin  (Theocin)  ; 

3. — Dimethylxanthin,  Paraxanthin. 


684  LOCAL    REMEDIES. 

Dimethyl.ranthin  or  Theobrominc  has  been  chiefly  used  in  the  form 
of  the  sodium  thcobromine  salicylate,  a  white  powder,  soluble  in  less  than 
half  its  weight  of  warm  water,  and  containing  about  forty-nine  per  cent,  of 
theobromine.  It  has  been  put  upon  the  market  as  a  proprietary  remedy 
under  the  name  of  Diuretin,  which,  according  to  analysis,  contains  from 
thirty  to  forty  per  cent,  of  theobromine.  Attention  was  first  called  to 
theobromine  as  a  practical  remedy,  in  1890,  by  C.  Gram13  and  Kouindig- 
Pomerantz. u 

PHYSIOLOGICAL  ACTION. — Theobromine  is  rapidly  absorbed,  and  has 
been  shown  by  the  studies  of  Albanese,83  Bondzynski  and  Gottlieb,15  and 
of  Kruger  and  Schmidt,84  to  be  eliminated  in  part  unchanged,  and  in  part 
in  the  form  of  methylxanthin.* 

General  Effects. — The  ordinary  dose  of  theobromine  causes  no  dis- 
tinct symptoms  in  man,  and  we  know  of  no  recorded  cases  of  poisoning 
by  it.  According  to  I.  M.  Sabashnikoff 16  large  doses  produce  in  the 
lower  animals  a  quickening  of  the  respiration,  which  is  followed  after  a  toxic 
dose  by  intense  dyspnoea,  high  temperature,  free  salivation,  vomiting, 
diarrhoea,  and  excessive  diuresis.  The  elevation  of  temperature,  which 
sometimes  amounts  to  4°  C. ,  is,  according  to  Sabashnikoff,  prevented  by 
previous  high  section  of  the  spinal  cord. 

The  detailed  physiological  action  of  the  drug  has  not  been  worked  out; 
according  to  Sabashnikoff  there  is  increased  irritability  of  the  motor  area 
of  the  cerebral  cortex,  and  upon  the  striated  muscles  the  drug  acts  as  does 
caffeine.  The  toxic  dose  lowers  the  arterial  pressure.  (Cohnstein,17  and 
Bock. )  Cohnstein  found  that  the  full  therapeutic  doses  had  no  percepible 
influence  upon  the  blood-pressure,  and  in  Bock's  researches  the  pressure 
was  only  elevated  occasionally,  the  most  marked  phenomenon  being  great 
increase  in  the  frequency  of  the  pulse-rate,  probably  due  to  excitation  of 
the  accelerator  mechanism  of  the  heart,  since  the  vagi  was  found  to  be 
thoroughly  active.  As  the  result  of  studies  made  upon  the  isolated  heart 
of  the  mammal,  Bock  believes  the  fall  of  pressure  is  due  to  an  action  upon 
the  cardiac  muscles,  which  decreases  its  elasticity.  He  also  believes  that 
the  rise  of  pressure,  sometimes  produced  by  the  small  doses,  is  the  result 
of  the  increased  pulse  frequency. 

Kidney. — In  the  oncometrical  studies  of  Gottlieb  and  Magnus,103  the 
increased  diuresis  was  accompanied  by  an  increase  of  the  size  of  the 
kidney.  In  the  chloralized  animal  these  investigators  found  that  the  in- 
creased diuresis  persisted,  although  the  kidney  was  markedly  below  its 
normal  size, — evidence  that  the  diuresis  is  the  outcome  of  a  direct  action 
upon  the  secretive  power  of  the  kidney. 

THERAPEUTICS. — Theobromine  has   been   much   used  as  a  diuretic 

*The  researches  mentioned  show  that  the  exact  form  of  elimination,  as  well  as  the  per- 
centage of  the  various  educts,  varies  in  different  species  of  animals,  and  very  probably  in 
different  individuals  under  varying  circumstances.  In  man,  3-methylxanthin  seems  to  be 
the  chief  educt,  though  y-methylxanthin  (Heteroxanthin)  has  been  found  ;  whilst  in  rabbits 
7-methylxanthin  is  especially  produced. 


DIURETICS.  685 

which  is  not  irritant  to  the  kidneys,  and  rarely  causes  disagreeable  symp- 
toms. It  has  been  given  in  acute  and  chronic  nephritis  with  excellent 
results,  and  has  been  especially  recommended  in  cardiac  dropsy,  with  the 
statement  that  it  increases  the  force  and  regulates  the  character  of  the 
cardiac  beat  when  the  heart  is  weak.  (See  Masius,  also  Pawinski.18)  In 
rare  cases  it  acts  unfavorably,  causing  headaches,  irregularity  of  the  pulse, 
vomiting,  diarrhoea,  and  even — according  to  W.  Schmieden — haematuria. 
From  eighty  to  one  hundred  and  twenty  grains  (6—8  Gm.)  maybe  admin- 
istered during  the  course  of  the  day,  in  capsules  or  solution,  or  hypoder- 
mically.  According  to  Demme,  to  a  child  six  years  old  twenty  to  thirty 
grains  (1.3—2  Gm. )  may  be  given  in  the  twenty-four  hours. 

AGURIN  is  a  white,  slightly  bitter  powder,  freely  soluble  in  water,  which  is  said 
to  consist  of  five  parts  of  theobromine  acetate  and  two  parts  of  sodium  acetate.  It 
should  always  be  prescribed  in  the  form  of  the  powder,  its  solution  not  being 
stable,  but  should  be  taken  in  dilute  solution  in  doses  of  ten  to  fifteen  grains,  three 
or  four  times  a  day.  In  Mosauer's98  experiments  agurin  seemed  to  be  more  irri- 
tant to  the  kidneys  than  theobromine. 

Concerning  Paraxanthin  we  have  not  very  much  information,  but,  according 
to  Dreser-Elberfeld,  it  acts  in  a  manner  similar  to  theocin,  increasing  the  output  of 
urinary  solids  as  much  as  does  that  drug,  but  not  having  nearly  as  powerful  an  in- 
fluence in  the  excretion  of  water  from  the  kidneys. 

Theophyllin  or  Theocin  was  first  isolated  from  the  tea-leaf  by  Kossel,  but  in 
such  minute  quantities  as  not  to  be  a  commercial  product  until  the  discovery  by 
Traube  that  it  could  be  produced  by  synthesis  resulted  in  its  being  put  upon  the 
market  under  the  name  of  Theocin.  It  is  a  crystalline  substance,  soluble  in  one 
hundred  and  seventy-nine  parts  of  water  at  18°  C.,  in  eighty-five  parts  at  37°  C.  It 
was  first  brought  forward  by  Minkowski,91  as  a  very  active  diuretic,  and  has  been 
reported  upon  by  a  number  of  German  clinicians.  According  to  C.  Doering,  it  is 
about  as  poisonous  as  caffeine,  but  Doering,92  Thienger,91  and  Kramer,94  all  agree 
that  it  is  much  more  active  as  a  diuretic  than  is  either  caffeine  or  theobromine,  in- 
creasing remarkably  both  the  excretion  of  water  and  solid  matters  from  the  kidney. 
It  has  been  tried  both  in  cardiac  and  renal  dropsies  and  is  found  to  be  very  posi- 
tive in  its  influence.  Not  rarely  theocin  has  produced  disagreeable  symptoms,  the 
most  common  of  which  are  those  of  gastric  irritation  ;  in  some  cases  severe  vomit- 
ing, headache  and  general  malaise  have  been  reported  ;  and  Schlesinger  in  two 
cases  noted  the  occurrence  of  epileptiform  convulsions  after  the  taking  of  five 
doses  of  o.  2  gramme  of  theocin.  The  effect  of  theocin  is  also  apt  to  be  fugacious, 
the  system  apparently  in  a  short  time  becoming  accustomed  to  its  use,  so  that  it 
fails  to  cause  diuresis.*  Its  maximum  effect  is  commonly  apparent  the  second  or 
third  day  of  its  ingestion.  In  order  to  avoid  gastric  irritation,  it  is  better  to  give  in 
frequent  small  doses  up  to  from  7.5  to  8  grains  a  day  (0.5-1.2  Gm. ). 

SPIRITUS  ;£THERIS  NITROSI.  U.  S. — When  given  in  a  single  large 
dose  (a  teaspoonful  to  a  tablespoonful)  and  the  patient  afterwards  kept 
cool,  sweet  spirit  of  nitre  acts  as  a  feeble  diuretic,  at  the  same  time 

*  Albanese83  believes  that  the  rapid  diminution  of  diuresis  after  the  administration  of 
theocin  is  due  to  the  deposit  in  the  renal  canaliculi  of  crystals  of  trimethylxanthin  ;  basing 
his  belief  upon  microscopic  studies,  and  upon  the  fact  that  he  was  enabled,  by  injecting 
large  quantities  of  saline  solution  in  the  lower  animals,  to  maintain  the  activity  of  the 
drug. 


686  LOCAL   REMEDIES. 

soothing  the  kidneys.  It  is  often  useful  when  there  is  slightly  diminished 
renal  excretion  of  functional  origin,  or  when  the  kidneys  suffer  from  slight 
congestion,  as  shown  by  aching  in  the  loins. 

DIGITALIS,  in  its  general  relations,  has  already  been  sufficiently  dis- 
cussed, and  it  remains  only  to  speak  of  its  employment  as  a  diuretic. 
In  the  first  place,  it  should  be  distinctly  understood  that  it  has  no 
alterative  effect  whatever,  either  upon  the  nature  of  the  secretion  or 
upon  the  mucous  membrane  over  which  that  secretion  flows.  In  other 
words,  when  it  has  any  effect  it  is  purely  a  hydragogue  diuretic,  simply 
increasing  the  watery  portion  of  the  urine.  That  digitalis  has  direct 
diuretic  properties  cannot,  we  think,  be  doubted.  Nor  does  it  seem  less 
certain  that  it  varies  greatly  in  their  exercise,  so  that  when  given  to 
persons  in  health  it  will  sometimes  produce  free  diuresis  and  will  at 
other  times  fail  to  do  so.  Another  point  to  be  constantly  borne  in 
mind  during  its  administration  is  the  fact  that,  like  all  the  other  effects 
of  digitalis,  diuresis  is  very  slowly  induced,  and  is  very  persistent  when 
produced  by  the  ordinary  cautious  method  of  administration.  The 
diuresis  of  digitalis  is  not  simply  a  result  of  its  action  on  the  circula- 
tion, since  it  will  sometimes  appear  before  the  circulation  is  sensibly 
affected.  At  the  same  time,  it  is  very  evident  that  in  disease  the  good 
effect  of  digitalis  upon  the  renal  organs  is  often  in  large  measure  due 
to  its  action  upon  the  heart.  Thus,  in  dropsy  from  a  dilated  heart  the 
renal  gland-cells  cannot  secrete  because  they  are  not  supplied  with  the 
proper  kind  and  quantity  of  blood,  their  circulation,  like  that  of  the 
remainder  of  the  body,  being  nearly  stagnant.  If  under  these  circum- 
stances digitalis  be  exhibited,  and  the  circulation  becomes  compara- 
tively free  and  active,  the  resultant  diuresis  is  wrought  out  through  a 
double  mechanism,  partly  indirectly  and  partly  directly  produced  by 
the  drug.  As  a  consequence  of  these  facts,  clinicians  have  long  since 
practically  determined  that  digitalis  is  especially  valuable  as  a  diu- 
retic in  cardiac  dropsy.  Digitalis  is  also  very  useful  in  renal  dropsy, 
both  in  the  subacute  and  in  the  chronic  form.  Of  course,  like  every- 
thing else,  it  frequently  fails  in  these  varieties  of  Bright' s  disease,  but 
certainly  it  should  always  be  tried.  In  acute  suppression  of  urine  the 
external  application  of  digitalis  is  often  efficient.  Flannels  wrung  out  of 
the  infusion,  or  containing  an  ounce  of  the  tincture,  may  be  applied  to  the 
abdomen  and  covered  with  oil-silk.  Some  practitioners  prefer  poul- 
tices made  directly  of  the  leaves.  Lente 19  says  that  he  has  been  accus- 
tomed to  use,  even  in  children,  four  ounces  of  the  best  English  leaves, 
and  with  a  quart  of  water  ' '  make  a  poultice  which  extends  all  round  the 
body,  and  from  the  thorax  to  the  pelvis."  The  application  should  not 
be  left  on  for  more  than  from  eight  to  ten  hours,  and  only  in  desperate 
cases  should  very  large  amounts  be  employed,  as  the  external  use  of  a 
single  ounce  of  the  tincture  has  caused  almost  fatal  collapse.* 

*  Case  of  E.  F.  Fannell  (Brit.  Med.  Journ.,  March,  1871). 


DIURETICS.  687 

The  dose  of  the  powder  of  digitalis,  as  a  diuretic,  is  three  grains 
(0.2  Gm.)  a  day  (in  divided  doses),  increased  by  a  grain  every  second 
or  third  day,  until  some  sensible  effects  are  manifested.  The  infusion 
or  the  tincture  may  be  substituted  for  the  powder,  in  corresponding 
dose.  Digitalis,  in  the  majority  of  cases,  is  best  given  in  combination  : 
in  cardiac  dropsy  it  is  much  more  efficient  if  given  with  squill ;  in  renal 
diseases  the  potassium  bitartrate  may  be  exhibited  simultaneously. 

Jaborandi,  Strophanthus ,  and  Caffeine  are  active,  practical  diuretics. 
(See  respective  articles.) 

SUGAR. — In  the  last  few  years  it  has  been  affirmed  by  S.  Meslach, 
Zavadsky,  Germain-Se'e,  and  other  clinicians  that  both  glucose  and  the 
sugar  of  milk  are  active  hydragogue  diuretics,  which  may  often  advan- 
tageously be  used  in  the  treatment  of  cardiac  dropsy,  pleuritic  effusions, 
etc.,  but  are  of  little  value  when  there  is  renal  disease.  The  general 
testimony  seems  to  be  that  the  sugar  of  milk  is  the  more  active  of  the 
two.  These  sugars  may  be  given  in  doses  of  from  one  to  six  ounces 
(30-180  Gm. )  a  day,  administered  in  concentrated  syrup  or  in  milk. 
How  sugar  under  these  circumstances  acts  as  a  diuretic,  or  whether  it  has 
any  influence  upon  the  nervous  system  and  circulation,  is  at  present 
doubtful.  According  to  the  experiments  of  Albertoni,  all  sugars  injected 
into  the  veins  cause  a  rise  of  the  arterial  pressure  by  a  direct  stimulation 
of  the  heart.  He  also  found  that  the  kidneys,  as  tested  by  Roy's 
oncometer,  become  congested  or  swollen. 

DEPURANT   DIURETICS. 

POTASSIUM. 

On  account  of  the  physiological  activity  of  potash  as  a  base,  it  exerts 
great  influence  upon  the  physiological  activity  of  its  salts.  These,  for 
our  present  purposes,  may  be  well  divided  into  the  vegetable  salts,  in- 
cluding the  carbonates,  and  the  mineral  salts.  The  mineral  salts  of  potash 
are  all  of  them  powerful  local  irritants,  and  most  of  them  are  capable  of 
taking  life  when  given  in  overdose.  As  therapeutic  agents  they  have  to 
be  studied  separately.  The  official  vegetable  salts  of  potash,  with  the 
exception  of  the  bi-tartrate,  act  similarly  upon  the  system,  varying  al- 
most solely  in  that  some  are  more  irritant  than  others. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Caustic  potash  is  a  pow- 
erful escharotic,  and  many  of  its  vegetable  salts  are  more  or  less  irritant. 
These  salts  are  also  powerful  depressants  probably  of  all  of  the  higher 
tissues. 

Astalfoni %  found  that  when  locally  applied  to  the  brain  cortex,  to  the  spinal 
cord,  to  the  peripheral  nerves,  or  to  the  muscles,  the  potash  salts  produce  a  very 
pronounced  lessening  of  irritability.  When  very  weak  solutions  were  employed 
this  condition  of  depression  was  often  preceded  by  one  of  excessive  irritability, 
but  when  solutions  of  five  per  cent,  were  used,  no  such  stage  was  observable. 


688  LOCAL    REMEDIES. 

The  effects  of  the  ordinary  therapeutic  doses  of  the  potash  salts  upon 
the  human  system  are  not  sufficiently  obvious  to  be  perceived  by  the 
clinical  observer.  Only  when  a  single  dose  is  overwhelmingly  large, 
or  when  by  long  continued  use  there  has  been  an  accumulation  of  potash 
in  the  system,  are  there  such  obvious  results  as  general  muscular  weak- 
ness, lowered  temperature,  depression  of  the  circulation,  dyscrasia,  and, 
it  may  be,  even  excessive  fluidity  of  the  blood.  With  many  of  the  pot- 
ash salts  the  local  irritant  influence  upon  the  alimentary  canal  and  the 
kidneys  may  overshadow  the  other  phenomena  of  the  poisoning.  In  the 
lower  animals  potash  and  its  vegetable  salts  in  toxic  dose  produce  de- 
pression of  the  circulation,  fall  of  temperature,  lessening  of  both  voluntary 
and  reflex  movements,  and  finally  death  from  cardiac  paralysis. 

Neuro-muscidar  System. — Podocaepow20  believed  that  the  action 
of  potash  salts  in  the  frog  is  chiefly  upon  the  muscles,  but  the  experi- 
ments of  Guttmann,  of  Ringer  and  Morshead,21  and  of  Ringer  and  Mur- 
rell,"  have  definitely  proven  that  the  brain,  the  spinal  cord,  the  motor 
and  sensory  nerves,  and  the  muscles  are  all  attacked  by  potash.  Ac- 
cording to  Ringer  and  Murrell,  the  spinal  cord  and,  next  to  it,  the 
brain  are  the  most  sensitive  to  the  action  of  the  drug. 

Circulation. — Our  knowledge  of  the  action  of  the  small  dose  of  pot- 
ash salts  upon  the  circulation  is  very  imperfect,  but  there  is  considerable 
testimony  to  show  that  such  dose  produces  rise  in  the  arterial  pressure. 

If  there  be  a  rise  of  pressure  produced  by  the  minute  doses  of  the  chloride  it 
would  seem  probable  that  it  is  due  to  an  action  upon  the  blood-vessel  walls,  since 
Boltazi 95  found  it  impossible  by  any  dose  of  the  potash  salts  to  increase  the  work 
done  by  the  frog's  heart ;  and  in  the  experiments  of  Astalfoni,  injection  of  minute 
doses  of  the  potash  through  the  blood-vessels  of  the  kidney  or  of  one  exsected  leg 
caused  contraction  of  the  arterioles.  Traube 2S  asserts  as  the  result  of  his  experi- 
ments that,  injected  into  the  blood  in  doses  of  two  or  three  grains,  the  potassium 
nitrate  produces  a  fall  in  the  pulse  and  a  rise  in  the  arterial  pressure.  Aubert  and 
Dehn  have  experimented  with  a  number  of  the  salts  of  potassium,  and  found  that, 
with  the  exception  of  the  permanganate,  they  all  act  upon  the  circulation  in  the 
manner  just  described.  It  remains  at  present  writing,  however,  doubtful  whether 
the  rise  of  pressure  just  spoken  of  is  a  direct  phenomenon  caused  by  potash.  No 
dose  of  a  potash  salt  ever  calls  forth  symptoms  of  circulatory  stimulation  from  the 
human  body.  Further,  Podocaepow  and  also  Aubert  and  Dehn  affirm  that  the 
rise  following  the  potash  injection  in  the  animal  usually  lasts  only  three  minutes, 
and  that  in  no  case  is  the  maximum  effect  perceptible  for  more  than  ten  minutes. 
Aubert  and  Dehn  further  assert  that  there  is  no  cumulative  action,  the  repetition  of 
small  doses  of  the  drug  at  brief  intervals  leaving  no  residual  effect,  the  pressure  re- 
turning to  the  normal  after  each  injection,  just  as  though  no  previous  injection  had 
been  given.  The  correctness  of  this  statement  remains  doubtful,  since  Guttmann 
asserts  that  there  is  a  gradual  rise  of  pressure. 

Full  doses  of  potassium  greatly  and  progressively  lower  the  arterial 
pressure,  and  this  is  the  only  influence  of  the  potash  salts  upon  the  cir- 
culation which  is  clinically  demonstrable.  The  fall  of  pressure  is  very 
largely  due  to  the  direct  action  of  poison  upon  the  heart,  but  there  can 


DIURETICS.  689 

be  no  doubt  that  the  muscle-fibres  of  the  blood-vessels  are  also  de- 
pressed, so  that  the  blood-pressure  is  reduced  by  the  conjoint  depression 
of  the  muscle-fibres  of  the  heart  and  blood-vessels.  This  action  is  shown 
by  Dogiel M  to  be  a  portion  of  the  wide-spread  general  muscular  influence 
of  the  poison,  the  heart  muscle  and  the  arterial  muscle-fibres  being  sim- 
ply more  sensitive  to  the  influence  of  potash  than  are  the  skeletal  and  in- 
testinal muscles.  The  heart  is  usually  arrested  in  diastole  (Podocaepow 
and  Guttmann),  and  as  pointed  out  by  Traube,  its  muscle  may  be  unable 
to  respond  to  electrical  stimulation.* 

According  to  Aubert  and  Dehn,"  for  a  few  seconds  before  complete  suspen- 
sion of  cardiac  movements  there  are  irregular,  "stormy"  convulsions,  which  run 
through  the  heart  in  a  sort  of  peristalic  manner  with  great  rapidity,  but  have  no 
effect  in  expelling  the  blood. 

The  observations  of  Aubert  and  Dehn,  that  the  effect  of  the  potash  is  not  per- 
manent unless  it  is  continued  a  certain  length  of  time,  is  in  accord  with  that  of 
Astalfoni,  who  found  in  using  potash  locally  that  functional  irritability  could  be 
restored  by  washing  out  the  part  with  a  weak  solution  of  sodium  phosphate.  Podo- 
caepow K  and  Guttmann  have  found  that  in  fatal  poisoning  the  contractility  of  the 
cardiac  muscle  may  be  in  a  measure  preserved  if  the  potash  salt  has  been  very 
slowly  introduced  into  the  circulation. 

The  method  by  which  the  changes  in  the  pulse  are  produced  by  the  small  dose 
of  potash  also  remains  uncertain.  Traube  affirms  that  if  the  vagi  be  cut  after  ex- 
hibition of  the  potash  salt,  the  lessened  pulse-rate  instantly  becomes  rapid,  and  the 
already  increased  arterial  pressure  rises  still  further.  The  same  observer  also 
found  that  after  section  of  the  pneumogastrics  small  doses  of  the  nitrate  produced 
a  fall  in  the  pulse,  with  increased  arterial  pressure  ;  but  on  a  repetition  of  the  dose 
in  the  same  animal  no  lessening  of  the  pulse-frequency  was  perceptible,  while  each 
time  the  pressure  rose.  This  seems  to  indicate  that  the  cardiac  action  of  the  drug 
is  independent  of  the  inhibitory  apparatus,  which  is  confirmed  by  the  experiments 
of  Aubert  and  Dehn  upon  atropinized  dogs. 

Section  of  the  vagi,  according  to  Guttmann,  has  no  influence  upon 
the  action  of  the  poison,  and  it  seems  to  be  established  that  the  depres- 
sion of  the  cardiac  muscle  is  by  a  direct  action  of  the  salt  upon  the 
muscle  itself. 

Influence  upon  Nutrition. — Outside  of  the  body,  potassium  favors  very 
greatly  the  oxidation  of  organic  substances.  Thus,  when  albumin  or 
haematin  is  dissolved  in  water  no  change,  or  a  very  slow  one,  occurs,  but 
if  potash  be  added  the  organic  principle  is  oxidized  with  extraordinary 
rapidity.  There  is  now  sufficient  evidence  to  establish  the  original  theory 
of  Lehman,  that  this  oxidizing  influence  is  exerted  by  these  salts  in  the 
living  body.  The  fall  of  temperature  produced  by  poisonous  doses  of 
potassium  salts  is  probably  due  to  excessive  loss  of  heat  caused  by  loss  of 


*  The  poisonous  influence  of  potash  upon  the  heart  was,  we  believe,  first  discovered 
by  Black  (Comptes-Rendtts,  1839),  and  has  been  confirmed  by  Bouchardat  (Antiuaire  de 
Therapeutique,  1844),  by  Grandeau  ( Robin's  Journal  de  I' Anatomic,  1864),  by  Rabuteau 
{U  Union  Medicate,  1871),  and  by  others. 

44 


69o  LOCAL    REMEDIES. 

tone  in  the  blood-vessels.  That  there  is  under  the  influence  of  the 
alkali  a  great  increase  of  nitrogenous  elimination  both  in  health  and 
disease  seems  to  be  fairly  proved. 

In  an  elaborate  series  of  experiments  upon  himself,  E.  A.  Parkes 27  found  that 
liquor  potassae  (two  fluidrachms)  when  taken  fasting,  produced  in  from  thirty  to 
ninety  minutes  an  increased  flow  of  slightly  acid  urine  containing  the  whole  of  the 
alkali  and  organic  matter,  which  differed  in  quality  from  that  ordinarily  found  in 
urine,  and  was  also  larger  in  amount  than  normal.  An  organic  acid,  certainly 
neither  uric  nor  hippuric,  was  believed  to  form  a  part  of  the  solid  matter  by  Parkes, 
who  attributes  the  alteration  of  the  urinary  solids  to  the  oxidizing  influence  of  the 
potash.  Taken  after  meals,  the  liquor  potassae  acted  simply  as  an  antacid,  and  had 
no  perceptible  effect  upon  the  urine.  Both  potassium  acetate  and  nitrate  in  Parkes' s 
experiments  failed  to  act  on  the  urine,  probably  because  taken  in  too  small  doses, 
for  it  is  a  fair  presumption  that  their  oxidizing  influence  is  less  than  that  of  potash 
itself.  Certainly  other  experimenters  have  determined  that  they  do  influence  the 
urinary  excretion.  Golding  Bird  M  found  that  in  a  case  carefully  tested,  under  favor- 
able circumstances,  three  drachms  of  potassium  acetate  increased  the  solids  of  a  dog's 
urine  from  four  hundred  and  sixteen  to  seven  hundred  and  eighty-two  grains,  or, 
deducting  all  the  eliminated  potash,  to  over  six  hundred  grains.  The  increase  of  the 
uric  acid  was  about  thirty-two  per  cent. ;  of  the  urea,  about  sixty  per  cent. ;  of  ex- 
tractives, including  kreatine,  kreatinine,  etc. ,  about  twenty  per  cent. ;  or,  speaking 
absolutely,  the  uric  acid  was  increased  eighty-five  grains,  the  urea  seventy-two 
grains,  and  the  extractive  thirty-six  grains.  Rabuteau w  found  that  the  daily  in- 
gestion  of  seventy-five  grains  of  potassium  chloride  caused  an  increase  of  twenty 
per  cent,  in  the  amount  of  urea  discharged.  Aug.  Dehn  M  has  also  experimentally 
found  that  the  potassium  salts  greatly  increase  the  elimination  of  urea. 

The  conclusion  reached  by  experimental  research  made  upon  healthy 
men  and  animals — namely,  increased  tissue-change  as  the  result  of  potash 
ingestion — is  in  close  concord  with  those  upon  diseased  organisms. 

In  six  observations  upon  subjects  affected  with  what  may  be  termed  indifferent 
diseases,  such  as  lead  palsy,  Parkes 31  found  that  the  urea  was  increased,  and  also 
the  sulphuric  acid,  by  the  use  of  drachm  doses  of  liquor  potassae.  Austin  Flint J2 
has  studied  the  effect  of  potassium  nitrate  upon  a  number  of  persons  suffering  from 
various  diseases,  and  found  that  it  very  greatly  increases  the  amount  of  solids 
in  the  urine.  In  rheumatism  Parkes  found  that  liquor  potassae  increased  the 
elimination  of  sulphuric  acid,  but  had  no  decided  influence  on  the  uric  acid.  He, 
however,  used  such  small  doses  of  the  drug  as  not  to  get  the  effect  obtained  in  the 
alkaline  treatment  of  the  disease,  since  he  expressly  states  that  the  urine  remained 
acid.  Rheumatism,  gout,  and  the  uric  acid  diathesis  certainly  bear  some  relation 
with  one  another.  It  has  long  been  customary  to  use  potash  salts  in  excess  of  uric 
acid  in  the  urine,  and  the  relief  obtained  has  been  believed  to  be  due  to  the  conver- 
sion of  the  acid  into  a  urate.  Basham  M  affirms,  however,  that  as  the  result  of  a 
series  of  analyses  he  has  found  that  in  uric  acid  diathesis  not  only  is  there  a  great 
increase  of  the  urea  during  the  use  of  potash,  but  also  that  the  uric  acid,  either 
free  or  combined,  in  the  urine  is  greatly  diminished.  Basham,  remembering  that 
Schunck  had  proved  that,  under  the  oxidizing  power  of  potash,  uric  acid  outside  of 
the  body  is  converted  into  oxaluric  acid,  which  in  its  turn  is  readily  metamorphosed 
into  oxalic  acid  and  urea,  carefully  examined  the  urine  of  gouty  patients  taking  the 
alkali,  and  found  that  not  only  was  the  urea  increased,  but  that  oxalic -acid  also 
appeared  as  the  uric  acid  decreased,  and  that  the  urine,  on  standing,  deposited 


DIURETICS.  691 

crystals  of  calcium  oxalate,  although  none  of  these  could  be  found  in  it  when  first 
voided.  This  research  of  Basham  certainly  seems  to  demonstrate  that  in  uric  acid 
diathesis  the  potassium  salt  increases  the  oxidation  and  the  ultimate  metamorphosis 
of  tissue. 

Rabuteau,  in  his  experiments  with  potassium  chloride,  found  that 
the  urine  maintained  its  acidity,  although  potassium  acetate,  carbon- 
ate, or  citrate  produced  alkalinity  of  the  urine.  A  plausible  explana- 
tion of  this  diversity  is  that  the  vegetable  acid  salts  are  oxidized  into 
carbonates  in  the  system,  while  mineral  acids  of  necessity  pass  through 
unaltered.  Thus,  from  the  urine  of  a  patient  taking  two  hundred  and 
seventy  grains  of  the  nitrate  daily,  Alfred  S.  Taylor34  obtained  158.7 
grains  of  the  ingested  salt  per  diem.*  If,  as  there  is  much  reason  to 
believe,  a  vegetable  acid  when  given  alone  passes  through  the  system 
in  great  measure  unchanged,  while,  as  asserted  by  Munch, 35  and  as  seems 
to  follow  from  the  facts  already  brought  forward,  the  same  acid  is  found 
when  combined  with  an  alkali  to  be  oxidized  and  converted  into  carbonic 
acid,  there  is  in  this  strong  corroboration  of  the  belief  that  the  potash 
salts  increase  oxidation  in  the  system.  Putting  all  the  evidence  together, 
it  seems  to  us  that  the  oxidation  theory  must  be  accepted  as  exceedingly 
plausible  and  probable,  although  not,  perhaps,  absolutely  proved. 

When  a  potassium  salt  is  given  in  large  doses  for  a  long  time,  it 
produces  a  condition  of  dyscrasia,  with  impoverishment  and  excessive 
fluidity  of  the  blood.  It  is  probable  that  there  is  some  connection 
between  these  changes  and  the  oxidizing  power  of  the  drug. 

POTASSII  CARBONAS.  U.  S. — Potash  of  commerce,  obtained  from 
wood-ashes  and  other  sources,  occurs  in  the  form  of  fused,  stony  masses, 
variegated  in  color,  and  of  a  caustic,  burning  taste  ;  when  purified  so  as 
to  form  pearlask,  it  becomes  of  a  bluish-white  color.  When  further 
purified  so  as  to  conform  with  the  official  tests,  it  occurs  as  a  coarse, 
granular,  whitish  powder,  very  deliquescent,  soluble  in  its  weight  of 
water,  insoluble  in  alcohol.  It  is  too  irritant  for  use  as  an  internal 
remedy. 

POTASSII  BICARBONAS.  U.  S.  —  Potassium  Bicarbonate  occurs  in 
transparent,  colorless  crystals,  not  deliquescent,  slightly  alkaline  to  the 
taste  and  to  test-paper.  It  dissolves  in  3. 2  parts  of  water  at  59°  F. ,  but 
is  insoluble  in  alcohol.  This  salt  may  be  used  as  an  antacid  or  to  increase 
the  liquidity  of  the  bile,  as  in  catarrhat  jaundice,  but  it  is  so  disagreeable 
to  the  taste  that  the  acetate  or  citrate  is  much  preferable  when  free  con- 
tinuous medication  of  the  general  system  is  desired.  Dose,  as  an  antacid, 
fifteen  to  thirty  grains  (1-2  Gm. ),  in  dilute  solution. 

*  A  portion  of  the  potassium  salts  escapes  through  the  intestines,  as  Kramer  (Annales 
cTHygi&ne  Publique  et  de  Mid.  Ltff.,  1843,  i.)  has  found  the  nitrate  in  the  faeces  of  animals 
taking  it ;  and  it  is  much  more  probable  that  the  nitrate  not  accounted  for  in  Taylor's 
investigation  was  eliminated  by  the  intestines  than  that  it  was  decomposed  in  the  system. 


692  LOCAL   REMEDIES. 

LIQUOR  POTASS^E.  U.  S. — Solution  of  Potassa  is  a  colorless,  water-like 
liquid,  of  a  strong,  acrid,  alkaline  taste,  and  is  made  by  boiling  a  solution 
of  the  potassium  bicarbonate  with  lime.  It  contains  only  five  and  eight- 
tenths  per  cent,  of  the  alkali,  but  is  capable,  in  overdose,  of  acting  as 
an  irritant  poison.  Dose,  ten  to  twenty  minims  (0.6-1.2  C.c.),  well 
diluted. 

POTASSII  CITRAS.  U.  S. — Potassium  Citrate  is  a  whitish,  granular, 
deliquescent  salt,  of  neutral  or  very  slightly  acid  reaction,  freely  soluble 
in  water.  It  is  the  least  offensive  to  the  palate  of  all  the  potassium  salts, 
except  the  tartrates.  The  Solution  of  Potassium  Citrate  (  LIQUOR  POTAS- 
SII CITRATIS,  U.  S. ),  has  long  been  used  as  a  diaphoretic  in  sthenic 
fevers.  The  dose  is  one-half  to  one  fluidounce  ( 1 5-30  C.  c. )  every  one  or 
two  hours. 

The  so-called  Effervescing  Draught !, — which  was  formerly  made  by 
preparing  two  solutions,  one  consisting  of  lemon-juice  and  water,  equal 
parts;  the  other  of  potassium  bicarbonate,  one  drachm,  water  three 
ounces;  an  ounce  of  each  of  the  solutions  to  be  put  together  and  drunk 
during  effervescence, — has  been  replaced  by  the  POTASSII  CITRAS  EFFER- 
VESCENS,  U.  S.  {Effervescent  Potassium  Citrate},  a  powder  which  must 
be  kept  in  well-stoppered  bottles,  which  contains  twenty  per  cent,  of 
potassium  citrate,  and  may  be  given  in  doses  of  sixty  to  one  hundred  and 
twenty  grains  (4-8  Gm.).  This  preparation  is  especially  useful  when  in 
fever  there  is  a  tendency  to  sick  stomach. 

POTASSII  ACETAS.  U.  S. — Potassium  Acetate  is  a  perfectly  neutral 
white  salt,  of  a  decidedly  saline  taste,  extremely  deliquescent,  and  solu- 
ble in  half  its  weight  of  water.  It  is  made  by  dissolving  the  bicarbonate 
in  acetic  acid,  and  evaporating.  It  occurs  sometimes  as  soft,  fibrous 
masses,  at  other  times  it  has  a  foliated  structure. 

THERAPEUTICS. — An  important  use  of  the  vegetable  salts  of  potas- 
sium is  in  acute  inflammatory  rJieumatism.  Before  the  introduction  of 
the  salicylates  the  alkaline  treatment  was  the  best  that  was  known  for 
cases  of  thoroughly  acute  rheumatism :  the  medicine  must  be  given 
freely,  an  ounce  to  an  ounce  and  a  half  in  the  day,  and  be  persisted  in  ; 
opium,  of  course,  being  at  the  same  time  employed  in  as  large  doses  as 
are  required  to  relieve  the  pain  :  after  a  few  days,  when  the  violence  of 
the  symptoms  has  abated  and  decided  anaemia  appears,  the  exhibition  of 
the  drug  should  be  discontinued  and  potassium  iodide,  with  tonics,  be 
substituted.  In  cases  subacute  from  the  beginning  a  combination  of  the 
potassium  iodide  and  acetate  is  sometimes  very  efficient,  ten  grains  of 
the  former  and  thirty  of  the  latter  being  administered  three  or  four  times 
a  day.  The  potash  probably  does  good  in  rheumatism  by  lowering 
arterial  action,  by  favoring  oxidation  and  elimination  of  partially  effete 
materials,  and  by  neutralizing  excessive  acidity. 


DIURETICS.  693 

As  depurants,  the  potash  salts  are  very  useful  in  various  diseases. 
Attention  has  been  especially  called  by  Golding  Bird  to  their  value  in 
that  class  of  cases  spoken  of  as  chronic  biliorisness.  In  chronic  malarial 
poisoning,  in  catarrhal  jaundice,  and  in  the  jaundice  of  simple  hepatic 
torpor  they  are  often  of  use.  In  uric  acid  gravel  and  in  uric  acid  cal- 
culus the  vegetable  salts  are  useful  in  checking  the  deposition  of  the  uric 
acid,  but  have  no  influence  upon  calculi  already  formed. 

ADMINISTRATION. — As  usually  exhibited,  the  potash  salts  are  ex- 
ceedingly distasteful.  There  is  no  need  of  this  whatever.  The  citrate 
may  be  given  dissolved  in  lemon-juice,  or,  what  is  a  still  more  pleasant 
method,  a  syrupy  solution  of  the  bicarbonate  and  the  citrate  may  be 
made,  of  such  a  strength  that  every  tablespoonful  of  it  shall  contain  half 
a  drachm  of  each  salt.  At  the  time  of  exhibition  one  or  two  tablespoon- 
fuls  of  this  may  be  put  in  a  little  water,  and  to  it  be  added  a  large  table- 
spoonful  of  lemon-juice,  the  whole  to  be  drunk  while  effervescing.  If  the 
patient  takes  in  the  course  of  the  day  six  of  the  largest  doses  mentioned, 
the  whole  amounts  to  an  ounce  and  a  half  of  potassium  citrate.  When 
the  remedy  is  used  simply  as  a  depurant,  as  in  jaundice,  such  large  doses 
are,  of  course,  not  proper  ;  a  teaspoonful  of  the  alkaline  solution,  with  a 
corresponding  amount  of  lemon-juice,  taken  three  times  a  day,  will  gen- 
erally be  sufficient. 

POTASSII  BITARTRAS.  U.  S. — Potassium  Bitartrate  occurs  in  white 
crystalline  crusts  or  masses,  which  are  commonly  pulverized  before  being 
sold  as  Cream  of  Tartar.  It  usually  contains  calcium  tartrate,  and  is 
only  sparingly  soluble  in  cold  water.  It  is  probably  eliminated  unchanged 
as  a  bitartrate,  and  certainly  differs  from  its  congeners  in  being  an  active 
hydragogue  diuretic  and  cathartic.  Half  an  ounce  to  an  ounce  (15-30 
Gm. )  of  it  given  at  once  will  very  generally  cause  watery  purging.  An 
ounce  (30  Gm. )  of  it  in  a  pint  of  infusion  of  juniper-berries,  taken,  in 
divided  doses,  during  the  twenty-four  hours,  will  very  often  act  most 
happily  in  dropsy.  In  acute  desquamative  nephritis,  cream  of  tartar  is 
often  very  serviceable  ;  as,  however,  the  avoidance  of  irritation  of  the 
kidneys  is  imperative  in  this  disease,  the  infusion  of  juniper  should  not 
be  used. 

POTASSII  SULPHAS.  U.  S. — Potassitim  Sulphate  occurs  in  small  aggre- 
gated, transparent,  very  hard  crystals,  permanent  in  the  air,  usually  short 
six-sided  prisms,  possessing  a  nauseous  somewhat  bitter  taste.  It  is  said 
to  be,  in  doses  of  four  or  five  drachms,  ' '  a  mild  purgative,  operating 
usually  without  heat  or  pain  or  other  symptoms  of  irritation,"  and  in 
doses  of  one  or  two  drachms  a  laxative.  It  is,  however,  a  powerful  irri- 
tant, and  we  have  never  seen  it  administered.  Mowbray  states  that  the 
salt  is  used  in  France  as  a  popular  abortifacient,  and  that  he  has  seen 
very  alarming  symptoms  produced  by  four  drachms  of  it.  Two  ounces 
have  caused  a  fatal  gastro-enteritis  (Taylor). 


694  LOCAL   REMEDIES. 

POTASSII  NITRAS.  U.  S. — Potassium  Nitrate,  or  Nitre,  is  ordinary 
saltpetre.  Chili  saltpetre  has  no  physiological  similitude  with  true  salt- 
petre, being  a  sodium  nitrate. 

Saltpetre  occurs  in  more  or  less  perfect,  long,  striated,  semi-trans- 
parent, six-sided  prisms,  with  dihedral  summits  ;  of  a  sharp,  saline, 
somewhat  cooling  taste  ;  containing  no  water  of  crystallization,  but  de- 
crepitating when  thrown  on  the  fire,  from  the  evaporation  of  water  me- 
chanically retained  in  the  crevices  of  the  crystals  ;  soluble  in  four  or  five 
times  its  weight  of  cold  and  in  two-fifths  of  its  weight  of  boiling  water, 
sparingly  soluble  in  proof  spirit,  insoluble  in  absolute  alcohol. 

PHYSIOLOGICAL  ACTION. — Potassium  nitrate  is  so  violently  irritant 
that  the  general  effects  of  the  potash  in  it  upon  the  system  are  lost  in  the 
local  symptoms  caused  by  its  overdose.  If  by  very  free  dilution  the 
local  irritant  influence  of  the  nitre  be  overcome,  the  poison  loses  much  of 
its  virulence  and  extraordinary  amounts  can  be  taken  without  serious 
results.  * 

The  symptoms  of  poisoning  by  potassium  nitrate  are  an  intense  burn- 
ing pain  in  the  stomach,  coming  on  in  a  few  minutes  after  the  ingestion 
of  the  poison,  and  soon  followed  by  violent  vomiting,  and,  it  may  be, 
free  purging,  with,  after  some  hours,  collapse,  great  muscular  weakness, 
and  not  rarely  local  convulsive  tremblings.  The  matters  vomited,  and 
even  the  stools,  may  be  bloody  (Husemann36).  Sometimes  the  ner- 
vous symptoms  predominate,  and  the  purging  may  be  absent :  col- 
lapse, with  slight  vomiting  and  with  or  without  paralysis  of  the  lower 
limbs,  may  alone  exist.  Suppression  of  urine  has  been  noted  in  some 
cases.*  After  death,  very  grave  lesions  are  found  in  the  stomach  and 
the  intestines,  such  as  intense  redness  and  congestion,  and  effusion  of 
blood  into  the  submucous  coat,  and  sometimes  into  the  stomach  itself. 
Even  ulceration  and  corrosion  of  the  mucous  membrane  have  been  ob- 
served. How  far  potassium  nitrate  acts  upon  the  blood  is  at  present 
uncertain  ;  Mairet  and  Combemale  assert  that  it  alters  the  red  blood- 
corpuscles.  Sometimes,  however,  death  has  occurred,  in  poisoning  by 
saltpetre,  with  great  suddenness.  In  the  only  cases  of  this  character  the 
record  of  which  we  have  read  the  dose  has  been  very  large,  and  it  is 
possible  that  the  death  has  been  the  result  of  the  paralyzing  action  of 
the  potash  upon  the  heart. 

Potassium  nitrate  is  of  no  value  as  an  internal  remedy,  having  been 
superseded  by  the  vegetable  salts  in  acute  rheumatism.  Its  local  action 
is  very  similar  to  that  of  the  chlorate. 

*  In  a  case  under  the  care  of  Wilks  (Guy's  Hasp.  Rep.,  3d  series,  1863,  ii.  173),  a  man 
suffering  from  renal  dropsy  took,  between  October  28  and  December  26,  1862,  one  pound 
twelve  ounces  and  six  drachms  of  potassium  nitrate,  with  benefit.  As  one  ounce  has 
caused  death  in  three  hours  (Taylor,  Medical  Jurisprudence,  2d  ed.,  i.  237),  this  patient 
received  in  fifty-nine  days  the  equivalent  of  twenty-eight  fatal  doses.  Again,  according 
to  Stille  (  Therapeutics,  ii.),  Brocklesby  habitually  prescribed  one  ounce  of  the  salt  a  day. 
and  Martin-Solon  even  two  ounces  per  diem. 

f  Case,  Pharmaceut.  Journ.,  Feb.  1846,  356. 


DIURETICS.  695 

In  the  treatment  of  poisoning  by  saltpetre,  after  the  stomach  and 
bowels  have  been  emptied,  the  usual  means  for  the  relief  of  toxic  gastro- 
enteritis should  be  resorted  to. 

POTASSII  CHLORAS.  U.  S. — Potassium  Chlorate  occurs  in  white  rhom- 
boidal  plates  of  a  pearly  lustre  and  of  an  acerb  taste,  soluble  in  seventeen 
parts  of  water  at  59°  F. ,  and  in  two  parts  of  boiling  water. 

PHYSIOLOGICAL  ACTION. — Locally,  this  salt  is  a  very  active  stimu- 
lant and  irritant.  As  a  poison  it  has  frequently  caused  death.*  The 
smallest  fatal  dose  is  not  known,  but  half  an  ounce  has  killed.  A  drachm 
taken  during  a  night  has  killed  an  infant  a  year  old,  and  three  drachms  a 
child  three  to  four  years  old.  The  symptoms  may  be  acute  or  subacute. 
In  the  rapid  cases  there  have  been  violent  vomiting,  profuse  diarrhoea, 
•excessive  dyspnoea,  great  failure  of  the  heart's  action,  and  marked  cya- 
nosis. In  the  subacute  cases  the  gastro-intestinal  symptoms  have  been 
severe,  with  generally  vomiting  of  blackish-green  matters  and  distinct 
swelling  of  the  liver  and  the  spleen.  The  urine  is  markedly  lessened  in 
quantity,  albuminous,  often  of  an  opaque  reddish-brown  or  blackish  color, 
and  showing  under  the  microscope  brownish  or  yellowish-brown  tube-casts, 
frequently  containing  the  detritus  of  blood-corpuscles.  Haemoglobinuria 
has  been  noticed, f  and  methsemoglobin  is  a  common  constituent.  The 
nervous  symptoms  have  been  severe  delirium,  coma,  tonic  and  clonic 
cramps,  and  a  peculiar  stiffness  of  the  extremities. 

Headache,  loss  of  appetite,  violent  pains  in  the  abdomen  and  other 
portions  of  the  body,  and  marked  abdominal  tenderness  have  usually 
preceded  the  loss  of  consciousness.  Not  rarely  there  are  minute  ec- 
chymoses  upon  the  surface  of  the  body,  and  even  more  frequently 
there  is  a  general  jaundice.  In  some  cases  the  patient  has  rallied  and 
seemed  to  be  on  the  road  to  recovery  when  the  fatal  relapse  has  oc- 
curred. 

After  death  the  blood  is  usually  chocolate-colored,  the  gastro-intes- 
tinal tract  is  inflamed,  the  liver  and  spleen  are  enlarged  and  filled  with 
the  brownish  debris  of  red  blood-corpuscles,  the  bone-marrow  and  the 
brain  are  often  similarly  colored,  while  the  mucous  membranes  are 
usually  swollen  and  ecchymosed.  The  kidneys  are  profoundly  affected, 
their  tubules  full  of  brownish  casts  and  their  epithelial  structure  evincing 
a  nephritis.  The  most  characteristic  and  probably  the  most  important 
of  the  lesions  is  the  change  in  the  blood,  which  was  first  noticed  after 
death  by  F.  Marchand."  L.  Riess88  noted  in  a  case  during  life  that 
many  of  the  red  blood-corpuscles  were  decolorized,  and  others  contained 
little  granules  of  an  elliptic  shape.  The  changes  in  the  blood  are  the 
result  of  the  formation  of  a  substance  apparently  identical  with  the 

*  For  collection  of  cases,  see  Chlorsaure  A'ali,  J.  von  Mering,  Berlin,  1885.  To  Jacobi, 
of  New  York,  belongs  the  credit  of  having  first  called  attention  to  the  dangerous  action 
of  this  much-abused  remedy  (Amer.  Med.  Times,  April,  1861,  245). 

t  Trans.  Internal.  Congress,  1881,  1.  463. 


696  LOCAL   REMEDIES. 

methsemoglobin  of  Hoppe-Seyler  and  characterized  by  the  appearance 
in  its  spectrum  of  a  dark  line  in  the  red.  Methaemoglobin  is  readily 
produced  by  mixing  either  sodium  chlorate  or  potassium  chlorate  with 
blood:  that  it  is  produced  in  the  body  during  life  has  been  experimen- 
tally proved  in  cats,  dogs,  and  rabbits  by  A.  Falck,89  by  H.  Lenhartz,*0 
and  by  Cahn,41  and  is  also  shown  in  man  by  the  wide-spread  staining  not 
only  of  the  interior  of  the  blood-vessels,  but  also  of  the  walls  of  the 
whole  lymphatic  system,  found  after  death  from  the  chlorate.  (Case, 
N.  Hammer.42) 

The  physiological  action  of  potassium  chlorate  is  evidently  not  domi- 
nated by  the  base  of  the  salt.  S.  J.  Meltzer  **  found  that  the  injection  of 
three  to  four  minims  of  its  five  per  cent,  solution  produced  immediate 
violent  convulsive  disturbances,  with  coma,  and  that  similar  symptoms 
were  caused  by  the  sodium  chlorate,  and  it  is  evident  that  both  salts  act 
directly  upon  the  nerve-cells. 

The  theory  that  potassium  chlorate  yields  its  oxygen  in  the  system  is 
absurdly  untrue.*  The  potassium  chlorate  escapes  unchanged  with  the 
saliva,  urine,  and  probably  all  the  secretions  of  the  body. 

Isambert  found  it  in  the  tears,  the  bile,  the  nasal  mucus,  and  even  in  the  milk 
of  nursing  women.  Rabuteau  took  five  grammes  of  the  salt,  and  recovered  from 
the  urine  4.873  grammes.  Isambert,  in  two  experiments,  recovered  respectively 
ninety-five  and  ninety-nine  per  cent,  of  the  ingested  potassium  chlorate  from  the 
urine.  J.  von  Mering,*3  out  of  fifteen  grammes  given  to  a  dog,  obtained  14.7 
grammes  ;  out  of  five  grammes  which  he  took  himself,  he  recovered  4.62  grammes  ; 
and  when  he  took  but  a  single  gramme  he  obtained  from  the  urine  of  the  next  ten 
hours  0.91  gramme.  From  the  saliva  and  urine  of  a  case  of  mercurial  stomatitis 
in  which  five  grammes  had  been  exhibited  he  recovered  4. 54  grammes.  Indeed, 
Marchand,  in  experiments  upon  the  lower  animals,  asserts  that  he  has  recovered  all 
of  the  ingested  chlorate  from  the  secretions,  and  we  must  conclude  that  it  practically 
all  escapes  from  the  body  unchanged.  F.  von  Mering  believes  that  some  of  the 
potassium  chlorate  is  reduced  in  the  system,  chiefly  because  he  thinks  that  methae- 
moglobin  is  formed  by  a  process  of  oxygenation.  The  exact  nature  of  methaemo- 
globin  is,  however,  not  made  out :  according  to  C.  A.  Macmunn,44  methaemoglobin 
is  probably  a  mixture  of  haematin  with  soluble  albumin,  Hoppe-Seyler  having 
shown  that  it  is  not  a  result  of  oxidation. 

Von  Mering  in  one  or  two  instances  in  the  dog  found  a  slight  in- 
crease in  the  chlorides  of  the  urine  during  the  administration  of  the 
chlorate,  and  it  is  possible  that  a  minute  quantity  of  the  chlorate  does 
undergo  deoxidation  ;  but  it  must  be  considered  established  that  any  such 
change,  if  it  occurs  at  all,  affects  so  small  a  portion  of  the  drug  as  not 
to  be  worthy  of  consideration. 

The  therapeutic  dose  of  potassium  chlorate  produces  no  sensible 
effects  in  the  system.  Isambert  found  that,  when  taken  by  himself  in 
doses  of  from  two  to  five  drachms,  it  caused  salivation,  free  diuresis, 
increase  of  the  appetite,  and,  when  not  well  diluted,  gastric  irritation  ; 

*  For  detailed  discussion,  see  tenth  edition. 


DIURETICS.  697 

the  urine  continued  strongly  acid,  and  contained  an  excess  of  rosacic 
acid,  uric  acid,  and  the  urates. 

THERAPEUTICS. — Largely  on  account  of  the  groundless  belief  that  it 
favors  oxidation  of  the  blood,  the  profession  has  in  the  past  used  potassium 
chlorate  in  many  forms  of  disease  believed  to  be  due  to  blood-poisoning. 
There  is,  however,  no  scientific  or  clinical  reason  for  believing  that  the  drug 
has  any  value  whatsoever  in  these  or  other  diseases,  except  through  its 
local  action,  and  without  doubt  its  free  use  in  diphtheria  has  often  greatly 
aided  in  the  production  of  a  fatal  result,  its  irritant  action  upon  the 
kidneys  making  it  a  dangerous  remedy  in  that  disease.  On  the  other 
hand,  it  is  a  very  valuable  local  remedy,  especially  in  diseases  of  the 
mucous  membrane  of  the  mouth.  In  the  follicular  or  aphthous  stoma- 
titis of  children  *  it  is  almost  a  specific,  its  free  elimination  with  the  saliva 
causing  it  to  be  constantly  present  in  the  mouth,  even  when  taken  inter- 
mittently. Its  local  influence,  however,  is  too  feeble  to  be  effective  in 
such  serious  diseases  as  diphtheria.  In  ordinary  sore  throat  or  angina 
the  combination  of  it  with  the  fluid  extract  of  sumach-berries  is  as  a 
gargle  most  effective. 

In  chronic  dysentery  and  other  diseases  of  the  colon  it  may  be  applied 
by  means  of  the  large  enemata.  In  hemorrhoids  the  injection,  when  the 
patient  goes  to  bed,  of  half  to  one  ounce  of  its  saturated  solution,  com- 
bined with  a  few  drops  of  laudanum  to  secure  retention,  is  often  of  the 
utmost  service.  In  stomatitis  and  allied  diseases  powders  of  potassium 
chlorate,  ten  to  fifteen  grains  (0.6-1  Gm. )  each,  should  be  put  dry  in 
the  mouth  every  three  to  six  hours,  so  as  to  secure  the  maximum  of  local 
action. 

LITHIUM. — When  one  of  the  official  salts  of  lithium  is  ingested  ab- 
sorption begins  almost  immediately.  The  lithium  has  been  detected  in 
the  urine  by  Clarence  Good  "  ten  minutes  after  the  hypodermic  injection. 
Excretion  goes  on,  however,  slowly,  since  the  same  chemist  has  found 
lithium  in  the  urine  twenty-three  days  after  the  injections  had  been 
stopped.  The  chief  channel  of  escape  is  through  the  urine,  but  excre- 
tion occurs  also  from  the  salivary  and  gastro-intestinal  glands.  No  cases 
of  serious  poisoning  by  a  lithium  salt  have  been  recorded,  but  we  have 
seen  large,  repeated  doses  produce  pronounced  malaise,  with  muscular 
weakness  and  some  disorder  of  the  digestion.  According  to  P.  Pergami  10° 
the  exhibition  of  lithium  carbonate  distinctly  increases  the  alkalinity  of 
the  blood. 

According  to  the  studies  of  Binet,45  the  lithium  salts  produce  in  mam- 
mals pronounced  feebleness,  with  nausea,  diarrhoea,  and  other  digestive 
disturbance,  increasing  dyspnoea,  fall  of  temperature,  and  death,  usually 

*  Laborde  (Bull.  Theraf).,  1874,  Ixxxvii.)  and  Tacke  (Inaug.  Diss.,  Bonn,  1878) 
have  shown  that  sodium  chlorate  acts  physiologically  like  the  potassium  salt ;  and  S. 
Ringer  and  H.  Sainsbury  (London  Lancet,  1882,  ii.  736)  have  found  it  equally  efficient 
in  stomatitis. 


698  LOCAL   REMEDIES. 

preceded  by  convulsions.  Death  is  said  to  be  due  to  a  direct  centric 
arrest  of  respiration,  although  a  markedly  depressing  influence  is  exerted 
upon  the  heart,  which  is  finally  arrested  in  diastole.  When  life  is  main- 
tained by  artificial  respiration  the  peripheral  nerves  become  entirely  para- 
lyzed and  the  muscles  affected,  as  is  shown  by  peculiar  fibrillary  contrac- 
tions. In  poisoned  frogs,  also,  the  excitability  of  the  muscles  is  some- 
what diminished. 

Lithium  salts  were  originally  recommended  by  Ure  and  Garrod  in  the 
treatment  of  uric  acid  diathesis  and  of  chronic  gout ;  theoretically  because 
it  was  believed  they  had  the  power  of  dissolving  uric  acid  and  the  urates. 
This  has  recently  been  denied  (Clarence  Good),  nor  has  it  ever  been 
proven  that  these  salts  are  distinctly  depurative,  increasing  the  elimi- 
nation of  effete  materials  through  the  kidneys.  That  they  have  such 
action  is,  however,  indicated  by  the  results  of  their  clinical  use,  and 
whilst  they  are  not  as  valuable  in  gout  as  was  originally  claimed  for 
them,  as  a  minor  remedy  they  are  often  serviceable  in  chronic  cases  in 
doses  of  from  five  to  fifteen  grains  (0.3-1  Gm. ),  given  after  meals.  E. 
Duche46  affirms  that  their  prolonged  local  application  is  very  useful  in 
relieving  gouty  joints^  and  that  in  gouty  conjunctivitis  frequent  washing 
of  the  eye  with  a  solution  of  lithium  carbonate,  i  to  500,  is  effective.* 

The  U.  S.  Pharmacopoeia  recognizes  Lithium  Benzoate  (LiTHii 
BENZOAS,  U.  S. ),  a  white  powder,  soluble  in  four  parts  of  water; 
Lithium  Carbonate  (  LITHII  CARBONAS,  U.  S. ),  similar  in  appearance, 
but  sparingly  soluble  in  water,  five  to  fifteen  grains  (0.3-1  Gm. ); 
Lithium  Citrate  (LiTHii  CITRAS,  U.  S. ),  a  white  deliquescent  powder, 
soluble  in  two  parts  of  water,  ten  to  thirty  grains  (0.6—2  Gm. )  ;  also  the 
Effervescent  Lithium  Citrate  (LiTHii  CITRAS  EFFERVESCENS,  U.  S. ), 
a  white  powder,  each  one  hundred  grains  of  which  contains  five  grains 
of  lithium  citrate,  with  sodium  bicarbonate  and  citric  and  tartaric  acids  to 
produce  effervescence.  When  added  to  water  it  effervesces  freely  and 
affords  the  most  pleasant  means  at  our  command  of  exhibiting  an  alkaline 
salt  of  lithium.  The  Lithium  Bromide  (LiTHii  BROMIDUM,  U.  S. )  is 
used  simply  as  a  bromide. 

PIPERAZINUM. — Piperazidine,  or  Diethylendiamine,  occurs  in  small, 
glassy,  lustrous  tables,  or,  in  the  form  of  the  hydrochlorate,  in  silky, 
lustrous,  lanceolate  crystals.  It  has  been  used  as  a  solvent  for  uric 
acid,  one  part  of  which  with  one  part  of  piperazine  will  dissolve  in  fifty 
parts  of  water.  It  has  also  been  alleged  that  it  will  dissolve  the  albu- 
minous substances  which  form  an  important  part  of  uric  acid  calculi. 
Undoubtedly,  however,  it  will  not  dissolve  an  already  formed  calculus  in 

* Mariinea.il1  s  Solution, — Martineau  affirms  that  he  has  obtained  very  remarkable 
results  in  the  treatment  of  diabetes  mellitus  by  the  use  of  a  solution  of  lithium  carbonate 
and  sodium  arsenate.  In  gouty  diabetes  this  arsenical  solution  of  lithium  may  prove 
of  service :  from  five  to  ten  grains  of  lithium  carbonate  and  one-thirtieth  of  a  grain  of 
sodium  arsenate  may  be  given  three  times  a  day. 


DIURETICS.  699 

the  human  bladder,  though  it  may  sometimes  be  of  service  as  a  solvent 
in  uric  acid  gravel. 

Piperazine  is  rapidly  absorbed  and  eliminated  through  the  kidneys, 
producing  a  reddish-brown  urine.  Concerning  its  general  physiological 
action  there  is  very  little  knowledge.  The  therapeutic  dose  produces  in 
man  ordinarily  no  symptoms,  but  we  have  seen  muscular  weakness  and 
general  depression  follow  the  continuous  exhibition  of  large  doses. 
Whether  it  does  or  does  not  affect  the  general  nutrition  is  unknown. 
Vogt  asserts  that  it  checks  uric  acid  elimination.  Ebstein  and  Sprague 
have  found  that  it  has  no  effect  either  upon  the  excretion  of  urea  or  of 
uric  acid.  It  has  been  very  largely  used  in  gout,  but  has  failed  to  sustain 
its  first  reputation,  although  in  occasional  cases  it  apparently  exerts  a 
markedly  beneficial  influence  for  a  time.  It  causes  too  much  pain  to  be 
used  hypodermically  ;  fifteen  to  twenty  grains  (1-1.3  Gm. )  of  it  may  be 
administered  by  the  mouth,  during  the  day,  in  a  quart  of  plain  or  car- 
bonated water.  It  is  too  hygroscopic  and  too  easily  decomposed  to  be 
given  in  powder  or  in  watery  solution,  but  the  solution  of  one  part  in 
twenty  of  alcohol  and  eighty  of  water  is  said  to  be  fairly  permanent. 
Van  der  Klip  has  found  that  in  the  lower  animals,  in  sufficient  dose,  it 
produces  vomiting,  irregular  breathing,  general  muscular  weakness,  and 
relaxation  ;  that  it  decreases  the  oxidizing  power  of  oxyhaemoglobin  and 
the  coagulability  of  the  blood  ;  and  that  it  checks  the  action  of  peptonizing 
ferments.  * 

LYCETOL. — Dimethylpiperazine  Tartrate. — A  white  powder,  readily  soluble 
in  water,  with  an  acidulous  rather  pleasant  taste.  It  has  been  brought  forward  as 
a  substitute  for  piperazine,  over  which  it  is  asserted  that  it  has  the  advantage  of 
being  less  apt  to  cause  disturbances  of  digestion  when  given  in  large  dose.  It  has 
been  favorably  reported  upon  in  purulent  cystitis  as  well  as  in  various  forms  of 
uric  acid  diathesis.  Dose,  from  fifteen  to  thirty  grains  (0.9-1. 9  Gm.)  given  daily 
in  from  one  to  two  pints  of  water. 

HEXAMETHYLENAMINA.     U.  S. 

Urotropin. — Formin. — This  substance  occurs  in  rhomboidal,  very 
soluble  crystals,  odorless,  and  of  a  sweet,  bitterish  taste.  In  the  presence 
of  acid  it  breaks  up  into  formaldehyde  and  ammonia  at  the  temperature 
of  the  human  body. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Absorption  and  Elimina- 
tion.— Urotropin  is  distinctly  irritant.  It  is  absorbed  with  great  rapid- 
ity, having  been  detected  in  the  urine  ten  minutes  after  its  ingestion,  and 
is  eliminated  from  the  kidneys  in  great  part  unchanged,  although,  as  first 
stated  by  Loebisch,47  it  is  to  some  extent  decomposed  in  the  organism 
with  the  liberation  of  formaldehyde. 

*  H.  Hildebrandt  (Berlin.  Klin.  Wochen.,  1894)  having  found  that  piperazine,  even 
in  small  quantities,  checks  the  saccharifying  influence  of  haemic  and  other  hydrolytic 
ferments,  although  it  has  no  destroying  influence,  tried  the  drug  in  diabetes  produced  in 
dogs  by  phloridzin  with  pronounced  success ;  so  that  the  remedy  is  certainly  worthy  of 
trial  in  diabetes  mellitus. 


7oo  LOCAL    REMEDIES. 

Casper 48  injected  urotropin  under  the  skin  of  a  rabbit  and  found  formaldehyde 
in  the  blood,  and  also  was  able  in  some  cases  to  detect  formaldehyde  in  the  urine  of 
persons  taking  urotropin,  an  observation  which  has  been  confirmed  by  Suter,81  and 
by  Citron.51  In  a  number  of  cases,  however,  these  chemists  failed  to  detect 
formaldehyde  in  the  urine  after  the  ingestion  of  urotropin,  and  P.  J.  Cammidge8* 
could  not  get  it  at  all ;  so  that  it  is  evident  that  elimination  of  formaldehyde  after  the 
ingestion  of  urotropin  is  an  inconstant  phenomenon.  It  has  been  suggested  that 
urotropin  is  decomposed  by  the  acid  juices  of  the  stomach,  but  F.  Suter81  found 
that  when  he  put  formaldehyde  into  the  stomach  of  the  rabbit,  or  took  formalde- 
hyde himself  in  safe  dose,  it  was  impossible  to  detect  it  in  the  urine  ;  so  that  any 
formaldehyde  liberated  by  the  urotropin  in  the  stomach  would  in  all  probability 
either  be  distributed  in  the  system  or  thrown  off  in  some  other  form  than  formalde- 
hyde. 

It  has  been  shown  by  Suter  that  when  urotropin  is  mixed  outside  of  the  body 
with  acid  urine  it  undergoes  decomposition,  although  this  does  not  occur  when 
the  urine  is  alkaline.  It  is  therefore  probable  that  that  portion  of  ingested  uro- 
tropin which  is  decomposed  suffers  change  in  the  kidney  and  upper  urinary  pas- 
sages ;  a  conclusion  which  is  confirmed  by  an  observation  of  Casper,  that  when  the 
urine  of  a  person  who  has  taken  urotropin  is  allowed  to  stand  a  continuous  forma- 
tion of  formaldehyde  goes  on  in  it  for  days. 

The  bactericidal  influence  of  urotropin  in  the  urine  is  not  altogether  dependent 
upon  its  conversion  into  formaldehyde,  since  Cammidge82  has  shown  that  it  has 
itself  very  marked  bactericidal  powers. 

General  Effects. — The  ordinary  therapeutic  dose  of  urotropin  pro- 
duces no  general  symptoms,  and  we  know  of  no  cases  of  poisoning  by  it. 
In  the  dog  the  daily  dose  of  two  hundred  and  eighty  grains  is  said  to 
cause  no  other  disturbance  than  renal  irritation  (Nicolaier).  The  in- 
gestion of  one  hundred  and  twenty  grains  a  day  of  it  usually  causes  in 
man  burning  pain  in  the  bladder  and  urethra,  especially  after  urination, 
followed,  if  the  dose  be  continued,  by  the  appearance  of  albumin,  red 
blood-corpuscles,  and  abundant  renal  epithelium  in  the  urine.  P.  J. 
Cammidge  has  noted  after  the  free  exhibition  of  urotropin  general  formi- 
cation, especially  intense  at  night,  ending  in  a  few  days  in  a  diffuse  rash, 
suggesting  that  of  measles. 

THERAPEUTICS. — Urotropin  was  especially  brought  forward  by  Bar- 
det49  and  Laquers  as  a  solvent  for  uric  acid,  but,  according  to  the  ex- 
periments of  Arthur  Nicolaier,50  it  is  less  active  in  this  respect  than  is 
piperazine,  and  is  of  no  practical  value  for  the  solution  of  renal  calculi. 
On  the  other  hand,  it  ranks  with  piperazine  as  useful  in  uric  acid  diathe- 
sis, and  is  especially  valuable  as  an  alterative  diuretic  in  the  treatment 
of  Pyelitis,  cystitis,  and  ammoniacal  phosphaturia.  In  gonorrhoea  it  has 
failed  to  be  of  service. 

Our  present  experimental  knowledge  so  strongly  confirms  the  clinical 
experience  of  Citron  that  in  order  to  get  the  good  effects  of  urotropin  in 
genito- urinary  inflammations  it  is  essential  to  maintain  the  acidity  of  the 
urine,  that  in  most  cases  benzoic  or  boric  acid  should  be  exhibited  at  the 


DIURETICS.  701 

same  time  as  is  urotropin.*  Urotropin  has  been  used  as  prophylactic 
against  nephritis  in  scarlet-fever.  Preisisch10*  found  9  per  cent,  of  kid- 
ney lesions  with  urotropin  as  against  13  per  cent,  without.  Dose,  fif- 
teen to  twenty  grains  (1-1.3  Gm. )  three  or  four  times  a  day,  well  diluted. 

QUINIC  ACID. — Acidum  Quinicum. — Chinic  Acid. — This  is  a  white  crystalline 
powder,  soluble  in  water,  which  was  originally  suggested  for  use  in  the  uric  acid 
diathesis  by  Weiss,88  who  claimed  that  it  markedly  reduces  the  formation  of  uric 
acid.  In  the  experiments  of  Ulrici,87  however,  quinic  was  found  to  have  no  distinct 
influence  upon  uric  acid  elimination,  and  Dolff  is  said  to  have  reached  similar  con- 
clusions. Nevertheless,  in  gouty  conditions  quinic  acid  has  been  used  to  a  consider- 
able extent,  especially  in  combination  with  antilithic  bases.  Of  these  combinations 
the  most  important  are  as  follows  : 

PIPERAZIN^E  QUINAS. — Sidonal. — A  white  powder,  freely  soluble  in  water, 
which  has  been  employed  in  chronic  gout  and  in  other  forms  of  uric  acid  diathesis. 
Richter  w  found  that  it  was  possible  to  prevent  in  pigeons  the  deposition  of  uric  acid 
in  the  joints,  which  normally  is  produced  by  injecting  potassium  chromate,  by  a 
simultaneous  use  of  sidonal.  The  dose  of  sidonal  is  seventy-five  to  one  hundred 
grains  (5-8  Gm. )  given  in  the  course  of  the  day,  dissolved  in  a  pint  or  more  of 
water. 

UROTROPIN.*:  QUINAS. — Quinotropine. — This  is  sold  in  two  forms :  Quino- 
tropine  I.,  containing  seventy-three  percent,  of  quinic  acid  and  twenty-seven  per 
cent,  of  urotropine  ;  and  Quinotropine  II.,  containing  eighty  per  cent,  of  quinic 
acid  and  twenty  per  cent,  of  urotropin.  Both  of  these  compounds  are  freely  soluble 
in  water,  yielding  with  sugar  a  lemonade-like  drink.  Nicolaier  and  Hagenberg90 
were  not  able  to  observe  any  diminution  in  the  excretion  of  uric  acid  in  human 
subjects,  produced  by  the  administration  of  quinotropine.  It  is  claimed  for  quinotro- 
pine  that  it  yields  formaldehyde,  and  is  useful  not  only  for  the  relief  of  t"he  uric  acid 
diathesis,  but  as  a  urinary  antiseptic.  Quinotropine  I.  is  given  in  doses  of  from 
fifty-five  to  eighty-two  grains  (3.7-5.5  Gm.)  per  day;  Quinotropine  II.,  seventy- 
five  to  one  hundred  and  twelve  grains  (5-7.5  Gm. )  per  day  ;  dissolved  in  one  to 
two  pints  of  water. 

HELMITOL. — This  is  a  urotropine  compound  which  is  said  by  Paul  Rosenthal 1(>l 
to  give  off  formaldehyde  in  much  larger  amounts  to  the  urine  than  does  urotropine, 
and  to  be  a  valuable  drug  in  the  treatment  of  inflammations  in  the  genito-urinary 
tract,  when  administered  in  doses  of  fifteen  to  twenty-three  grains  ( 1-1.5  Gm. )  three 
or  four  times  a  day. 

HETRALIN. — This  is  said  to  contain  sixty  per  cent,  of  hexamethylentetramin, 
and  is  soluble  in  one  to  four  parts  of  hot  water.  It  is  highly  recommended  by 
Ledermann  ^  in  specific  inflammations  of  the  genitalia,  administered  in  the  daily 
dose  of  one  and  a  half  to  two  grammes  in  three  to  five  portions. 

*  The  clinical  experiments  of  Suter  seem  worthy  of  note.  He  found  after  fifteen 
grains  of  salol,  boric  acid,  or  benzoic  acid  were  exhibited  to  a  healthy  subject  at  bed- 
time, the  early  morning  urine  made  as  good  a  medium  for  the  growth  of  bacteria  as 
ordinary  urine ;  but  if  forty-five  grains  of  urotropin  or  of  salol  were  given  the  urine 
passed  was  very  inert  towards  bacteria  ;  one  to  two  days  being  required  for  the  growth 
of  bacteria  in  the  salol  urine,  four  days  in  the  urotropin  urine,  provided  the  urine  was 
acid.  Salol  acted  as  well  in  the  alkaline  urine. 


702  LOCAL   REMEDIES. 

URASOL. — Acetyl-methylene-disalicylic  Acid. — This  substance,  which  was  first 
made  by  S.  Lewis  Summers,  is  said  to  contain  seventy-five  per  cent,  of  salicylic 
acid,  sixteen  per  cent,  of  acetic  acid,  and  eight  per  cent,  of  formaldehyde,  and  is 
alleged  to  be  broken  up  in  the  system  with  the  liberation  of  formaldehyde.  It 
occurs  as  a  yellowish-white  powder,  insoluble  in  water,  and  is  asserted  to  be  non- 
irritating,  so  that  it  may  be  given  in  capsules.  It  has  been  used  as  an  antirheumatic 
and  analgesic,  but  chiefly  for  germicidal  influence  on  the  genito-urinary  tract,  as  in 
cystitis.  Dose,  ten  to  twenty  grains  (0.6-1.0  Gm. ). 

STRONTIUM. 

Although  the  contrary  had  been  stated  by  Thomson  in  1818,  by  Vul- 
pian  in  1885,  and  by  Gautier  in  1886,  the  strontium  salts  were  generally 
believed  to  be  violently  poisonous  until  in  1891  J.  V.  Laborde52  pointed 
out  that  this  reputation  was  due  to  the  fact  that  the  commercial  strontium 
salts  were  contaminated  with  the  violently  poisonous  barium  salts,  and 
further  affirmed  that  the  chemically  pure  strontium  salts  were  innocuous 
unless  in  very  large  doses. 

Absorption  and  Elimination. — Our  present  knowledge  indicates 
that  the  soluble  salts  of  strontium  are  precipitated  by  the  alkalies  and 
phosphates  of  the  intestines,  so  that  they  are  only  partially  absorbed; 
and  that  elimination  is  even  more  slow  than  absorption  ;  so  that  stron- 
tium has  a  tendency  to  accumulate  in  the  liver,  in  the  muscles,  and  espe- 
cially in  the  bones. 

Horatio  C.  Wood,  Jr.,53  (confirmed  by  H.  C.  Wood  and  John  P.  Arnold5*) 
determined  that  when  an  official  salt  is  administered  by  the  mouth  only  a  minute 
proportion  of  it  can  be  obtained  from  the  urine,  whilst  a  great  amount  is  readily 
obtainable  from  the  faeces.  It  was  further  found  that  when  it  has  been  given 
hypodermically  only  a  minute  proportion  of  strontium  escapes  with  the  urine. 
The  research  of  L.  R.  Mendel  and  H.  C.  Thacher97  indicates,  however,  that  more 
of  the  strontium  is  absorbed  than  would  seem  to  be  indicated  by  the  results  of  the 
earlier  investigators.  These  researches  confirmed  the  results  previously  obtained, 
but  showed  further  that  when  strontium  is  subcutaneously  or  intravenously  given, 
a  large  portion  of  it  can  be  obtained  from  the  faeces,  so  that  elimination  must  take 
place  in  the  alimentary  canal. 

These  later  results  do  not,  however,  disprove  the  theory  that  the  strontium 
salts,  given  by  the  mouth,  are  chiefly  precipitated  in  the  alimentary  canal  and 
largely  escape  from  the  rectum.  Wood  and  Arnold  found  that  when  a  solution  of 
strontium  salicylate  was  added  to  the  o.  i  per  cent,  solution  of  hydrochloric  acid 
practically  all  of  the  salicylic  acid  is  at  once  set  free ;  also,  that  when  strontium 
salicylate  is  given  to  man  the  urine  in  an  hour  contains  much  of  the  acid,  but  only 
a  trace  of  the  base.  As  the  o.  i  per  cent,  hydrochloric  acid  solution  is  considerably 
less  acid  than  is  normal  gastric  juice,  and  as  alkalies  and  soluble  phosphates  ac- 
tively precipitate  soluble  strontium  salts,  it  is  altogether  probable  that  the  stron- 
tium found  in  the  faeces  after  the  administration  of  the  drug  by  the  mouth  repre- 
sents not  only,  as  believed  by  Mendel  and  Thacher,  strontium  which  has  been 
absorbed,  but  also  even  more  largely  strontium  which  has  failed  of  absorption. 

It  would  appear  that  in  most  cases  the  strontium  in  a  medicinal  salt 
acts  chiefly  as  a  carrier,  and  there  is  reason  for  believing  that  the  precipi- 
tated strontium  is  a  feeble  antiseptic,  and  that  when  in  the  alimentary 


DIURETICS.  703 

canal  it  acts  favorably  upon  the  digestive  glands  and  muscles,  so  that  in 
the  case  of  the  official  salts,  strontium  bromide,  strontium  iodide,  and  the 
non-official  strontium  salicylate,  the  base  is  useful  as  a  carrier  which 
yields  the  substance  with  which  it  is  in  combination  to  absorption  and  at 
the  same  time  improves  digestion.  How  far  the  clinical  results  which 
have  been  obtained  from  the  use  of  the  strontium  lactate  are  due  to  the 
strontium  and  how  far  to  the  lactic  acid  is  at  present  uncertain.* 

PHYSIOLOGICAL  ACTION. — So  far  as  we  are  aware,  there  are  no  cases 
on  record  in  which  any  distinct  symptoms  have  been  produced  in  man 
by  the  strontium  salt  unless  the  substance  with  which  the  strontium  was 
combined  was  sufficiently  active  to  make  itself  manifest.  Binet  affirms 
that  the  continuous  use  in  the  lower  animals  of  excessive  doses  produces 
general  feebleness  with  increasing  dyspnoea,  cyanosis,  clonic  convulsions, 
and  death  from  asphyxia.  When  recovery  occurs  the  motor  power  gradu- 
ally returns,  with  stiffness,  ataxic  movements,  and  not  rarely  with  the 
assumption  of  bizarre  positions.  In  an  elaborate  series  of  experiments 
by  Horatio  C.  Wood  and  John  P.  Arnold  it  was  found  that  the  intra- 
venous injection  of  the  strontium  lactate  or  nitrate  will  produce  in  the 
lower  animals  a  marked  progressive  lessening  in  the  pulse-rate,  with  a 
notable  increase  in  the  arterial  pressure  ;  the  diastolic  pauses  becoming 
so  long  and  the  cardiac  beats  so  powerful  that  in  the  dog  the  pulse-waves 
may  extend  over  as  much  as  eighty  or  ninety  millimetres.  If  the  dose 
has  been  repeated,  or  if  it  has  been  sufficiently  large  in  the  beginning, 
the  pulse-waves  after  a  time  become  very  quick  and  the  arterial  pressure 
falls,  although  it  may  not  reach  the  normal ;  finally,  after  a  toxic  dose,  both 
pulse-rate  and  pressure  at  last  gradually  fall  to  zero.  It  was  found  that 
section  of  the  spinal  cord  high  up  does  not  prevent  the  rise  of  the  arterial 
pressure  produced  by  the  strontium  salt;  and  that,  therefore,  this  rise  must 
be  due  to  an  action  exercised  upon  the  heart  itself  or  the  blood-vessel 
walls. 

It  was  further  demonstrated  by  Wood  and  Arnold  that  the  strontium 
salts  increase  the  cardiac  energy  in  the  isolated  frog's  heart  and  also 
cause  contraction  of  the  blood-vessels  by  a  local  action  upon  their  walls  ; 
and  that,  therefore,  the  circulatory  phenomena  spoken  of  are  partly  the 
outcome  of  cardiac  stimulation  and  partly  caused  by  contraction  of 
the  vessels,  the  final  fall  of  the  arterial  pressure  being  due  to  the  stimu- 
lation passing  over  into  paralysis.  As  was  pointed  out  some  time  ago  by 

*  That  the  effect  of  strontium  is  often  subordinate  to  that  of  the  substances  with  which 
it  is  combined  is  abundantly  proved.  Thus,  in  the  experiments  of  Laborde  a  certain 
dose  of  strontium  bromide  caused  localized  anaesthesia  with  a  rapid  development  of  som- 
nolence deepening  into  stupor,  with  marked  lessening  of  reflexes ;  followed,  if  the  dose 
had  been  large  enough,  by  collapse,  coma,  and  complete  loss  of  reflex  activity ;  whilst 
a  similar  dose  of  strontium  chloride  produced  no  sensible  effect.  The  presence  of  stron- 
tium phosphate  in  bone-ash  is  affirmed  by  some  and  denied  by  other  chemists.  Accord- 
ing to  the  experiments  of  Max  Cremer,  the  feeding  of  strontium  phosphate  to  young 
hounds  has  no  influence  in  preventing  the  development  of  rickets  (Munchen.  Med. 
Wochen.,  1892). 


704  LOCAL   REMEDIES. 

Lauder  Brunton,  strontium  affects  directly  the  muscles;  and  it  was  found 
by  Wood  and  Arnold  that  the  extremely  minute  dose  of  strontium  at 
first  markedly  increases  the  height  of  the  muscle-curve  and  widens  out 
its  base  ;  so  that  the  drug  primarily  increases  muscular  power  and  pro- 
longs the  contraction  period  ;  later,  there  was  muscular  paralysis  under 
the  continuing  influence  of  the  poison.  Experiments  upon  the  frog's 
heart  showed  that  the  strontium  salt  has  exactly  this  influence  upon  the 
heart,  so  that  evidently  strontium  is  a  muscle-poison  which  first  stimu- 
lates and  afterwards  paralyzes  the  muscle-fibres,  acting  both  upon  the 
muscles  of  the  skeleton  and  upon  those  connected  with  circulation ;  its 
stimulating  effect  upon  the  circulation  being,  therefore,  the  result  of  a 
wide-spread  general  influence  of  the  drug  upon  the  muscle-fibres  both  of 
voluntary  and  involuntary  life.  It  is  probable,  though  not  proved,  that 
the  muscle-fibres  in  the  intestines  are  also  affected  by  the  strontium  salt. 

According  to  Binet,55  in  poisoning  by  strontium,  the  nerve-centres  are 
more  powerfully  affected  by  the  drug .  than  are  the  muscle-fibres  them- 
selves, death  occurring  in  the  frog  from  centric  respiratory  paralysis  ; 
the  peripheral  nerves  and  the  muscles,  although  depressed,  still  retaining 
after  death  some  functional  power. 

STRONTII  LACTAS. — Strontium  Lactate  occurs  as  a  white  granular  powder,  or 
in  crystalline  nodules.  It  is  odorless,  of  a  slightly  bitter  saline  taste,  permanent 
in  the  air,  and  soluble  in  about  four  parts  of  water  ;  also  soluble  in  alcohol.  Accord- 
ing to  Germain  Se"e,  Paul,  Dujardin-Beaumetz,  and  other  French  clinicians,  it  is  a 
valuable  remedy  in  the  treatment  of  chronic  Bright1 s  disease,  increasing  the  amount 
of  urine,  diminishing  or  arresting  the  excretion  of  albumin,  and  improving  the  gen- 
eral nutrition.  In  albuminuria  due  to  pulmonary  congestion  the  drug  is  said  to  be 
of  service,  and  it  is  further  affirmed  that  its  influence  for  good  is  especially  marked 
in  desquamative  nephritis  and  much  less  pronounced  in  interstitial  nephritis.  In 
many  cases  there  is  no  increase  in  the  flow  of  urine,  and  the  good  achieved  seems 
to  be  due  to  an  alterative  influence  upon  the  secreting  structure  of  the  kidney.  In 
our  own  experience  the  strontium  lactate  has  not  yielded  results  such  as  are  ascribed 
to  it  by  the  French  observers.  It  is,  however,  a  harmless  remedy,  whose  use  should 
not  prevent  the  administration  of  other  appropriate  drugs.  The  usual  dose  is  from 
twenty  to  thirty  grains  (1.3-2  Gm. ),  given  three  times  a  day  in  solution  ;  but  much 
larger  amounts  have  been  exhibited  without  producing  apparent  symptoms. 

ALTERATIVE   DIURETICS. 

BUCHU— BUCHU.     U.  S. 

The  leaves  of  Barosma  betulina  and  crenulata,  natives  of  Southern 
Africa.  These  leaves  are  an  inch  or  less  in  length,  from  three  to  five 
lines  broad,  of  various  forms,  but  always  notched  on  the  edges,  and 
having  a  strong,  rather  rank,  yet  somewhat  aromatic  odor,  and  a  warm, 
bitterish  taste.  They  owe  their  virtues,  which  they  yield  to  water  and  to 
alcohol,  to  a  volatile  oil  and  a  bitter  extractive. 

THERAPEUTICS. — Buchu  is  a  mild  stimulant  and  alterative  to  the 
mucous  membrane  of  the  genito-urinary  organs,  useful  in  subacute  and 


DIURETICS.  705 

chronic  cystitis,  chronic  pyelitis,  and  irritation  of  the  bladder.  Its  oil  is 
undoubtedly  absorbed,  and  is  eliminated  by  the  kidneys,  to  whose  secre- 
tion it  imparts  its  odor.  In  irritated  bladder,  when  the  urine  is  highly 
acid,  and  when  there  is  a  constant  desire  to  urinate,  with  but  little  relief 
from  micturition,  buchu,  in  combination  with  a  vegetable  salt  of  potash 
and  the  sweet  spirit  of  nitre,  often  gives  great  relief.  The  dose  of  the 
fluid  extract  (FLUIDEXTRACTUM  BUCHU,  U.  S. )  is  a  teaspoonful  (4  C.c. ), 
well  diluted,  from  four  to  six  times  a  day. 

PAREIRA.  U.  S. — Pareira  Brava  is  the  root  of  Chondodendron  to- 
mentosum,  a  climbing  plant  of  South  America.  There  appear  to  be  in 
the  root  one  or  more  alkaloids.*  Pareira  Brava  has  been  used  with 
asserted  advantage  in  cystitis,  in  irritable  bladder,  and  in  chronic  gonor- 
rhoea, and  appears  to  exert  a  stimulant  action  upon  the  mucous  mem- 
brane of  the  whole  genito-urinary  apparatus.  The  doses  of  the  infusion 
(one  ounce  to  one  pint)  and  of  the  fluid  extract  (FLUIDEXTRACTUM 
PAREIRA,  U.  S. )  are  respectively  a  wineglassful  (62  C.c.)  and  a  tea- 
spoonful  (4  C.c. ),  four  or  six  times  a  day. 

UVA  URSI.  U.  S. — Bearberry  is  the  leaves  of  Arctostaphylos  Uva 
Ursi,  a  low  evergreen  shrub,  indigenous  to  northern  maritime  Europe, 
and  also  to  our  northern  coasts  as  far  south  as  New  Jersey.  They  are 
from  half  an  inch  to  an  inch  in  length,  wedge-shaped,  thick,  coriaceous, 
with  a  smooth,  rounded  margin.  The  odor  is  hay-like,  the  taste  bitter- 
ish, astringent,  and  somewhat  sweetish.  Uva  ursi  contains  gallic  acid, 
besides  arbutin,  which  occurs  in  long  acicular  colorless  crystals,  freely 
soluble  in  water,  less  so  in  alcohol  and  in  ether,  and  is  resolved  by  the 
action  of  sulphuric  acid  into  glucose  and  hydrochinone. 

THERAPEUTICS. — Uva  ursi  is  capable  of  acting  as  a  weak  astringent, 
but  has  been  long  used  in  medicine  for  its  influence  upon  the  genito- 
urinary mucous  membrane,  and  at  present  is  employed  only  in  chronic 
Pyelitis,  cystitis,  and  other  affections  of  the  genito-urinary  mucous  mem- 
brane, when  a  slightly  stimulant  and  an  astringent  action  is  desired. 
Hughes  found  that  in  doses  of  one  grain  arbutin  is  a  powerful  diuretic. 
It  seems  to  be  free  from  poisonous  properties,  as  Jablonowski M  took  in 
forty-eight  hours  eighteen  grammes  of  it  without  discomfort.  It  produces 
a  discoloration  of  the  urine  varying  from  pale  greenish  to  dark  greenish 
brown,  the  color  deepening  upon  standing.  It  has  been  proved  by  the 
researches  of  Von  Mering,57  of  L.  Lewin,58  and  of  Steffen5'  that  the 
discoloration  of  the  urine  is  due  to  the  breaking  up  of  the  arbutin  in  the 
body  into  glucose  and  hydrochinone.  The  change  probably  occurs  in  the 
kidneys,  as  arbutin  is  free  from  toxic  properties,  while  Brieger  has  shown 
that  hydrochinone  is  poisonous,  producing  in  man  giddiness,  ringing  in 
the  ears,  lessening  in  the  force  and  frequency  of  the  pulse,  etc.  The 

*  See  U.  S.  Dispensatory,  isth  ed.,  1085. 
45 


7o6  LOCAL   REMEDIES. 

experiments  of  Lewin  indicate  that  arbutin  is  the  active  principle  of 
uva  ursi,  and  Forster60  has  shown  that  hydrochinone  *  is  a  powerful  dis- 
infectant and  antiferment.  It  is  stated  that  a  one  per  cent,  solution  will 
arrest  putrefaction  and  alcoholic  fermentation,  while  one-half  per  cent, 
is  sufficient  to  check  butyric  fermentation.  Concerning  the  therapeutic 
value  of  arbutin  there  has  been  much  discussion,  but  the  fact  that  it  has 
failed  to  come  into  general  use  indicates  that  it  has  little  practical  effect, 
and  that  H.  Laurentz K1  was  right  in  asserting  that  uva  ursi  is  of  value  in 
genito-urinary  diseases  chiefly  on  account  of  its  tannic  acid  and  of  the 
volatile  oil  which  it  contains.  Whatever  may  be  the  value  of  arbutin,  it 
is  evident  that  the  solid  extract  fully  represents  the  drug,  of  which  it  is 
about  four  times  the  strength.  It  may  be  given  in  drachm  (4  Gm. )  doses 
three  or  four  times  a  day.  The  dose  of  the  fluid  extract  (FLUIDEX- 
TRACTUM  UV^E  URSI,  U.  S. )  is  two  to  four  fluidrachms  (7-15  C.c. ),  three 
to  four  times  a  day. 

CHIMAPHILA.  U.  S. — Pipsissewa  is  the  dried  leaves  of  Chimaphila 
umbellata,  a  little  indigenous  perennial,  distinguished  from  its  inert  con- 
gener C.  maculata  by  the  uniform  glossy  green  of  its  leaves.  The  latter 
are  about  an  inch  and  a  half  long,  wedge-shaped,  notched,  pointed,  and 
coriaceous.  They  contain  tannic  acid,  bitter  extractive,  and,  according 
to  Samuel  Fairbank,  a  crystalline  principle,  Chimaphilin.  Pipsissewa  is 
nearly  equivalent  to  uva  ursi  in  its  therapeutic  value,  though  not  so  effec- 
tive. The  dose  of  the  fluid  extract  (FLUIDEXTRACTUM  CHIMAPHILA, 
U.  S. )  is  a  teaspoonful  (4  C.c.)  three  or  four  times  a  day. 

TRITICUM.  U.S.  Couch-grass. — The  rhizome  of  Agropyrum  repens, 
a  common  grass  of  Europe  and  the  United  States,  is  believed  by  many 
surgeons  to  have  a  sedative  influence  upon  the  genito-urinary  organs,  and 
has  been  considerably  used  in  irritable  bladder  and  cystitis.  A  decoction 

*  According  to  the  experiments  of  Brieger,  hydrochinone  produces  in  man  giddiness, 
ringing  in  the  ears,  and  lessening  in  the  force  and  frequency  of  the  pulse.  In  the  experi- 
ments of  P.  J.  Martin  (  Therap.  Gaz.,  1887, 289),  it  caused  in  the  frog  violent  convulsions, 
followed  by  paralysis  and  death  through  failure  of  the  respiration,  both  convulsions  and 
paralysis  being  the  result  of  a  direct  influence  upon  the  spinal  cord.  Small  doses  pro- 
duced in  the  mammal  increase  of  the  arterial  pressure,  which,  if  the  dose  were  sufficient, 
was  followed  by  a  depression.  When  the  vaso-motor  system  was  paralyzed  and  the  heart 
isolated  from  the  central  nervous  system,  the  effect  of  hydrochinone  on  arterial  pressure 
was  scarcely  perceptible  :  so  that  it  is  probable  that  it  chiefly  affects  the  vaso-motor  sys- 
tem. The  bodily  temperature  is  lowered  by  large  doses  of  hydrochinone.  According  to 
the  experiments  of  Martin,  this  is  mainly  due  to  an  increase  of  heat-dissipation,  and  is, 
therefore,  probably  the  result  of  a  vaso-motor  paralysis.  H.  G.  Beyer,  after  experimenting 
upon  the  frog  and  terrapin  (Anter.  Journ.  Med.  Sci.,  April,  1886),  came  to  the  conclusion 
that  hydrochinone  affects  both  the  heart  and  the  vessels  as  a  paralyzant,  lessening  the 
rate  of  the  heart  and  the  amount  of  work  done,  and  causing  dilatation  of  the  arterioles. 
Antaeff  has  found  that  if  two  per  cent,  of  hydrochinone  be  added  to  fresh  urine  the  latter 
will  remain  for  many  days  without  undergoing  alkaline  fermentation,  but  that  if  hydrochi- 
none be  added  to  a  solution  of  urea  a  rapid  decomposition  of  the  urea  occurs,  which  Antaeff 
believes  to  be  the  result  of  a  direct  chemical  action  of  hydrochinone  or  urea  ( Lancet, 
April,  1887). 


DIURETICS.  707 

of  it  may  be  taken  ad  libitum,  or  the  fluid  extract  (FLUIDEXTRACTUM 
TRITICI,  U.  S. )  may  be  given  in  doses  of  two  to  three  fluidrachms 
(8-12  C.c. )  in  a  tumblerful  of  water  every  three  hours. 

JUNIPERUS. — Juniper  is  the  fruit  of  the  common  juniper,  Juniperus 
communis,  of  Europe  and  this  country.  These  berries  are  round,  bluish 
bodies,  about  the  size  of  a  large  pea,  of  a  sweetish,  terebinthinate,  aro- 
matic taste.  They  owe  their  properties  to  a  volatile  oil  (OLEUM  JUNIP- 
ERI,  U.  S. ).  They  yield  to  boiling  water  and  to  alcohol.  Juniper  is 
gently  stimulant  and  cordial  to  the  stomach.  Upon  the  kidneys  the  oil 
exerts  a  decided  stimulant  action,  and  when  freely  given  is  capable  of 
irritating  the  renal  organs  above  the  secreting  point,  and  of  producing 
lessened  secretion,  strangury,  and  even  suppression  of  urine.  Juniper  is 
largely  used  as  an  adjuvant  to  cream  of  tartar  or  the  alkaline  diuretics. 
On  account  of  its  stimulant  local  influence  upon  the  alimentary  canal,  it 
renders  the  cream  of  tartar  far  more  acceptable  to  the  stomach,  and  at 
the  same  time  aids  its  diuretic  action.  Sometimes  juniper  is  employed 
for  its  stimulant  action  on  the  mucous  membrane  of  the  genito- urinary 
organs  in  chronic  pyelitis  and  in  chronic  catarrh  of  the  bladder.  In  the 
form  of  the  compound  spirit  (SpiRixus  JUNIPERI  COMPOSITUS,  U.  S.), 
or  its  equivalent,  gin,  juniper  is  often  useful  in  the  subacute  congestion  of 
the  kidneys  frequently  seen  in  old  persons,  and  characterized  by  aching  in 
the  loins  and  lessened  urinary  secretion  without  more  serious  symptoms. 
Dose,  two  to  four  fluidrachms  (7—15  C.c.).  The  infusion  is  made  by 
macerating  an  ounce  of  the  berries  in  a  pint  of  boiling  water  for  an  hour, 
the  whole  to  be  taken  in  divided  doses  during  twenty-four  hours.  The 
dose  of  the  oil  (OLEUM  JUNIPERI,  U.  S. )  is  from  five  to  fifteen  drops 
(0.3-1  C.c.)  ;  of  the  spirit  (SPIRITUS  JUNIPERI,  U.  S. ),  from  thirty  to 
sixty  minims  (2-4  C.c.). 

OLEUM  ERIGERONTIS.  U.  S. — Erigeron  Canadense,  or  Canada  Flea- 
bane,  contains  a  large  proportion  of  a  yellowish  volatile  oil  of  a  rather 
pleasant  odor  and  taste,  which  has  properties  resembling  those  of  tur- 
pentine, but  much  less  stimulating.  It  may  be  employed  in  affections 
of  the  genito-urinary  organs  and  in  passive  hemorrhages.  It  is  especially 
valuable  in  menorrhagia.  According  to  Starke,6*  it  is  very  efficacious  in 
gonorrhoea.  The  dose  is  five  to  twenty  drops  (0.3-1.2  C.c.)  every  two 
or  three  hours,  and  is  best  administered  on  sugar. 

OLEUM  SANTALI,  U.  S. ,  is  a  pale  yellowish,  strongly  aromatic  vola- 
tile oil,  of  a  pungent,  spicy  taste,  from  the  distillation  of  the  wood  of 
Santalum  album.  It  is  insoluble  in  water,  but  readily  soluble  in  alcohol. 
When  pure,  it  is  a  local  irritant  and  probably  capable  of  affecting  the 
general  system,  although  its  physiological  action  has  not  been  properly 
investigated.  S.  Rosenberg w  has  noticed  after  doses  of  sixty  drops  a 
day  irritation  of  the  alimentary  canal,  burning  in  the  urethra  during 


7o8  LOCAL   REMEDIES. 

urination,  and  an  eruption  of  small  red  prominences  upon  the  entire 
surface  of  the  body,  involving  even  the  conjunctiva.  Oil  of  sandal-wood 
is  very  efficient  in  chronic  bronchitis  and  in  the  advanced  stages  of  acute 
bronchitis,  also  in  gonorrhoea  after  the  first  period  of  acute  inflammation. 
From  ten  to  twenty  minims  (0.6-1.2  C.c. )  of  it  may  be  given,  in  capsule 
or  emulsion,  three  or  four  times  a  day. 


TEREBINTHINA— TURPENTINE.     U.  S. 

Canada  Turpentine  (TEREBINTHINA  CANADENSIS,  U.  S),  or  Canada 
Balsam,  is  the  product  of  Abies  balsamea,  or  Balm  of  Gilead,  or  Ameri- 
can Silver  Fir,  as  it  is  variously  named,  a  beautiful  evergreen  indigenous 
to  the  extreme  Northern  United  States  and  to  the  British  provinces.  It 
is  a  thick  and  viscid  but  clear,  yellowish  liquid,  which  by  age  and  ex- 
posure becomes  converted  into  a  hard,  brittle,  translucent,  resinous  mass. 
Canada  Balsam  is  very  rarely,  if  ever,  used  in  medicine,  but  resembles 
turpentine  in  its  action  on  the  system  :  when  fresh  it  contains  about 
twenty  per  cent,  of  the  volatile  oil,  which  is  its  active  ingredient. 

White  Turpentine  (TEREBINTHINA — TURPENTINE,  U.  S. )  is  the  con- 
crete oleoresin  obtained  by  incising  Pinus  palustris  and  other  species 
of  pine.  The  supply  in  the  American  market  comes  almost  exclusively 
from  North  Carolina  and  other  of  our  Southern  States.  It  is  rarely,  if 
ever,  itself  used  in  medicine,  but  by  distillation  is  separated  into  a  vola- 
tile oil  and  a  resin  (Rositi),  which  is  official  under  the  name  of  RESINA. 
EMPLASTRUM  RESINS,  U.  S. ,  Adhesive  Plaster,  or,  in  ordinary  language, 
Sticking  Plaster,  is  formed  by  adding  rosin  to  lead  plaster.  CERATUM 
RESINS,  U.  S. ,  Resin  Cerate,  or  Basilicon  Ointment,  contains  rosin, 
yellow  wax,  and  lard  ;  it  is  used  as  a  mildly  stimulating  application  to 
indolent  burns,  ulcers,  etc.  CERATUM  RESIN^E  COMPOSITUS,  U.  S.,  con- 
tains also  turpentine  (11.5  per  cent. )  and  linseed  oil. 


OLEUM    TEREBINTHINA— OIL   OF    TURPENTINE.     U.S. 

This  is  a  yellowish,  highly  inflammable  oil,  of  a  strong  peculiar  odor 
and  a  hot  biting  taste,  moderately  soluble  in  alcohol,  freely  so  in  ether, 
very  slightly  so  in  water.  By  heating  with  muriatic  acid  it  is  converted 
into  a  red  liquid  and  a  white  crystalline  substance,  which,  from  its  re- 
semblance to  camphor,  has  received  the  name  of  artificial  camphor. 
Turpentine  is  remarkable  for  having  the  property  of  absorbing  oxygen 
and  converting  it  into  ozone.* 

PHYSIOLOGICAL  ACTION. — Turpentine  is  a  powerful  irritant,  causing 
in  a  very  short  time  inflammation  in  any  tissue  with  which  it  comes  in 
contact. 

*  For  a  study  of  the  effect  of  the  ozonizing  turpentine  oils,  see  Pal  lop  (Dorpat 
Thesis,  1889). 


DIURETICS.  709 

When  taken  by  a  healthy  person  in  moderate  doses,  it  produces  a 
sense  of  warmth  in  the  stomach,  soon  followed  by  exhilaration,  and,  if 
the  amount  be  sufficient,  giddiness  and  even  a  species  of  intoxication. 
The  pulse  is  increased  in  force  and  frequency.  The  turpentine  escapes 
from  the  body  through  the  lungs  and  kidneys,  imparting  its  own  odor 
to  the  breath  and  that  of  violets  to  the  urine.  Although  several  re- 
corded instances  prove  that  turpentine  is  capable  of  producing  death, 
cases  of  serious  poisoning  by  it  are  rare,  and  a  lethal  result  is  exceed- 
ingly so.  The  symptoms  noted  in  poisoning  by  it  are  most  of  them 
constant,  but  vomiting  and  purging  are  present  in  some  cases  and  not 
in  others.  Unconsciousness  is  generally  complete,  and  occasionally  is 
accompanied  by  dilated  pupils  ;  the  urine  is  very  much  lessened  in 
quantity,  often  bloody,  not  rarely  suppressed  ;  the  skin  is  sometimes 
dry,  sometimes  moist  ;  the  pulse  is  feeble,  rapid,  and  generally  regular. 

The  lethal  dose  must  be  very  large,  but  it  is  not  definitely  known, 
since  recovery  from  four  ounces  in  an  infant  fourteen  months  old  has 
been  reported.  In  Maund's65  case,  death  was  supposed  to  have  been 
produced  in  an  intemperate  woman  by  six  ounces;  and  Philip  Miall" 
has  recorded  an  instance  of  death  caused  in  an  infant  fourteen  weeks 
old  by  turpentine,  of  which  half  an  ounce  was  thought  to  have  been 
taken. 

Our  knowledge  of  the  action  of  turpentine  upon  the  circulation  is 
very  imperfect  :  the  results  which  have  been  obtained  by  experimenters 
are  so  diverse  as  to  indicate  that  different  varieties  of  the  oil  affect  the  cir- 
culation differently,  or  else  that  the  oil  alters  in  its  physiological  influence 
when  allowed  to  stand  and  absorb  ozone.  R.  Kobert,67  using  the  Euro- 
pean turpentine,  found  that  in  moderate  doses  it  exerted  a  powerful 
stimulating  influence  upon  the  inhibitory  reflex  centre,  and  also  elevated 
the  blood-pressure  by  stimulating  the  vaso-motor  centres.  Very  large 
doses  appeared  to  paralyze  both  of  the  centres  spoken  of,  causing  de- 
cided fall  in  the  arterial  pressure.  The  respiration  was  first  increased  in 
frequency,  but  later  very  much  diminished.  The  blood  became  very  dark, 
and  the  heart  was  finally  paralyzed.  The  vagi  and  depressor  nerves  did 
not  appear  to  be  affected,  nor  indeed  did  any  of  the  peripheral  nerves 
or  the  muscles.  It  is  said  that  these  results  are  in  accord  with  those 
previously  published  by  Azary  in  the  Hungarian  language,  and  Hoppe68 
concludes  as  the  result  of  his  own  experiments,  presumably  made  with 
European  oil  of  turpentine,  that  the  vaso-motor  nerves  are  very  early 
influenced  by  the  drug.  On  the  other  hand,  in  a  series  of  experiments 
made  in  the  laboratory  of  the  University  of  Pennsylvania  by  H.  A. 
Hare69  with  American  oil  of  turpentine,  it  was  found  impossible  to  raise 
the  arterial  pressure  for  more  than  two  or  three  minutes,  and  then  no 
more  than  ten  millimetres  of  mercury.  Large  doses  produced  a  pro- 
nounced fall  of  arterial  pressure,  with  great  cardiac  depression,  to  which, 
indeed,  Hare  attributes  the  fall  of  the  blood-pressure.  Doses  which  had 
no  effect  on  the  blood-pressure  increased  the  frequency  of  the  pulse  for 


yio  LOCAL   REMEDIES. 

a  length  of  time.  The  increase  of  the  pulse-rate  was  evidently  due  to 
an  action  upon  the  heart  itself,  for  it  occurred  when  the  turpentine  was 
applied  directly  to  the  heart  of  the  frog  as  well  as  in  the  dog  after  section 
of  the  accelerator  nerves  and  the  vagi.  When  large  doses  were  ad- 
ministered the  pulse  became  slow, — probably,  as  Hare  believes,  as  the 
result  of  stimulation  of  the  pneumogastric  nerves,  since  section  of  these 
nerves  was  followed  by  the  normal  rise  in  pulse-frequency.  Le"on  Crucis 70 
has  made  some  experiments  which  indicate  that  when  turpentine  is  given 
in  toxic  doses  to  rabbits  it  increases  the  coagulability  of  the  blood  and 
gives  rise  to  numerous  minute  hepatic  and  pulmonic  thrombi. 

F.  Fleischmann 7l  found  that  two  drops  produced  paralysis  in  the 
frog, — first  of  voluntary  and  afterwards  of  reflex  activity  ;  in  the  cat  and 
in  the  rabbit,  toxic  doses  abolished  reflex  activity,  but  caused  violent 
lethal  convulsions.  The  preservation  of  voluntary  movement  in  the  frog 
after  the  loss  of  reflex  activity,  which  has  been  confirmed  by  Hare, 
indicates  that  toxic  doses  of  turpentine  paralyze  the  sensory  nervous 
system,  either  in  the  cord  or  in  the  peripheral  nerves. 

The  irritant  action  of  turpentine  upon  the  kidneys  and  genito-urinary 
tract  is  very  decided.  When  moderate  doses  (ten  drops  every  three 
hours)  of  turpentine  are  taken,  there  are  usually  no  renal  symptoms 
produced,  except  a  slight  increase  of  the  urine.  Somewhat  larger 
amounts,  when  exhibited,  are  apt  to  give  rise  to  aching  in  the  loins  and 
to  frequent  micturition,  with  perhaps  urethral  pain  accompanying  the 
act.  If  still  larger  quantities  are  ingested,  these  symptoms  are  intensi- 
fied, and  at  the  same  time  the  secretion  of  urine  is  diminished.  After 
very  large  repeated  doses  of  the  drug,  the  aching  in  the  loins  is  very 
great,  often  with  spasmodic  pain  in  the  ureters  ;  a  constant  desire  to 
pass  water  struggles  with  the  inability  to  micturate,  caused  by  the 
urethral  spasm  ;  the  urine  is  very  scanty,  albuminous,  and  even  bloody  ; 
priapism  may  be  present,  and  an  intolerable  irritation  may  affect  all  the 
pelvic  organs. 

THERAPEUTICS. — Externally  the  oil  of  turpentine  is  very  much  em- 
ployed as  a  powerful  counter-irritant.  It  is  useful  more  especially  when 
it  is  desired  to  act  upon  a  large  extent  of  surface.  When  a  very  in- 
tense permanent  local  impression  is  required,  a  blister  is  to  be  preferred. 
Thus,  in  pleurisy  a  blister  may  be  used,  in  bronchitis  turpentine  stupes. 
In  preparing  the  latter  the  turpentine  should  first  be  warmed  by  setting 
the  vessel  containing  it  in  hot  water,  then  a  piece  of  flannel,  just  previ- 
ously saturated  with  hot  water  and  wrung  out  as  dry  as  possible,  should 
be  dipped  in  the  turpentine  and  again  wrung  out.  It  is  then  ready  for 
application,  and  may  be  left  on  from  fifteen  minutes  to  half  an  hour, 
according  to  the  sensitiveness  of  the  skin. 

Another  local  use  of  the  oil  of  turpentine  is  as  an  addition  to  ene- 
mata.  From  a  teaspoonful  to  a  tablespoonful  of  it  mixed  with  double  its 
amount  of  olive  oil  renders  opening  enemata  much  more  active,  espe- 
cially in  causing  the  expulsion  of  flatus.  Turpentine  enemata  contain- 


DIURETICS.  711 

ing  much  of  the  oil  in  a  small  bulk  are  also  constantly  used  with  good 
effect  in  arousing  the  system  from  stupor  arising  from  narcotic  poison  or 
similar  causes. 

In  ulcer ation  of  the  bowels  turpentine  taken  by  the  stomach  is  often 
very  efficient,  probably  acting  locally  in  the  intestine,  and  in  old  gastric 
ulcers  good  results  are  sometimes  derived  from  its  use.  In  a  single  large 
dose  (half  to  one  fluidounce,  with  an  equal  amount  of  castor  oil)  it  is  an 
efficient  vermifuge.  It  may  also  be  used  as  a  stimulant  in  low  fevers, 
particularly  when  the  tongue  is  dry  and  red. 

In  typhoid  or  enteric  fever  it  without  doubt  acts  as  a  local  stimulant 
to  the  ulcerated  bowel,  besides  influencing  the  general  condition  of  the 
system.  There  are  two  conditions  or  stages  in  the  diseases  named  in 
which  it  is  especially  useful, — indeed,  is  of  incalculable  service.  About 
the  end  of  the  second  week  the  tongue  sometimes  becomes  very  dry, 
red,  chapped,  perhaps  coated  in  the  centre  with  a  brownish  fur,  and  at 
the  same  time  marked  meteorism  develops.  Ten  drops  (0.6  C.c. )  of 
turpentine  every  two  hours  during  the  day  and  every  three  hours  during 
the  night  will  in  the  majority  of  cases  remove  the  bad  symptoms  noted. 
That  the  action  of  the  oil  is  largely  a  local  one  is  shown  not  only  by  the 
arguments  of  the  introducer  of  the  practice,  George  B.  Wood,  but  also 
by  the  value  of  the  same  treatment  when  diarrhoea  persists  after  the 
acute  stage  of  the  fever  has  passed.  When  convalescence  is  protracted, 
when  there  is  a  constant  tendency  to  the  recurrence  of  diarrhoea, — 
when,  in  other  words,  the  ulcers  of  Peyer's  patches  are  slow  to  heal, — 
turpentine  acts  almost  as  a  specific.  These  clinical  results  have  received 
scientific  confirmation  in  the  work  of  Theo.  Omelchenko,72  who  finds 
that  the  bacillus  of  typhoid  fever  will  not  develop  in  air  containing  diluted 
vapor  of  turpentine,  and  dies  when  the  atmosphere  is  saturated  with  the 
vapor.  Thymol  appears  to  be  even  more  active  than  is  turpentine. 

In  typhoid  bronchitis  and  pneumonia,  especially  as  intercurrent  in 
typhus  fever  and  similar  diseases,  turpentine  applied  externally  and  taken 
internally  is  often  very  useful.  The  same  may  be  said  of  the  low  forms 
of  piierperal fever.  In  this  disease  the  abdomen  should  be  kept  covered 
with  fomentations  of  the  oil  and  of  warm  water  alternately,  the  counter- 
irritant  being  used  as  constantly  as  a  proper  regard  for  the  skin  of  the 
patient  will  allow.  Internally  it  should  be  given  in  very  large  doses  (ten 
to  fifteen  minims  every  two  hours). 

In  hemorrhages  from  the  stomach,  bowels,  or  lungs  turpentine  has 
acquired  celebrity,  but  it  is  hardly  so  much  used  as  formerly.  It  is  in 
the  ataxic  cases  that  it  is  useful.  We  have  very  rarely  employed  it,  as 
the  oil  of  erigcron  has  seemed  even  more  efficacious,  and  is  much  more 
pleasant  to  the  patient.  In  purpnra  hamorrhagica  turpentine  has  been 
highly  praised. 

Oil  of  turpentine  is  never  employed  to  increase  the  flow  of  urine  for 
the  purpose  of  affecting  serous  effusions.  As  a  diuretic,  it  is  used  solely 
for  its  local  influence  upon  the  organs.  Excessive  diuresis  sometimes  is 


712 


LOCAL   REMEDIES. 


apparently  dependent  upon  a  relaxed  condition  of  the  kidneys,  and  under 
these  circumstances  oil  of  turpentine  may  be  of  service.  Chronic  pye- 
litis,  chronic  cystitis,  and  gleet  may  be  benefited  by  its  use. 

In  giving  turpentine  in  these  cases,  it  should  always  be  borne  in  mind 
that,  with  the  exception  of  cantharides,  it  is  the  most  actively  stimulating 
of  all  the  diuretics,  and  must  be  employed  only  when  such  a  remedy  is 
called  for.  In  those  comparatively  rare  cases  of  urinary  incontinence 
which  are  dependent  upon  debility  of  the  bladder,  turpentine  is  some- 
times of  great  service.  When  the  same  symptom  is  spasmodic,  the 
remedy,  of  course,  is  harmful.  In  absolutely  passive  htzniaturia,  in  im- 
potence, in  certain  conditions  of  spermatorrhoea,  and  in  amenorrhcea, 
when  great  local  debility  exists,  turpentine  may  be  tried  with  fair  hopes 
of  its  being  useful. 

ADMINISTRATION. — The  dose  of  turpentine  is  ten  to  fifteen  drops 
(0.6-0.9  C.c. )  in  emulsion,  given  from  four  to  six  times  a  day.  EMUL- 
SUM  OLEI  TEREBINTHIN.E,  U.  S. ,  contains  fifteen  per  cent,  of  oil  of 
turpentine  and  is  flavored  with  oil  of  bitter  almonds.  Dose,  one  drachm 
(4C.c.). 

It  has  been  asserted  that  oil  of  turpentine  is  a  powerful  bactericide; 
but  the  experiments  of  Koch  and  of  Christmas- Dirckinck-Holmfeld" 
appear  to  show  that  its  general  antiseptic  properties  are  feeble. 

COPAIBA— COPAIBA.      U.S. 

The  oleoresin  of  Copaiba  Langsdorffii  and  of  other  species  of  Co- 
paiba, large  trees  growing  in  Brazil.  Copaiba  is  a  yellowish  liquid,  of 
varying  viscidity  according  to  age,  of  a  strong,  terebinthinate,  peculiar 
odor,  and  a  bitter,  burning,  disagreeable  taste.  It  mixes  uniformly  with 
absolute  alcohol  and  volatile  and  fatty  oils,  and  is  readily  dissolved  by 
ether.  It  contains  a  volatile  oil,  a  small  quantity  of  soft,  viscid  resin, 
about  fifty  per  cent,  of  a  hard,  acid  resin,  and  a  peculiar  crystallizable 
acid,  copaivic  acid,  which,  according  to  Bernatzik,  is  unimportant,  the 
activity  of  the  drug  depending  upon  the  oleoresin. 

PHYSIOLOGICAL  ACTION. — The  local  action  of  copaiba  is  that  of  an 
active  stimulant  or  a  mild  irritant.  When  taken  internally,  it  yields  its 
active  principle  to  absorption  and  elimination  through  the  kidneys.  The 
elimination  takes  place  slowly,  as  Bernatzik 7i  found  the  oil  in  the  urine 
as  much  as  four  days  after  its  ingestion. 

Upon  the  general  system  copaiba  has  little  influence ;  eighteen 
grammes  of  its  volatile  oil,  taken  in  three  doses  during  twelve  hours, 
caused  only  a  slight  elevation  of  the  pulse-rate  and  of  the  temperature, 
with  later  vomiting  and  purging,  and  still  later  burning  in  the  urethra 
and  strangury  (Bernatzik).  In  susceptible  persons  the  evidences  of  the 
local  action  of  the  drug  are  more  marked,  it  causing  decided  symptoms 
of  gastro-intestinal  irritation,  accompanied  by  marked  fever  and  irrita- 
tion of  the  urinary  organs,  such  as  strangury,  and  even  almost  complete 
suppression.  In  Bernatzik' s  trials  fifteen  grammes  of  the  resin,  taken 


DIURETICS.  713 

within  five  hours,  produced  violent  purging  and  vomiting,  with  much 
abdominal  pain. 

The  discovery  in  1841  by  G.  O.  Rey,  that  the  addition  of  nitric  acid 
to  the  urine  of  persons  taking  copaiba  will  produce  a  precipitate  re- 
sembling that  of  albumin,  has  led  to  much  discussion.  To  obtain  this 
precipitate  the  copaiba  must  be  freely  given.  As  shown  by  Bernatzik, 
the  precipitate  probably  consists  of  the  oxidized  oil  united  to  some 
urinary  principles.  The  copaiba-red  of  Quincke  is  a  substance  found  in 
the  urine  of  persons  taking  the  oil  of  copaiba  ;  it  is  an  acid,  whose  salts 
have  the  property  of  reducing  the  oxide  of  copper  and  of  polarizing  to 
the  left,  and  may  be  a  source  of  error  in  the  diagnosis  of  diabetes. 
When  a  pure  copaiba  resin  is  used,  although  the  copaiba-red  cannot  be 
detected  in  the  urine,  the  urine  still  responds  to  Trommer's  test  for  sugar. 

As  a  stimulant  to  the  genito-urinary  mucous  membrane,  copaiba  is 
distinctly  more  active  than  buchu,  but  less  irritating  than  the  oil  of  tur- 
pentine. It  may  be  used  in  chronic  pyelitis  and  cystitis,  but  is  chiefly  em- 
ployed in  advanced  stages  of  gonorrhoea;  if  administered  during  the 
height  of  the  inflammation  in  these  diseases,  it  is  liable  to  aggravate  the 
symptoms.  It  is  also  capable  of  affecting  other  mucous  membranes  than 
that  of  the  genito-urinary  tract,  so  that  it  may  sometimes  be  given  with 
advantage  in  old  indolent  ulcers  of  the  stomach,  in  chronic  diarrhoea  and 
dysentery,  in  advanced  bronchitis,  and  especially  when  in  chronic  bron- 
chitis there  is  very  free  muco-purulent  expectoration.  As  a  local  appli- 
cation it  is  sometimes  very  advantageous  in  chronic  chilblains  and  other 
diseases  of  the  skin.  In  doses  of  forty-five  grains  (3  Gm.)  a  day  the 
resin  is  said  to  be  actively  hydragogue  and  effective  in  dropsies  which 
are  not  dependent  upon  renal  disease.  Dose  of  copaiba,  half  to  one 
fluidrachm  (2-4  C.c.),  in  capsules  ;  of  the  oil  (OLEUM  COPAIBA,  U.  S. ), 
which  is  isomeric  with  oil  of  turpentine,  eight  to  fifteen  minims  (0.5-1 
C.c. ),  in  capsules.  MASS  A  COPAIBA,  U.  S. ,  is  an  entirely  ineligible 
preparation. 

CUBEBA— CUBEB.     U.  S. 

The  unripe  fruit  of  Piper  cubeba,  a  climbing  plant  of  Java  and  other 
portions  of  the  East  Indies.  These  berries  are  blackish-veined,  about 
the  size  of  a  small  pea,  and  have  attached  to  them  a  short  stalk  three 
or  four  lines  long.  Their  odor  is  aromatic  and  peculiar  ;  their  taste 
warm,  camphoraceous,  and  peculiar.  They  contain  cubebic  acid,  cu- 
bebin,  volatile  oil,  and  resin,  and  are  fully  represented  by  the  official  oleo- 
resin.  Bernatzik75  has  found  that  cubebin  is  inert,  which  is  in  accord 
with  the  statement  of  Heffter,76  that  cubebin  passes  through  the  ali- 
mentary canal  without  absorption,  so  that  it  is  possible  to  recover  from 
the  faeces  almost  the  whole  amount  ingested. 

Cubeb  is  a  local  stimulant  which  has  very  little  effect  upon  the  gen- 
eral system.  In  large  doses  it  produces  a  gastric  and  genito-urinary  irri- 
tation proportionate  in  severity  to  the  amount  taken.  Like  copaiba,  it 


7i4  LOCAL   REMEDIES. 

occasionally  causes  an  urticaria,  which  is  probably  due  to  the  gastric 
irritation.  It  yields  to  absorption  and  elimination  its  active  principles, 
which  can  be  detected  in  the  urine  by  the  addition  of  nitric  acid,  when  a 
precipitate  resembling  that  of  albumin  occurs. 

In  Bernatzik's  experiments  ten  grammes  of  magnesium  cubebate  caused  slight 
acceleration  of  the  pulse  and  gastric  uneasiness,  with  increased  elimination  of  uric 
acid.  Half  an  ounce  of  the  oil,  taken  in  thirty-six  hours,  produced  very  decided 
gastric  irritation,  with  the  appearance  in  the  urine  of  the  oxidized  oil  in  the  form  of 
a  resin,  and  a  very  great  decrease  in  the  elimination  of  uric  acid.  After  fifty 
grammes  of  the  powdered  cubeb  the  gastro-mtestinal  irritation  was  most  pronounced 
and  the  nitric  acid  precipitate  in  the  urine  very  abundant. 

Cubeb  is  used  to  relieve  precisely  the  same  conditions  as  copaiba.  In 
many  cases  the  best  results  are  to  be  obtained  by  the  combined  employment 
of  the  two  remedies.  It  has  received  much  praise  as  an  internal  remedy 
in  chronic  hemorrhoids.  It  is  useful  as  a  local  stimulant  in  the  relaxation 
of  the  larynx  frequently  seen  in  public  speakers  following  slight  colds  and 
overuse  of  the  voice,  chewing  the  berries  often  bringing  relief  to  the 
throat  and  tone  to  the  voice.  The  powdered  drug  may  be  used  as  a 
snuff  in  coryza.  In  this  disease,  as  in  all  others,  cubeb  should  not  be 
employed  in  the  earlier  stages  before  secretion  has  been  established,  but 
later  in  the  affection  when  the  discharge  is  profuse. 

The  dose  of  the  powdered  cubeb  is  from  half  to  three  drachms  (2-11 
Gm.);  of  the  volatile  oil  (OLEUM  CuBEByE,  U.  S. ),  fifteen  drops  (i  C.c. ), 
given  in  capsules  and  gradually  increased  to  half  a  drachm,  unless  some 
effect  is  previously  produced  upon  the  urinary  organs  ;  of  the  fluid  ex- 
tract (EXTRACTUM  CUBEB^E  FLUIDUM,  U.  S. ),  ten  to  forty  minims 
(0.6-2.5  C.c. ).  The  best  preparation  is  the  oleoresin  (OLEORESINA 
CUBEB/E,  U.  S. ),  dose,  ten  to  fifteen  minims  (0.6-1  C.c.),  in  capsules. 

MATICO.  U.  S. — Matico,  the  dried  tops  of  the  Piper  angustifolium 
of  Peru,  contains  a  volatile  oil,  resin,  and,  it  is  said,  a  bitter  principle, 
maticin.  It  is  a  softish  mass  which  is  largely  employed  as  a  styptic,  and 
probably  acts  chiefly  mechanically,  coagulating  the  blood  in  its  inter- 
stices, adhering  to  the  wound,  and  thus  arresting  the  hemorrhage.  It 
has  also  been  employed  in  internal  hemorrhages  and  in  gonorrhcea.  In 
these  affections  it  probably  acts  similarly  to  oil  of  turpentine,  although 
much  less  of  a  stimulant  and  much  more  feeble.  The  fluid  extract 
(FLUIDEXTRACTUM  MATICO,  U.  S.)  and  the  tincture  (TINCTURA  MATICO 
— ten  per  cent. ,  U.  S. )  may  be  respectively  given  in  doses  of  forty-five 
minims  (3  C.c.)  and  two  fluidrachms  (7  C.c.). 

CANTHARIS. — Cantharides  is  considered  elsewhere  in  detail  (see 
EPISPASTICS),  and  it  is  only  necessary  here  to  say  a  few  words  in  regard 
to  its  use  in  diseases  of  the  genito-urinary  tract.  The  active  principle  of 
Spanish  flies  is  certainly  eliminated  by  the  kidneys,  and  acts  therefore 
locally  upon  these  organs,  as  well  as  upon  those  over  which  their  secre- 


DIURETICS.  715 

tion  flows.  The  influence  exerted  by  this  means  is  simply  one  of  intense 
irritation,  cantharides  being  an  irritant  to  these  organs  in  any  dose  suffi- 
ciently large  to  have  an  effect.  Indeed,  of  all  the  official  drugs  can- 
tharides is  the  most  actively  irritant  to  the  kidneys  and  their  subordinate 
organs.  Consequently  it  is  employed  only  when  an  intensely  stimulant 
action  is  desired,  as  in  obstinate  gleet,  in  which  affection  it  is  often  com- 
bined very  advantageously  with  the  tincture  of  ferric  chloride.  In  pyelitis 
and  cystitis  it  is  very  rarely  indicated,  but  may  be  cautiously  used  in  very 
chronic  cases.  The  tincture  of  cantharides  is  the  only  preparation  used  in- 
ternally. Dose,  one  to  five  minims.  Cantharides  has  been  strongly  recom- 
mended by  Beven. M  Other  clinicians  give  the  full  dose  in  ataxic  hamaturia. 

KAVA. — The  root  of  Piper  methysticum  is  used  in  the  Sandwich  Islands  as  the 
basis  of  an  intoxicating  liquor  known  as  kava-kava,  kawa,  or  ava.  It  contains  a 
crystalline  principle  analogous  to  piperin,  which  its  discoverer,  Gobley,  called 
meihysticin,  besides  an  acrid  resin,  kavin,  and  a  volatile  oil. 

L.  Lewin  "  finds  that  when  the  kava  resin  is  injected  into  the  frog  it  produces 
a  very  pronounced  loss  of  sensation  at  the  point  of  injection,  due  to  a  paralysis  of 
the  peripheral  endings  of  the  sensory  nerves,  and  that  after  the  absorption  of  the 
remedy  there  is  loss  of  voluntary  motion  and  reflex  activity,  which  is  chiefly  of 
spinal  origin.  In  experiments  made  upon  the  warm-blooded  animals  he  obtained 
similar  phenomena, — namely,  local  anaesthesia  at  the  point  of  injection,  followed, 
after  absorption,  by  general  paralysis,  due  to  a  direct  depression  of  the  motor  side 
of  the  spinal  cord,  the  motor  nerves  and  the  muscles  remaining  intact.  According 
to  Dario  Baldi,78  the  active  principle  of  kava  produces  in  the  dog  a  very  short 
period  of  excitement  of  the  sensory  nerves,  followed  by  a  complete  paralysis,  at  a 
time  when  the  whole  motor  system  still  responds  to  stimuli. 

In  small  doses  kava  is  said  to  act  as  a  stimulant  tonic,  but  when  taken  in  large 
amounts  to  produce  an  intoxication  which  differs  from  that  caused  by  alcohol  in 
being  silent,  drowsy,  and  without  emotional  exaltation.  The  great  loss  of  -muscu- 
lar power  which  is  said  to  follow  kava  debauch  in  those  unaccustomed  to  the  use 
of  the  drug  shows  that  its  influence  upon  the  spinal  centres  in  man  is  the  same  as 
in  other  mammals.  According  to  Baldi,  Randolph,  and  Lewin,  the  resin  of  kava 
is  a  local  anaesthetic  of  extraordinary  persistency  of  action,  but  it  appears  to  be  too 
irritant  for  practical  use.  A  decoction  of  the  root  is  used  in  Oceanica  very  largely 
in  the  treatment  ok  gonorrhoea,  and  its  value  has  been  strongly  affirmed  by  Sanne".79 
The  dose  of  the  root  itself,  given  in  decoction,  is  half  a  drachm  three  or  four  times 
a  day  :  of  a  fluid  extract,  half  a  fluidrachm  (2  C.c. ). 

YOHIMBINE. — This  alkaloid  is  obtained  from  the  bark  of  Corynanthe  yohimbi, 
a  rubiaceous  tree,  growing  in  the  southern  Cameroons  district  in  Africa. 

It  was  originally  investigated  by  Oberwarth  and  Loewy,101  who  found  it  was 
in  animals  and  also  in  man  a  very  active  excitant  to  the  sexual  organs  and  func- 
tions. On  the  other  hand,  Kravkoff,  as  the  result  of  experiments  upon  the  lower 
animals  and  upon  man,  concluded  that  it  has  no  aphrodisiac  effect ;  and  frequently 
produces  nausea,  salivation,  irritability,  and  other  disagreeable  results.  It  has  been 
used,  however,  by  numerous  clinicians  in  neurasthenic  impotence,  with  reports 
which  are  generally  favorable  to  its  influence.  (For  literature  see  Merck's  Report, 
1901,  1902. )  It  is  said  to  be  of  no  value  when  impotence  depends  upon  organic 
nerve  trouble,  and  to  be  harmful  when  it  is  caused  by  chronic  inflammatory  disease 
of  the  sexual  organs  or  of  the  prostate  gland.  Dose,  0.005  gramme  of  the  hydro- 
chlorate,  either  in  tablet  or  solution,  three  or  four  times  a  day.  It  has  also  been 
employed  in  a  one  per  cent,  solution  three  times  a  day,  hypodermically. 


LOCAL  REMEDIES. 


REFERENCES. 


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OMELCHENKO 
HOLMFKI.D 
BERNATZIK  .   . 

BERNATZIK  .  . 
HEFFTER  .  .  . 
LEWIN  . 


Sl'TKR      .     . 

CAMMIDGE 
ALBANESE 


86.  MELTZER 


ULRICI    . 
WEISS    . 

RlCHTER 


FAMILY   V.— DIAPHORETICS. 


DIAPHORETICS  are  those  medicines  which  are  employed  to  increase 
the  action  of  the  skin.  It  is  scarcely  in  place  here  to  discuss  the  results 
of  suppression  of  the  functional  activity  of  the  skin  or  the  importance  of 
the  surface-elimination  to  the  system.  It  does  seem  well,  however,  to 
call  attention  to  the  fact  that  the  perspiratory  glands  have  a  double  func- 
tion to  perform, — that  of  elimination,  already  alluded  to,  and  that  of 
keeping  down  the  temperature  of  the  body  during  exposure  to  heat. 
When  a  man  enters  a  Turkish  bath  the  temperature  of  which  is  perhaps 
1 60°  F. ,  or  when  he  works  in  the  sun  on  a  very  hot  day,  there  is,  if  he 
be  used  to  such  exposure,  little  or  no  rise  in  the  temperature  of  the  body, 
because  the  surface-glands  secrete  sweat  so  actively  as  to  expose  a  great 
amount  for  evaporation,  and  by  the  conversion  of  so  much  water  into 
vapor  such  an  amount  of  heat  is  absorbed — i.e.,  converted  from  heat 
into  repulsive  force — that  the  body  is  cooled.  The  reason  that  even  a 
moderate  degree  of  heat  in  a  moist  atmosphere  is  intolerable  is  because 
evaporation  cannot  take  place. 

From  what  has  already  been  stated,  it  is  obvious  that  the  use  of  dry 
external  heat,  or  rather  exposure  to  a  hot  atmosphere,  is  a  powerful 
means  of  producing  perspiration.  It  may  be  applied  either  in  the  form 
of  the  Turkish  bath,  in  which  the  air  of  the  hot  chamber  is  very  dry,  or 
in  the  Russian  or  vapor-bath*  in  which  the  atmosphere  is  surcharged 
with  hot  vapor.  Neither  of  these  baths  has  any  other  physiological 
property  than  that  of  a  sweat-producer. 

Hot-water  baths  offer  another  very  successful  method  of  inducing 
profuse  perspiration.  The  patient  should  be  placed  in  a  bath  of  about 
100°  F.,  and  remain  there  from  fifteen  to  twenty  minutes,  during  which 
time,  by  the  repeated  addition  of  very  hot  water,  the  temperature 
should  be  raised  to  110°  F.,  or  to  such  point  as  the  patient  can  endure. 
Warmed  blankets  having  been  plentifully  provided,  the  sick  man  should 
be  lifted  from  the  bath  into  them,  be  closely  wrapped  up,  and  so  left  for 

*  For  home  use  there  are  in  the  market  various  "  Cabinet  Baths,"  so  called,  which 
afford  a  cheap  and  efficient  means  of  giving  vapor-baths.  The  term  Turkish  bath  is  here 
applied  to  the  bath  used  in  this  country  under  that  name.  This  bath  appears  not  to  be  a 
copy  of  the  Oriental  bath,  but  merely  a  derivative  from  it.  Writers  affirm  that  in  the 
East  the  sudarium,  or  sweating-chamber,  rarely  has  a  temperature  of  more  than  98°  F.  : 
in  London  we  have  been  in  a  Turkish  bath  at  200°  F.  ;  from  140°  to  160°  F.  is  a  common 
temperature  in  American  baths. 


?I8  LOCAL   REMEDIES. 

three  or  four  hours  before  being  transferred  to  the  usual  bed.  According 
to  A.  Steffen,1  after  this  use  of  the  bath  the  body  has  been  proved  to 
undergo  loss  of  weight  continuously  for  one  or  two  days. 

The  popular  belief  that  after  a  sweat  there  is  a  greater  liability  than 
usual  to  take  cold  appears  to  us  to  be  well  founded  :  care  must,  there- 
fore, be  exercised  to  avoid  exposure  after  the  hot  bath  of  any  kind.  The 
liability  to  take  cold  may,  however,  be  overcome  by  the  use  of  the  cold 
douche  or  plunge-bath. 

The  possibilities  of  the  hot-water  bath  as  a  therapeutic  measure  are 
probably  much  greater  than  is  ordinarily  recognized.  In  severe  burns, 
in  nervous  shock,  and  in  various  skin  diseases  continuous  immersion  would 
probably  often  be  found  of  the  greatest  service.  According  to  Baelz,* 
the  baths  which  are  habitually  taken  by  the  entire  native  population  of 
Japan  are  at  a  very  high  temperature  (109°  to  114°  F. ),  and  the  immer- 
sion continuous  during  the  whole  evening.  The  mouth  temperature  rises 
to  104°  or  105°  F. ,  whilst  the  pulse  becomes  very  full  and  increased  in 
frequency,  with  marked  evidences  of  relaxation  of  the  arteries.  When 
there  is  a  high  grade  of  atheroma,  the  softening  of  the  arteries  after  an 
hour's  bath  is  very  pronounced.  Baelz  believes  that  there  is  no  increase 
in  the  elimination  of  nitrogenous  matter,  and  that  the  Japanese  custom  is 
extremely  useful,  because,  the  winter  being  cold  and  the  houses  not 
heated,  the  people  lose  bodily  heat  during  the  day,  and  for  two  pennies 
in  the  evening  acquire  a  supply  of  heat  which  lasts  through  the  night. 

Profuse  sweating  is  always  more  or  less  exhausting,  but  is  not  nearly 
so  much  so  as  purging,  and  therefore  may  be  practised  in  dropsical 
patients  too  feeble  to  allow  of  the  use  of  purgatives.  The  hot  baths  are 
not,  however,  altogether  free  from  danger  or  objection.  Sometimes  in 
the  Turkish  and  Russian  baths  the  patient  fails  to  sweat  freely,  and  a 
feeling  of  distress,  a  bounding,  rapid  pulse,  and  perhaps  severe  headache 
develop  themselves  :  under  these  circumstances  the  bodily  temperature 
rises,  and  a  fever  develops,  which  may  go  on  to  the  production  of -a  true 
' '  thermic  fever, ' '  and  perhaps  terminate  in  sudden  death.  This  is  an 
exceedingly  rare  result,  and  one  that  can  never  occur  if  the  patient  is 
removed  from  the  hot  chamber  so  soon  as  any  unpleasant  symptoms  are 
manifested.  Sudden  death  has  been  recorded  once  from  ' '  sunstroke' ' 
in  a  patient  while  taking  the  ' '  Turkish  bath, ' '  also  once  from  ' '  conges- 
tion of  the  lungs. ' ' 

The  use  of  hot  baths  of  any  kind  is,  of  course,  contra- indicated  by 
the  existence  of  fever  ;  but,  according  to  Steffen,  the  hot- water  baths  are 
pre-eminently  contra-indicated  by  the  existence  of  congestion  or  oedema 
of  the  lungs,  or  of  a  tendency  towards  these  disorders,  since  under  such 
circumstances  the  bath  greatly  increases  the  disease,  or  precipitates  a 
perhaps  fatal  attack.  Our  own  experience  corroborates  these  state- 
ments. We  have  seen,  under  the  conditions  mentioned,  the  most  fright- 
ful dyspnoea  result  from  the  use  of  the  hot-water  bath.  If  disturbance  of 
the  respiration  comes  on  during  the  bath,  the  patient  should  immedi- 


DIAPHORETICS.  719 

« 

ately  be  taken  out,  and,  if  the  symptoms  be  urgent,  cold  water  should  be 
freely  dashed  over  the  head,  neck,  and  chest.  Severe  cardiac  disease  is 
also  a  centra-indication  both  to  the  Turkish  and  Russian  or  vapor-bath. 

Precisely  as  water  may  act  as  a  diuretic  by  increasing  the  fluidity  and 
amount  of  blood,  so  may  it  also  act  as  a  diaphoretic,  provided  that  it  is 
directed  to  the  skin  by  being  itself  given  warm  and  aided  by  the  use  of 
external  heat ;  hence  the  importance  of  hot  drinks  when  it  is  desired  to 
produce  free  sweating.  The  colliquative  so-called  "  night- sweats  "  of 
phthisis  are  undoubtedly  largely  due  to  a  paralytic  weakening  of  the 
blood-vessels  of  the  skin.  In  similar  manner  aconite,  veratrum  viride, 
tartar  emetic,  and  other  substances  which  profoundly  affect  the  vaso-motor 
system  produce  a  free  sweating  which  resembles  that  often  seen  in  col- 
lapse from  other  than  drug  causes. 

Diaphoretics  are  employed  in  the  practice  of  medicine  to  fulfil  the 
following  indications  : 

First.  To  arrest  forming  diseases  of  not  very  severe  type,  probably 
by  causing  a  flow  of  blood  to  the  surface,  and  thereby  relieving  slight 
internal  congestions,  and  possibly  by  eliminating  principles  which  have 
been  retained  in  the  blood  instead  of  being  excreted  as  they  ought  to 
have  been.  In  general  cold,  in  muscular  rheumatism,  in  suppressed  men- 
struation, and  other  results  of  exposure  to  cold  and  of  checked  perspira- 
tion, the  diaphoretics  afford  the  most  efficient  means  at  our  command  for 
restoring  the  normal  functions. 

Second.  To  favor  absorption.  In  dropsy  the  diaphoretics  are  of  very 
great  value,  often  aiding  diuretics  and  purgatives  in  effecting  a  cure,  and 
sometimes,  when  these  fail,  or  when  circumstances  forbid  their  use, 
rescuing  the  patient  from  impending  death.  None  of  the  medicinal 
diaphoretics  except  jaborandi  is  of  sufficient  power  to  be  relied  upon 
in  dropsy.  The  Turkish,  the  Russian,  and  the  hot-water  bath  are  capa- 
ble of  producing  sufficient  sweating  to  cause  absorption  of  dropsical 
fluid,  but  must  be  vigorously  employed. 

Third.  To  aid  in  the  subsidence  of  diseases  which  naturally  pass  off 
with  a  sweat.  The  chief  use  of  diaphoretics  for  this  purpose  is  in 
miasmatic  fevers,  especially  in  the  remittent  form  of  the  affection,  when 
the  sweating  stage  fails  to  develop  itself  thoroughly  and  the  paroxysms  run 
into  one  another.  Even  in  the  single  paroxysm  of  intermittent  fever,  by 
hastening  the  closing  stage,  diaphoretics  will  often  shorten  the  paroxysm. 

Fourth.  To  eliminate  noxious  materials  from  the  blood.  The  old 
humoral  idea  that  the  groundwork  of  such  diseases  as  fevers  is  a  dis- 
tinct matcrics  morbi  which  can  be  eliminated  from  the  blood  has  no 
sufficient  demonstration  to  be  accepted,  and,  although  diaphoretics  do 
good  in  fevers,  yet  it  cannot  be  granted  that  it  is  in  this  manner.  The 
very  great  power  of  increased  diaphoresis  in  cooling  the  body  through 
surface-evaporation  has  already  been  dwelt  upon,  and  much  of  the  good 
effected  by  diaphoretics  in  diseases  of  high  temperature  probably  has  its 
origin  in  this  power. 


720  LOCAL    REMEDIES. 

Modern  science  seems  clearly  to  point  out  that  diaphoretics  may 
aid  in  separating  from  the  blood  retained  secretions,  and  may  to  some 
extent  replace  the  action  of  the  kidneys  when  these  organs  are  disabled 
by  disease. 

In  1851  Schottin*  discovered  urea  in  the  sweat  of  patients  suffering  from  the 
collapse  of  cholera.  Not  only  has  the  discovery  of  Schottin  been  confirmed  by  the 
researches  of  G.  O.  Rees,5  of  Fiedler,6  of  Hirschsprung,7  of  Kaup  and  Jiirgensen,9 
of  Leube,9  and  of  G.  Deininger,10  but  it  has  also  been  abundantly  proved  that  the 
skin  excretes  urea  freely  during  the  advanced  stages  of  Bright' s  disease,  and  also 
during  the  partial  urinary  suppression  of  scarlatinal  desquamative  nephritis.  The 
urea  in  renal  disease  may  even  form  a  distinct  crystalline  powder  on  the  skin,  but 
it  is  most  abundant  about  the  mouths  of  the  sweat-glands.  We  believe  Landerer 
was  the  first  to  announce  that  urea  is  present  in  the  sweat  of  healthy  persons ; 
and,  although  excellent  chemists  have  been  unable  to  detect  it,  its  presence  at 
times  can  no  longer  be  denied,  since  it  has  been  found  not  only  by  Landerer,  but  also 
by  Funke11  in  1858,  by  Meissner,12  and  by  Leube  ;  Fourcroy  (quoted  by  Rees)  has 
also  found  it  in  the  sweat  of  horses.  By  a  series  of  elaborate  experiments,  Leube 
has  rendered  it  probable,  if  he  has  not  actually  proved,  that  in  health  there  is  such 
a  relation  between  the  skin  and  the  kidneys  that  when  the  former  is  very  active  the 
latter  excrete  less  than  the  normal  amount  of  urea. 

When  to  the  facts  already  cited  are  added  the  observation  of  Grie- 
singer,  that  in  diabetes  the  perspiration  contains  sugar,  and  the  well- 
known  circumstances  that  in  rheumatism  the  sweat  contains  lactic  acid, 
and  in  jaundice  biliary  products,  the  value  of  diaphoretics  as  a  means  of 
getting  rid  of  retained  excretions  becomes  manifest.  For  this  reason, 
in  Bright1  s  disease,  especially  of  the  acute  form,  they  are  of  the  greatest 
value,  acting  beneficially  in  three  different  ways, — by  drawing  the  blood 
to  the  surface,  and  thereby  relieving  any  internal  congestions  of  the 
kidneys  or  other  organs  that  may  exist  ;  by  promoting  the  absorption  of 
dropsical  effusions  ;  and  by  eliminating  retained  secretions. 

PILOCARPUS.     U.S.— JABORANDI. 

This  drug,  which  has  long  been  employed  by  the  natives  of  South 
America,  received  its  first  notice,  under  the  various  names  of  Jaborandi, 
Jaguarandy ',  and  Jamguarandi,  from  T.  J.  H.  Langgaard  in  his  Dic- 
cionario  de  Mededna  domestica,  Rio  Janeiro,  1865.  It  attracted  no 
attention,  however,  until  1874,  when  it  was  brought  to  Paris  by  Cou- 
tinho.  The  leaves  *  alone  are  official  ;  of  them  there  are  in  commerce 
two  varieties  :  the  Rio  Janeiro  Jaborandi,  which  is  believed  to  be  the 
product  of  Pilocarpus  selloanus,  and  the  Pernambuco  Jaborandi,  the 
product  of  P.  Jaborandi.  The  two  varieties  agree  in  that  the  leaves 
are  oval,  oblong,  and  entire,  four  to  six  inches  long  and  one  and  a 
half  to  two  inches  wide,  with  a  bitter  taste  and  a  hay-like  odor  :  they 
differ  in  that  the  Rio  Janeiro  leaves  have  a  tendency  to  become  obovate 

*  Under  the  name  of  Jaborandi  various  drugs  other  than  the  product  of  Pilocarpus 
are  sold  in  Brazil.  As  the  Pilocarpus  pinnatus  has  been  found  to  be  active  when  grown 
in  France,  it  is  probable  that  the  Jaborandi  plant  might  be  successfully  cultivated  in  our 
Southern  States.  Frerichs  (Berlin.  Klin.  Wochenschrift,  1875)  found  the  wood  inert. 


DIAPHORETICS.  721 

in  shape  and  are  not  prominently  veined  upon  the  upper  surface,  whilst 
in  the  Pernambuco  leaves  the  upper  venation  is  very  pronounced.  Each 
variety  contains  the  alkaloid  pilocarpine,  discovered  by  Byarson,*  but 
the  Pernambuco  leaves  are  said  to  be  much  the  richer. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Absorption  and  Elimina- 
tion.— Jaborandi  is  practically  free  from  irritant  properties,  and  yields  its 
active  principle  rapidly  in  the  alimentary  canal.  After  hypodermic  in- 
jection of  pilocarpine  the  symptoms  may  set  in  in  five  minutes.  It  is 
probable  that  the  alkaloid  escapes  from  both  the  skin  and  kidneys. 

General  Effects. — When  an  infusion  of  from  sixty  to  ninety  grains  of 
Jaborandi  is  given  to  an  adult,  in  about  ten  minutes  the  face  and  neck 
become  deeply  flushed,  and  free  perspiration  and  salivation  commence. 
The  sweating  begins  on  the  face  ;  both  it  and  the  salivation  are  exces- 
sively profuse,  and  last  from  three  to  five  hours.  There  is  not  rarely 
nausea,  and  sometimes  vomiting.  The  pulse  is  usually  more  or  less 
quickened,  .as  is  also  frequently  the  respiration.  After  the  sweating 
has  ceased,  the  patient  is  left  more  or  less  exhausted.  The  nasal  and 
lachrymal  secretions  are  also  very  generally  increased  under  the  action 
of  the  drug,  and  Gubler  has  noted  diarrhoea,  which  in  the  experiments 
of  Ringer  and  others  has  not  been  present.  There  is  sometimes  con- 
traction of  the  pupils,  and  even  disturbance  of  vision.  These  effects  of 
the  drug  are  in  the  adult  fairly  constant ;  but  subjects  have  been  occa- 
sionally found  who  were  not  susceptible  to  the  action  of  the  remedy,  and, 
very  curiously,  in  Ringer's  experiments  children  were  found  to  be  very 
insusceptible,  although  doses  of  sixty  grains  were  employed.  Schwann, 
Moral,  and  other  observers  have  noticed  in  the  lower  animals  that  very 
violent  gastric  and  intestinal  movements  are  produced  by  the  drug. 

Secretion. — The  sweat  produced  by  Jaborandi  is  often  enormous  in 
quantity  (nine  to  fifteen  ounces  by  estimation).  It  is  stated  to  be  at 
first  acid,  then  neutral,  and  finally  clearly  alkaline.  Vulpian  IS  denies  that 
even  the  first  sweat  has  other  than  alkaline  reaction,  and  believes,  with 
Luchsinger  and  Trumpy,  that  there  has  been  a  mistaken  observation,  due 
to  the  fact  that  the  secretion  of  the  sebiferous  glands  is  acid.  In  the 
analyses  of  Robin  the  chlorides  were  found  in  excess,  the  carbonates  and 
phosphates  in  very  minute  amount,  and  the  urea  in  more  than  five  times 
its  normal  proportion,  the  amount  eliminated  in  the  sweating  being  esti- 

*  Concerning  the  alkaloids  of  Jaborandi  and  their  derivatives  there  is  much  confusion 
and  imperfection  in  our  knowledge.  Three  alkaloids  have  been  thought  to  exist  in 
Jaborandi  leaves,  namely,  pilocarpine  and  its  derivatives,  jaborine  and  pilocarpidine. 
According  to  its  discoverers,  Harnack  and  Meyer  (A.  E.  P.  P.,  xii.),  jaborine  acts  upon 
the  heart,  pupil,  intestines,  and  salivary  glands  in  a  manner  almost  identical  with  that 
of  atropine,  so  that  its  occasional  presence  in  commercial  pilocarpine  gives  rise  to  vagaries 
of  physiological  and  therapeutic  action.  Jowett,  however,  has  been  unable  to  isolate 
jaborine,  and  there  is  much  doubt  as  to  its  being  a  constant  constituent  of  Jaborandi. 
(See  Marshall,  B.  M.,  1900,  ii.).  Further,  according  to  Marshall,  jaborine  sold  by  Merck 
is  a  mixture  of  pilocarpine  and  a  fourth  alkaloid,  isofiilocarpine.  Pilocarpidine,  according 
to  Harnack  (A.E.P.P.,  xx.),  causes  in  excessive  dose  violent  sweating,  salivation,  also 
vomiting  and  purging,  with  great  disturbances  of  circulation. 

46 


722  LOCAL   REMEDIES. 

mated  at  from  ten  to  fifteen  grains.  Hardy  and  Ball "  believed  that  in 
their  experiments  the  average  amount  of  urea  eliminated  by  the  skin  was 
seventeen  grains. 

Jaborandi  appears  to  have  an  extraordinary  influence  upon  secreting 
glands,  not  only  in  the  skin  but  almost  throughout  the  whole  body. 
The  nasal  mucus  is  often  greatly  increased.  The  assertion  of  Pilicier,15 
that  in  a  dog  with  a  gastric  fistula  the  gastric  juices  were  greatly  in- 
creased by  the  drug,  is  in  conformity  with  the  free  vomiting  of  large 
quantities  of  glairy  secretion  which  it  causes  in  man.  Morat 16  has 
noted  a  temporary  increase  of  the  sugar  in  the  blood,  an  evidence  that 
the  glycogenic  function  of  the  liver  is  stimulated.  The  suprarenal  cap- 
sules appear  to  share  the  action  of  the  drug,  since  Auguste  Pettit "  has 
noticed  that  in  animals  poisoned  by  jaborandi  there  is  marked  conges- 
tion and  swelling  of  these  bodies.  On  account  of  the  antagonism  be- 
tween the  skin  and  the  kidneys  the  diaphoretic  dose  of  pilocarpine  may 
cause  a  decrease  in  the  urinary  flow,  but  the  assertion  of  Gubler  that 
the  alkaloid  administered  in  very  small  repeated  doses  has  a  marked 
diuretic  influence  has  received  clinical  confirmation.*  According  to 
Gottlieb,18  pilocarpine  causes  an  increase  of  both  the  watery  and  solid  con- 
stituents of  the  pancreatic  secretion. 

There  appears  to  be  some  relation  between  the  flow  of  saliva  and 
that  of  perspiration  produced  by  jaborandi  :  if  the  one  is  very  profuse 
the  other  is  often,  but  not  always,  correspondingly  scanty.  Sometimes 
the  salivation  almost  replaces  the  sweating  (Fereol 19)  ;  very  frequently 
it  commences  before  the  sweating,  and  often  it  is  more  persistent. 
During  it  the  mouth  is  warm,  and  there  is  often  a  feeling  of  tenseness 
about  the  maxillary  glands.  The  saliva  contains  an  abundance  of  salts 
and  of  ptyalin,  as  well  as  a  small  excess  of  urea.  Pilicier,  it  is  true, 
states  that  the  proportion  of  albuminous  compounds,  and  especially  of 
potassium  sulphocyanide,  is  much  diminished,  but  in  Robin's  analyses 
the  proportion  was  even  beyond  the  normal,  and  Ch.  Bougarel  has  by 
careful  experimentation  shown  that  the  power  of  jaborandi -saliva  in  con- 
verting starch  into  sugar  is  equal  to  that  of  the  normal  secretion.  Ac- 
cording to  J.  N.  Langley,  in  the  frog  the  mouth  and  skin,  after  the 
exhibition  of  jaborandi,  become  covered  with  a  viscid  secretion  ;  in  the 
dog,  the  rabbit,  and  the  cat  there  is  profuse  salivation. 


*  Much  interest  attaches  to  the  effect  of  jaborandi  upon  urea-elimination,  but  it  can- 
not be  considered  as  determined,  except  that  in  various  diseases  the  combined  renal  and 
dermal  elimination  is  greatly  increased  by  the  drug.  Hardy  and  Ball  state  that  in  health 
urea-elimination  from  the  kidneys  is  diminished  by  the  drug,  while  Tyson  and  Bruen 
have  found  it  increased  both  in  health  and  in  disease.  The  experiments  have,  however, 
been  too  few,  and  especially  the  conditions  of  their  performance  too  lax,  for  much  im- 
portance to  be  attached  to  them.  As  the  result  of  experiments  upon  the  lower  animals,  J. 
Horbaczewski  (  Therap.  Gaz.,  1893)  believes  that  there  is  a  distinct  relation  between  the 
elimination  of  uric  acid  and  the  number  of  leucocytes  in  the  blood,  and  that  pilocarpine  in 
proper  dose  increases  the  size  of  the  spleen  and  increases  also  the  number  of  leucocytes 
in  the  blood  and  the  quantity  of  uric  acid  eliminated. 


DIAPHORETICS.  723 

The  action  of  pilocarpine  in  increasing  secretion  is  direct  and  upon 
the  glands  themselves.  The  salivary  glands  are  affected  equally  before 
and  after  section  of  all  of  the  salivary  nerves  (Langley20  and  Carville," 
confirmed  by  Schwann  M  ) ;  also  when  the  drug  is  injected  directly  into  the 
gland  and  prevented  from  entering  the  general  circulation  (Langley). 
According  to  the  elaborate  experiments  of  Langley  upon  cats  poisoned 
with  pilocarpine,  stimulation  of  the  chorda  tympani  or  of  the  sympathetic 
nerve  causes  respectively  some  increase  or  lessening  of  the  secretion,  but 
this  increase  or  lessening  is  not  nearly  equal  to  that  which  occurs  in  the 
normal  animal,  and  is  due  to  the  action  of  the  nerves  upon  the  circula- 
tion, and  not  to  any  influence  on  their  secretory  fibres.  Very  large  doses 
of  the  drug  injected  into  the  gland  immediately  arrest  the  accretion,  and 
doses  of  less  size  given  in  the  same  way,  while  increasing  secretion,  para- 
lyze both  chorda  tympani  and  sympathetic  nerve,  so  that  stimulation  of 
them  has  no  effect.  It  is  probable  from  the  last  fact  that  jaborandi  has 
an  action  upon  the  secretory  gland- cells. 

Although  the  evidence  just  deduced  indicates  that  an  influence  is  exerted  by 
jaborandi  upon  the  gland-cells,  the  fact  that  atropine  arrests  the  jaborandi  salivary 
secretion  prevents  us  from  considering  it  entirely  settled  that  the  drug  does  so  act 
upon  the  salivary  gland-cells  rather  than  upon  the  peripheral  nerve-endings,  since 
there  is  reason  for  believing  that  atropine  acts  upon  the  nerve-endings.  Fuchsinger 
(confirmed  by  Nawrocki)  has  found  that  section  of  the  nerves  of  the  cat's  leg  did 
not  prevent  the  paws  from  sweating  when  jaborandi  was  exhibited.  This  demon- 
strates that  the  action  of  the  drug  is  peripheral,  not  centric.  Five  or  six  days  after 
the  section,  when  the  peripheral  nerve-endings  had  undergone  degeneration, 
Fuchsinger  found  that  jaborandi  was  unable  to  excite  sweating.  This,  however, 
can  hardly  be  considered  to  prove  absolutely,  as  Fuchsinger  ra  asserts,  that  the  drug 
acts  upon  the  peripheral  nerve-endings  and  not  directly  upon  the  glandular  cells 
themselves,  since  it  is  probable  that  these  glandular  cells  shared  the  anatomical 
changes  of  the  nerve-endings. 

Jaborandi  appears  to  stimulate  the  nutrition  of  the  hair,  and  Pren- 
tiss,24  of  Washington,  has  reported  several  cases  in  which  the  continued 
internal  use  of  pilocarpine  caused  the  hair  to  become  exceedingly  coarse 
and  to  change  its  color  from  light  to  dark.  H.  Rasori 25  has  noticed  a 
tuberculated  eruption  apparently  produced  by  jaborandi.  M.  Grocco  ** 
has  found  that  pilocarpine  hypodermically  injected  or  locally  applied  sen- 
sibly affects  hysterical  anaesthesia. 

Temperature. — Robin  affirms  that  before  and  during  the  early  stages 
of  the  sweating  from  jaborandi  the  temperature  rises  i°  to  2°  F. ,  but 
afterwards  falls  as  much  below  the  normal  point  and  remains  depressed 
for  one  or  two  days.  This  primary  rise  of  temperature  has  been  noted 
by  other  observers/11  but  is  frequently  absent  altogether  or  very  trifling,  f 

*  See  Ringer  {Lancet,  1873,  i.  157),  Greene  (Phila.  Med.  Times,  vi.  56),  Scotti  (Ber- 
lin. Klin.  Wochens.,  1877,  141),  Pilicier  (Med.  Centralbl.,  1876,429),  and  Weber  (Ibid., 
770).  Pilicier  noted  that  the  rise  occurred  in  the  axilla,  but  not  in  the  rectum  :  this  would 
indicate  that  it  is  a  local  phenomenon,  the  result  of  a  heating  of  the  surface,  not  of  the 
interior,  of  the  body. 

|  Consult  Riegel  (Berlin.  Klin.  Wochens.,  1875,  86),  Bardenhewer  (Ibid.,  1877,  8),  and 
Auschmann  (Ibid.,  353). 


724  LOCAL   REMEDIES. 

The  subsequent  fall  of  temperature,  which  is  a  constant  phenomenon, 
probably  depends  in  great  part,  or  altogether,  upon  the  loss  of  heat 
during  the  sweating. 

Nutrition. — The  interesting  question  whether  the  excessive  secretion 
of  solids  from  the  skin  and  urine  produced  by  pilocarpine  is  accompanied 
by  any  increase  of  waste  products  in  the  body,  or  is  only  due  to  an  in- 
creased activity  of  the  glands  in  clearing  out  waste  products  already  pro- 
duced, cannot  at  this  time  be  answered.  According  to  Otto  Frank  and 
Fritz  Voit,46  the  first  dose  of  the  alkaloid  causes  in  the  curarized  dog 
increased  elimination  of  carbonic  acid,  but  a  second  dose,  given  when 
the  carbonic  acid  elimination  has  returned  to  the  norm,  has  no  such 
effect  ;  it  is  therefore  probable  that  the  drug  has  no  direct  influence  upon 
nutrition. 

Circulation. — The  action  of  jaborandi  upon  the  circulation  has  been 
studied  by  Langley,27  E.  Ley  den, M  Kahler  and  Sayka,29  and  Harnack 
and  Meyer.80  The  phenomena  noted  by  these  observers  are  in  most 
respects  in  accord,  but  Kahler  and  Sayka  using  the  extract  of  jaborandi, 
and  E.  Leyden  commercial  pilocarpine,  have  found  the  pulse  either  as  a 
constant  or  occasional  phenomenon  at  first  increased  in  its  rate,  while 
Harnack 31  has  never  seen  this  with  chemically  pure  pilocarpine.  It  has 
been  shown,  however,  by  E.  T.  Reichert32  that  the  result  reached  by 
Harnack  was  not  due  to  the  purity  of  the  alkaloid,  but  to  his  not  having 
used  sufficiently  minute  doses.  According  to  Reichert' s  experiments, 
the  minute  dose  increases,  the  large  dose  decreases,  the  pulse-rate,  there 
being  a  broad  line  between  the  two  effects  in  which  the  pulse  is  normal. 
Immediately  after  the  injection  of  the  alkaloid  into  the  jugular  vein  the 
arterial  pressure  falls,  but  in  a  few  moments  the  characteristic  phenomena 
of  a  slow  pulse  with  increased  arterial  pressure  come  on.  This  slowing 
of  the  pulse  is  not  prevented  by  previous  section  of  the  pneumogastric, 
but  is  at  once  set  aside  by  an  injection  of  atropine  (Langley,  Leyden, 
Harnack  and  Meyer),  as  is  also  the  diastolic  arrest  of  the  heart  which  pilo- 
carpine produces  in  the  frog.  Harnack  and  Meyer  therefore  believe  that 
in  both  the  frog  and  the  mammal  the  chief  cardiac  influence  of  the  alka- 
loid is  exerted  upon  the  intra-cardiac  inhibitory  ganglia  ;  but  Ringer M 
finds  that  jaborandi  and  atropine  act  antagonistically  upon  the  ventricles 
separated  from  the  auricles,  and,  as  the  ventricles  contain  no  inhibitory 
ganglia,  some  other  explanation  of  the  antagonism  must  be  found.*  The 
rise  of  the  arterial  pressure  is  stated  by  Harnack  and  Meyer  to  be  pre- 
vented by  the  use  of  curare  and  artificial  respiration,  and  to  be,  there- 
fore, a  secondary,  not  a  direct,  result  of  the  drug's  action  :  it  is  probably 
due  to  the  convulsive  muscular  contractions  produced  by  the  drug.  In 
the  latter  stage  of  the  poisoning  the  arterial  pressure  falls.  As  in  the 

*  Ringer's  explanation  seems  at  present  the  most  probable.  It  is,  that  pilocarpine 
paralyzes  the  heart  by  combining  with  the  molecules  of  the  excito-motor  apparatus  and 
of  the  muscular  tissue,  and  that  atropine  displaces  the  pilocarpine  and  thereby  substi- 
tutes its  own  action. 


DIAPHORETICS.  725 

experiments  of  Harnack  and  Meyer  asphyxia  in  this  stage  did  not  cause 
rise  of  pressure,  although  the  heart  appeared  still  to  retain  its  force,  the 
vaso-motor  system  is  probably  paralyzed,  a  conclusion  confirmed  by  the 
later  experiments  of  Reichert.  The  pulse  still  continues  slow,  although, 
according  to  Harnack,  the  vagi  are  completely  paralyzed. 

Respiration. — According  to  the  experiments  of  Morat  and  Doyon," 
pilocarpine  produces  a  distinct  slowness  of  the  respiration,  and  as  a 
respiratory  poison  is  the  antagonist  to  atropine.* 

Sexual  Organs. — Jaborandi  does  not  appear  to  have  any  power  over 
the  sexual  organs,  except  the  pregnant  womb.  Cases  of  abortion  during 
its  use  have  been  reported  by  Masmann  (quoted  by  Larvand  K)  and  by 
Schanta,36  but  in  the  hands  of  other  observers  the  drug  has  appeared  to 
have  little,  if  any,  abortifacient  influence,  and  Hyernaux  and  Chanteril 
have  found  it  powerless  in  the  lower  animals  (quoted  by  Larvand).  When, 
however,  the  pregnant  female  is  at  her  full  term,  the  drug  may  affect  the 
uterine  contractions,  as  Larvand  and  others  have  noted  an  increase  of 
the  pains,  or  even  a  precipitation  of  labor,  both  in  women  and  in  the 
lower  animals.  Nevertheless,  the  oxytocic  powers  of  jaborandi  are  very 
feeble.f 

Motor  System. — In  man,  muscular  tremblings  have  been  observed 
during  the  action  of  jaborandi,  but  it  is  doubtful  whether  they  are  due 
to  a  direct  action  of  the  remedy.  In  the  frog,  as  first  noticed  by  Mur- 
rell,37  small  doses  (three  milligrammes  of  pilocarpine)  produce  violent 
convulsions  with  heightened  reflex  activity,  while  larger  amounts  cause 
complete  palsy.  According  to  Harnack  and  Meyer,  the  convulsions  are 
due  to  spinal  stimulation,  and  the  paralysis  partly  to  overwhelming  of  the 
spinal  centres  and  partly  to  paralysis  of  the  muscles,  the  motor  nerves 
themselves  not  being  affected.  The  action  of  the  drug  upon  the  mus- 
culo-nervous  system  is  entirely  subservient  to  its  other  effects. 

Eye. — When  applied  to  the  eye,  pilocarpine  produces  contraction  of 
the  pupil,  tension  of  the  accommodative  apparatus,  and  an  approxima- 
tion of  the  near  and  far  points  of  distinct  vision.  \  Tweedy  also  states 
that  there  is  impairment  of  vision,  due  to  benumbing  of  the  retina. 
According  to  P.  Albertoni,  the  myosis  is  followed  by  a  moderate  but 
persistent  mydriasis,  and  is  not  prevented  by  previous  section  of  the 
oculo-motor  nerve  or  of  the  upper  cervical  sympathetic  ganglion.  It  is 
certainly  the  result  of  a  peripheral  influence.  Galezowski,  who  uses  a 
solution  of  one  part  of  a  pilocarpine  salt  in  fifty  parts  of  water,  affirms 
that  it  answers  as  well  as  a  solution  of  eserine  in  diseases  of  the  eye,  and 
has  the  great  advantage  of  not  producing  irritation. 

*  H.  Dreser  (Arch.f.  Exper.  Path.  «.  Pharm.,  1892,  xxx.)  has  experimentally  found 
that  pilocarpine  markedly  increases  the  oxygen  in  the  air  of  the  swimming  bladder  of  the 
carp. 

t  See  British  Medical  Journal,  1879,  ii.  509  ;  alsoWu-H.  Med.  Bliitt.,  1879,  ii.  1178,  1207. 

j  See  John  Tweedy  (Lancet,  1875,  i.  159),  C.  Scotti  (Berl.  Klin.  Wochens.,  1877,  143). 
and  Galezowski  ( Med.  Times  and  Gaz.,  1877,  ii.  358). 


726  LOCAL   REMEDIES. 

THERAPEUTICS. — Jaborandi  is  by  far  the  most  reliable  and  powerful 
remedy  of  its  class,  and  is  always  selected  when  it  is  desired  to  produce 
a  very  active  sweating,  as  in  jircemia  or  in  dropsy.  Both  in  acute  and 
chronic  Bright' s  disease  it  is  of  very  great  value,  either  as  an  aid  to  or  as 
a  succedaneum  for  the  vapor-baths.  The  sweating  should  be  repeated 
at  regular  intervals,  varying  from  one  a  day  to  one  a  week,  according  to 
the  nature  of  the  case. 

Not  only  is  jaborandi  valuable  for  the  removal  of  distinctly  excremen- 
titious  material  from  the  blood,  but  it  is  often  of  the  greatest  service  in 
arresting  the  development  of  a  forming  disease,  probably  by  eliminating 
peccant  matters.  Thus,  in  the  onset  of  an  attack  of  influenza,  in  the  be- 
ginning of  a  bilious  fever,  and  in  subacute  and  muscular  rheumatism  it  may 
often  be  used  with  great  advantage.  On  the  other  hand,  when  in  a  fever 
it  is  desired  not  to  produce  a  single  excessive  sweating,  but  simply  to 
maintain  moisture  of  the  skin,  jaborandi  will  hardly  serve  the  purpose  of 
the  practitioner,  and  in  typhoid  or  other  asthenic  fevers  more  or  less 
danger  of  exhaustion  attends  its  use. 

In  doses  of  from  one-twelfth  to  one-fifteenth  of  a  grain  (0.005-0.004 
Gm.  ),  given  every  two  to  four  hours,  pilocarpine  usually  causes  a  decided 
increase  in  the  secretion  of  urine,  and  is  a  valuable  remedy  in  the  treat- 
ment of  cardiac  and  of  renal  dropsies.  In  rare  cases  albuminuria  and 
even  strangury  *  have  followed  this  use  of  the  drug,  so  that  some  caution 
would  seem  to  be  necessary  in  its  employment  in  the  early  stages  of  acute 
nephritis.  Nevertheless,  we  have  seen  it  apparently  successful  in  acute 
suppression  of  urine. 

In  the  treatment  of  pseudo-membranous  laryngitis  and  in  diphtheria 
pilocarpine  was  at  one  time  extensively  used,  under  the  belief  that  by  in- 
creasing the  secretion  beneath  the  membranes  it  would  loosen  them  ;  it 
has,  however,  failed  to  establish  its  value  for  this  purpose.  Ringer S8  has  re- 
ported several  cases  of  unilateral  sweating  cured  by  the  use  of  full  doses  of 
pilocarpine  given  hypodermically.  It  has  been  used  with  asserted  suc- 
cess in  alopecia.  Cheron  affirms  that,  when  given  in  doses  of  one-twelfth 
of  a  grain  hypodermically,  pilocarpine  is  very  effective  as  a  galactagogue, 
but  Ch.  Cornevin  w  found  that  in  cows,  at  least,  pilocarpine  has  no  influ- 
ence upon  the  quantity  of  milk  secreted,  though  it  increases  the  produc- 
tion of  lactose. 

Locally  applied  (half-ounce  of  the  leaves)  in  the  form  of  a  poultice, 
jaborandi  may  sometimes  produce  local  sweating  only,  but  we  have 
seen  very  marked  and  extraordinarily  prolonged  general  sweating  so 
caused. 

The  Use  of  Pilocar'pine  in  Diseases  of  the  Eye.^ — The  instillation  of 
a  one  per  cent,  solution  of  pilocarpine  hydrochlorate  into  the  eye  is  fol- 
lowed by  exactly  the  same  results  as  those  which  have  been  described  in 

*  See  Purjesz  (Deutsch.  Arch.f.  Klin.  Med.,  xvii.  533)  ;  also  Stumpf  (Deutsch.  Arch., 
xvi.). 

t  This  section  was  written  by  Professor  George  E.  de  Schweinitz. 


DIAPHORETICS.  727 

connection  with  eserine.  Pilocarpine  fulfils  all  the  therapeutic  indications 
of  eserine.  It  is  not,  however,  as  active,  and  therefore  the  strength  of 
the  solution  used  must  be  greater.  It  has  the  advantage  of  being  less 
irritating  and  less  liable  to  cause  iritis. 

ADMINISTRATION. — The  fluid  extract  of  jaborandi  (FLUIDEXTRACTUM 
PILOCARPI,  U.  S. )  may  be  given  in  doses  of  half  a  drachm  to  a  drachm 
(2-4  C.c. ),  but  is  inferior  to  the  alkaloid  in  being  more  uncertain  and 
more  liable  to  nauseate.  Dose  of  the  nitrate  or  hydrochlorate  (PiLOCAR- 
PINE  HYDROCHLORAS,  U.  S.,  PILOCARPINE  NITRAS,  U.  S. ),  from 
one-eighth  to  one-third  of  a  grain  (0.008—0.02  Gm. ).  In  larger  doses 
it  is  capable  of  producing  so  severe  sweating  as  to  end  in  collapse. 
Even  pilocarpine,  however,  is  apt  to  cause  vomiting,  and  we  have 
found  that  when  it  is  desirable  to  produce  an  excessive  sweating  for  the 
purpose  of  breaking  up  a  forming  disease,  much  better  results  may  be 
obtained  by  conforming  to  the  following  procedure  than  by  giving  pilo- 
carpine unaided:  let  the  patient,  prepared  for  bed,  take  one  dessert- 
spoonful of  a  mixture  containing,  to  the  dessertspoonful,  one-twelfth  of  a 
grain  of  pilocarpine  hydrochlorate,  five  grains  of  antipyrin,  and  one  to 
three  minims  of  tincture  of  aconite-root  ;  soak  the  feet  fifteen  minutes  in 
a  hot  mustard  bath  ;  on  getting  into  bed  take  a  teaspoonful  of  the  pilo- 
carpine mixture,  with  a  tumbler  of  very  hot  lemonade  or  whiskey 
punch  ;  repeating  every  twenty  minutes  the  pilocarpine  mixture  until 
free  perspiration  sets  in. 

Antagonism,  with  Atropine. — In  1875  Langley  *°  called  attention  to 
the  antagonism  existing  between  jaborandi  and  belladonna.  When  the 
heart  has  been  slowed  or  arrested  by  jaborandi,  atropine  will  bring  the 
rate  of  pulsation  almost  to  normal  ;  the  reverse  of  this  also  occurs,  pro- 
vided the  amount  of  atropine  previously  applied  has  not  been  too  great 
(Langley).  Upon  the  sweat-glands  the  two  drugs  have  also  antagonistic 
powers,  one  being  able  to  annul  the  action  of  the  other  (Fuchsinger). 
The  same  is  true  in  regard  to  the  salivary  secretion  (Langley).  This 
antagonism  between  atropine  and  jaborandi  is  affirmed  by  H.  Larvand 
to  extend  to  the  intestines  and  pupil.  In  belladonna-poisoning  the  alka- 
loid has  been  used  with  no  advantage  in  very  small  dose,41  but  in  a  case 
in  which  nine-tenths  of  a  grain  of  atropine  had  been  taken,  nine  grains 
of  pilocarpine  are  said  to  have  been  injected  hypodermically  in  between 
one  and  two  hours  with  success  (Purjesz").  L.  Juhasz"  reports  a  case 
in  which  it  was  estimated  that  about  one  and  a  half  grains  of  atropine 
were  taken,  followed  in  half  an  hour  by  vomiting  ;  four  and  a  half  grains 
of  pilocarpine  were  injected  in  about  seven  hours,  with  a  favorable  result. 
Hofferts u  reports  a  case  in  which  seven  and  a  half  grains  of  extract  of 
"belladonna  were  ingested,  and  nearly  two  grains  of  pilocarpine  given, 
with  recovery.* 

*  For  other  cases  of  like  import,  see  I^ancet,  1890,  ii. ;  also  Therap.  Gaz.,  1887 


728  LOCAL    REMEDIES. 

SPIRITUS  ^THERIS  NITROSI— SPIRIT    OF  NITROUS  ETHER.     U.  S. 

Sweet  spirit  of  nitre  is  an  alcoholic  solution  of  ethyl  nitrite.  It  is 
soluble  in  all  proportions  in  water  and  alcohol,  and  has  a  neutral  reaction, 
is  a  volatile,  inflammable  liquid,  of  a  pale  yellow  color  inclining  slightly 
to  green,  having  a  fragrant,  ethereal  odor,  free  from  pungency,  and  a 
sharp,  burning  taste.  It  has  the  specific  gravity  0.836  100.842,  and 
contains  4.3  per  cent,  of  its  peculiar  ether.  It  should  not  be  long  kept, 
as  it  becomes  acid  by  age. 

Sweet  spirit  of  nitre  when  taken  freely  in  the  form  of  fumes  may 
cause  symptoms  of  nitrous  acid  poisoning.  Thus,  as  produced  by 
its  inhalation,  D.  R.  Brown45  noted  very  pronounced  cyanosis  of  the 
face  and  hands,  mental  confusion,  headache,  cold  extremities,  excessive 
muscular  weakness,  very  rapid,  feeble  pulse,  a  slow,  regular  respiration 
which  on  the  least  exertion  became  hurried  and  accompanied  by  a  pain- 
ful sense  of  oppression  in  the  chest  and  by  cardiac  distress.  When 
the  spirit  is  taken  by  the  mouth,  the  alcohol  in  it  asserts  its  physiological 
powers.  Thus,  in  a  child  three  years  old,  killed  in  twelve  hours  by  four 
ounces  of  the  spirit,  the  symptoms  closely  resembled  those  of  alcoholic 
poisoning,  with  the  addition  of  vomiting  and  purging.* 

The  therapeutic  dose  of  nitre  is  somewhat  calmative,  and  has  some  in- 
fluence, though  not  a  very  great  one,  in  increasing  the  secretions  of  the 
skin  and  kidneys.  It  is  a  very  popular  remedy,  especially  useful  in  the 
case  of  children  suffering  from  adynamic  fevers  with  such  nervous  symp- 
toms as  starting,  jerking,  mental  excitement,  etc.  If  the  patient  be  kept 
on  his  feet  and  cool  instead  of  being  warmly  covered  in  bed,  the  single 
large  dose  of  the  spirit  of  nitrous  ether  acts  as  a  mild  diuretic.  When  a 
diaphoretic  action  is  required,  small  doses  should  be  exhibited  at  short 
intervals.  Thus,  for  a  child  one  year  old  a  teaspoonful  may  be  put  in 
five  ounces  of  water  and  a  tablespoonful  be  given  every  half  to  one  hour. 
The  adult  dose  is  one  to  two  fluidrachms  (4-7  C.c. ). 

Spirit  of  Mindererus  (  LIQUOR  AMMONII  ACETATIS.  U.  S. — Solution 
of  Ammonium  Acetate}  is  a  colorless,  odorless  liquid,  prepared  by  satu- 
rating dilute  acetic  acid  with  ammonium  carbonate.  It  was  formerly 
used  to  a  considerable  extent  in  the  treatment  of  adynamic  fevers  as  a 
mild  stimulant  and  diaphoretic,  but  has  very  properly  fallen  into  disuse 
except  as  a  vehicle  for  more  powerful  remedies.  The  dose  usually  given 
is  one  to  two  tablespoonfuls  (7.5-15  C.c.),  but  two  ounces  (60  C.c.)  of 
it  may  be  exhibited  at  one  time. 

Before  the  introduction  of  jaborandi,  probably  the  most  useful  and 
most  efficient  known  diaphoretic  was  Dover's  Powder  (PuLVis  IPECACU- 
ANHAS ET  OPII,  U.  S. ),  which  contains  one  grain  of  opium,  one  grain 

*  Case,  Lancet,  1878,  ii.  Christison  reports  a  case  of  a  woman  whose  death  was 
attributed  to  sweet  spirit  of  nitre. 


DIAPHORETICS. 


729 


of  ipecacuanha,  and  eight  grains  of  sugar  of  milk.  When,  as  in  some 
cases  of  acute  rheumatism,  it  is  desired  at  the  same  time  to  allay  pain  and 
increase  the  action  of  the  skin,  Dover's  powder  may  be  exhibited  in  doses 
of  from  three  to  five  grains  (o.  2-0. 3  Gm. )  every  two,  three,  or  four 
hours,  pro  re  nata,  in  capsules  or  pill.  Given  in  a  single  large  dose, — ten 
grains  (0.7  Gm.),— especially  when  aided  by  proper  measures  and  other 
diaphoretics,  it  is  efficient  in  producing  a  free  perspiration,  and  may  thus 
be  used  in  forming  acute  colds,  etc.  In  the  intense  suffering  which  some- 
times results  from  sudden  suppression  of  menstruation,  Dover's  powder, 
by  relieving  pain  and  aiding  in  the  production  of  diaphoresis,  often  acts 
most  favorably. 


REFERENCES. 


DIAPHORETICS.  23 

1.  STEFFEN     .  .   .   .  Jahrb.f.  Kinderheilk.,  1871,  24. 

iii.  25. 

2.  BAELZ Verhandl.  d.  Congress,  f. 

innere  Med.,  1893.  26. 

3.  B.  M.  J.,  Oct.  1878.  27. 

4.  SCHOTTIN  ....  Arch.  f.    Physiol.    Heilk.,  28. 

1851,  xi.  29. 

5.  REES Encyclopaedia  of  Anat.,  iv. 

841-  30. 

6.  FIEDLER In.  Dis.,  Leipsic,  1854.  3I. 

7.  HIRSCHSPRUNG    .  Gaz.  des  H6p.,  1865.  32. 

8.  KAUP  and  JURGENSEN  .  D.  A.  K.  M.,  1869,  33. 

vi.  54-  34- 

9.  LEUBE D.  A.  K.  M.,  1869,  vii.  3.  35. 

10.  DEININGER    .  .  .  D.  A.  K.  M.,  1869,  vii.  587.  36. 

n.  FUNKE U.  N.  M.  T.,  vi.  37. 

12.  MEISSNER  ....  In  Dis.,  Leipsic,  1859.  38. 

13.  VULPIAN Lecons    sur    Subst.    Tox-  39. 

iques,  Paris,  1881,  87.  40. 

14.  HARDY  and  BALL  .  J.  de  Th.,  1874.  .  41. 

15.  PILICIER Med.  Centralb.,  1876,  430.  42. 

16.  MORAT Lyon  M.,  July,  1882. 

17.  PETTIT C.  R.  S.  B.,  1896,  iii.  43. 

18.  GOTTLIEB  .  .   .   .  A.  E.  P.  P.,  1894,  xxxiii.  261. 

19.  FEREOL J.  de  Th.,  Jan.  1875.  44. 

20.  LANGLEY    ....  J.  P.,  1878,  339. 

21.  CARVILLE  .  .  .  .  J.  de  Th.,  1875.  45. 

22.  SCHWANN  ....  Med.  Centralb.,  1875,  440.  46. 


FUCHSINGER  .  .  .  A.  G.  P.,  xv.  482. 
PRENTISS  .  .  .  .  P.  M.  T.,  xi.  610. 
RASORI Trans.  Internal.  Med. 

Cong.,  1881,  iii.  146. 

GROCCO L.  M.  R.,  1882, 137. 

LANGLEY    .  .   .   .  J.  A.  P.,  x.  188. 
LEYDEN  .  .   .  .     B.  K.  W.,  1877,  406. 
KAHLER  and  SAYKA  .  Med.  Centralb.,  1876, 

541- 

HARNACK  and  MEYER  .  A.  E.  P.  P.,  xii. 
HARNACK   ....  A.  E.  P.  P.,  xx. 
REICHERT  .   .  .   .  U.  M.  M.,  1893. 

RINGER Pract.,  xxvi.  12. 

MORAT  and  DOYON  .  C.  R.  S.  B.,  1892,  iv. 
LARVAND    ....  La  Pilocarpine,  1883. 
SCHANTA    .  .  .  .  W.  M.  W.,  1878,  No.  18. 
MURRELL   .   .   .   .  P.  J.  and  Tr.,  vi.  228. 

RINGER Pract.,  xvii.  401. 

CORNEVIN  .   .   .   .  C.  R.  S.  B.,  1891,  iii. 
LANGLEY    .   .   .   .  B.  M.  J.,  Feb.  1875. 

L.  L.,  1876,  i.  346. 
PURJESZ Pest.    Med.-Chir.    Presse, 

1880. 
JUHASZ Klin.  Monatsbl.  f.  Augen- 

heilk.,  xx.  86. 
HOFFERTS  ....  Wien.   Med.   Presse,  1883, 

xxiv.  1412. 

BROWN P.  J.  Tr.,  March,  1857. 

VOIT Z.  B.,  1902-03,  xliv. 


FAMILY   VI.— EXPECTORANTS. 


UNDER  the  present  heading  we  propose  to  discuss  not  only  true  ex- 
pectorants,— that  is,  those  medicines  which  have  the  power  of  influencing 
diseased  conditions  of  the  respiratory  mucous  membranes, — but  also  vari- 
ous substances  and  even  various  procedures  which  are  employed  for  the 
relief  of  pulmonic  conditions. 

Cough. — When  from  disease  or  from  other  causes  obnoxious  materials, 
be  they  secretions  or  foreign  matters,  accumulate  in  the  bronchial  tubes, 
cough  is  necessary  for  their  expulsion,  so  that  in  a  large  proportion  of 
cases  no  treatment  of  cough  is  desirable.  On  the  other  hand,  there  are 
cases  in  which,  owing  to  excessive  irritability  of  the  pulmonic  mucous 
membrane,  the  amount  of  cough  is  out  of  all  proportion  to  the  amount 
of  material  to  be  expelled.  Under  these  circumstances  the  symptom  is 
not  only  annoying,  but  also,  by  irritating  the  mucous  membrane  of  the 
lungs  and  by  exhausting  the  patient,  directly  harmful.  In  another  set  of 
cases,  owing  to  muscular  weakness  and  to  lack  of  irritability  of  the 
mucous  membrane,  the  cough  is  not  sufficient  for  the  expelling  of  the 
secretions,  which  gradually  accumulate  in  the  lungs,  fill  up  the  bronchial 
tubes,  and  finally,  it  may  be,  cause  death  by  a  process  comparable  to  that 
of  drowning. 

It  is  plain  that  the  medical  practitioner  must  study  in  each  individual 
case  the  relations  between  the  cough  and  the  amount  of  work  required  ; 
so  that  if  the  cough  be  excessive  it  may  be  allayed,  if  it  be  insufficient  it 
may  be  stimulated.  For  the  purpose  of  allaying  cough,  soothing  vapors 
or  liquids  may  be  applied  to  the  respiratory  mucous  membrane  by  inhala- 
tions, but  in  the  majority  of  cases  internal  anodynes  are  necessary. 

In  some  instances  the  cough  is  maintained  by  an  excessive  irritability 
in  the  upper  throat  and  air-passages,  so  that  demulcents  such  as  liquorice 
are  very  useful,  or  relief  may  be  obtained  by  sipping  a  mixture  composed 
of  glycerin  and  whiskey,  each  one  part,  with  two  to  four  parts  of  water. 

The  anodyne  substances  which  are  employed  for  the  relief  of  cough 
are  hydrocyanic  acid,  belladonna,  hyoscyamus,  chloroform,  the  bro- 
mides, and  heroine.  The  action  of  hydrocyanic  acid  is  too  brief  for  the 
remedy  to  be  of  practical  value.  Belladonna,  unless  locally  applied  by 
means  of  atomization,  is  very  uncertain  in  its  action  and  of  entirely  sec- 
ondary importance  ;  superior  to  it  is  hyoscyamus,  although  even  full 
doses  of  this  remedy  often  are  ineffective.  Chloroform,  in  doses  of  ten  to 
fifteen  minims,  sometimes  acts  most  happily,  but  must  be  given  at  very 


EXPECTORANTS.  73i 

short  intervals  on  account  of  the  fugaciousness  of  its  influence,  and  is 
more  useful  in  combination  than  alone.  The  bromides  in  full  doses  are 
often  effective,  and  may  well  be  combined  with  chloroform  ;  in  some 
cases  they  are  too  depressant.  Much  more  certain  in  its  influence  than 
any  remedy  yet  mentioned  is  opium  ;  its  tendency  to  check  secretion 
forbids  its  use,  however,  in  a  very  large  proportion  of  cases,  notably  in 
those  in  which  there  is  persistent  dryness  of  the  bronchial  mucous  mem- 
brane, whether  this  dryness  represents  the  first  stage  of  an  acute  bronchi- 
tis or  whether  the  case  be  one  of  a  continuing  subacute  bronchial  irritation 
so  frequent  in  neurotic  individuals.  Moreover,  the  usefulness  of  opiates 
is  further  limited  by  their  tendency  to  derange  digestion,  and  in  chronic 
cases  by  the  danger  of  forming  the  opium  habit.  Under  these  circum- 
stances the  diacetic  ester  of  morphine  (heroine)  is  very  valuable. 

We  know  of  no  method  of  increasing  the  irritability  of  the  pul- 
monic  mucous  membrane  when  impaired.  In  such  cases,  if  the  loss  of 
irritability  be,  as  it  usually  is,  dependent  on  general  atony,  strychnine 
and  cocaine  may  be  administered  in  full  doses,  and  are  sometimes  very 
serviceable.  In  an  acute  case,  with  failure  to  expel  the  secretion,  as  in 
the  suffocative  catarrh  of  infants,  life  may  sometimes  be  saved  by  me- 
chanical treatment.  Stimulating  emetics  are  often  of  the  greatest  service 
in  freeing  the  bronchial  tubes  of  secretion.  On  various  occasions  we  have 
resuscitated  young  children  after  they  had  become  completely  coma- 
tose and  lost  the  ability  of  swallowing  from  asphyxia  due  to  suffocative 
catarrh,  by  the  following  procedure,  which  was  suggested  to  us  by  the 
well-known  reflex  spasmodic  contraction  of  the  respiratory  muscles  pro- 
duced by  a  dash  of  cold  water  on  the  chest : 

Provide  three  tubs,  one  empty,  one  containing  ice-water,  and  one  with  water  at 
about  115°  F.  Hold  the  naked  body  of  the  child  over  the  empty  tub,  and  dash  over 
the  upper  thorax  a  ladleful  of  the  hot  water,  followed  immediately  by  one  of  the 
cold  water.  So  soon  as  the  color  of  the  skin  has  begun  to  change  under  the  respira- 
tory gaspings,  and  some  evidences  of  consciousness  appear,  dip  the  body  of  the 
child  momentarily  in  the  hot  water,  when  the  scream  produced  by  the  pain  will 
usually  fill  the  lungs  with  air.  In  this  procedure  the  hot  water  is  used  alternately 
with  the  cold  water  to  prevent  chilling  of  the  body  as  well  as  to  increase  the  shock. 

To  allay  Spasm. — When  a  spasm  affects  the  laryngeal  muscles 
acutely  it  may  often  be  put  an  end  to  by  an  emetic  dose  of  ipecacu- 
anha or,  in  a  very  robust  subject,  of  lobelia  ;  but  in  some  cases,  espe- 
cially in  so-called  laryngismus  stridulus,  the  exhibition  of  an  anaesthetic 
may  be  necessary  for  the  saving  of  life.  In  such  cases  chloroform  should 
be  selected  on  account  of  the  locally  irritating  influence  of  ether.  Amyl 
nitrite  in  alarming  cases  often  acts  most  happily.  For  the  prevention 
of  the  recurrence  of  these  spasms  the  various  anodynes  mentioned  above 
may  be  employed.  The  most  generally  successful  is  the  bromide,  which 
in  spasmodic  croup  should  be  given  repeatedly  in  full  doses.  Local  appli- 
cations of  belladonna — the  smoking  of  belladonna  cigarettes — are  often 
very  useful. 


732  LOCAL    REMEDIES. 

In  extreme  cases  of  asthmatic  bronchial  spasm  relaxation  may  be  ob- 
tained by  the  exhibition,  in  robust  cases,  of  lobelia  in  full  doses,  by 
smoking  belladonna  or  stramonium  cigarettes  or  pipes,*  by  the  inhala- 
tion of  amyl  nitrite  or  chloroform,  or  by  hypodermic  injections  of  mor- 
phine or  of  heroine  hydrochlorate. 

Local  applications  may  be  made  to  the  lungs  in  the  form  of  vapor  or 
of  fine  spray  obtained  by  the  so-called  pulverization  of  water. 

Atomization  consists  in  breaking  up  by  a  mechanical  contrivance 
watery  solutions  of  a  medicinal  substance  into  a  fine  spray.  At  one  time 
it  was  believed  that  in  this  way  the  finest  ramifications  of  the  bronchial 
tubes  could  be  reached,  but  the  method  has  gradually  passed  out  of  use 
except  for  cases  in  which  the  disease  is  in  the  fauces,  larynx,  or  trachea. 
In  using  atomization  it  must  be  remembered  that  it  is  only  a  means  of 
making  a  local  application  to  a  certain  part,  so  that  the  rules  governing 
the  choice  of  drugs  to  be  employed  are  precisely  those  affecting  local 
applications  to  other  than  the  respiratory  mucous  membrane. 

By  atomization  warm  water  may  be  applied  as  a  diluent  and  as  a 
soothing  application,  its  soothing  properties  being  capable  of  increase  by 
the  addition  of  cocaine,  opiates,  or  other  narcotic  remedies.  By  atomi- 
zation stimulant  substances,  such  as  ammonium  chloride,  also  benzoates, 
carbolates,  or  other  antiseptics,  may  be  brought  in  contact  with  a  dis- 
eased mucous  membrane.  When  there  is  excessive  secretion,  as  in  bron- 
chorrhoea,  or  hemorrhage,  as  in  haemoptysis,  the  practitioner  may  use  in 
the  atomizer  such  astringents  and  haemostatics  as — tannic  acid,  one  to 
twenty  grains  to  the  fluidounce  ;  alum,  from  five  grains  to  the  fluidounce 
to  a  saturated  solution  ;  iron,  Monsel's  solution,  five  to  fifteen  drops  to 
the  fluidounce.  In  all  cases  in  which  strong  local  applications  are  being 
made  to  the  lungs  the  occurrence  of  severe  cough  is  an  indication  that 
the  application  is  causing  much  irritation. 

TRUE    EXPECTORANTS. 

From  a  therapeutic  point  of  view  acute  bronchitis  is  divisible  into 
three  stages  :  first,  that  of  extreme  dryness  of  the  mucous  membrane 
and  tightness  of  cough  ;  second,  that  in  which  secretion  is  about  to  be 
established  ;  third,  the  final  stage,  in  which  expectoration  is  free.  In  an 

*  There  are  upon  the  markets  numerous  proprietary  mixtures  for  the  relief  of 
asthma  by  smoking ;  most  if  not  all  of  them  consist  of  powdered  belladonna  or  stramo- 
nium, mixed  with  potassium  nitrate  and  sometimes  other  substances.  Clinical  expe- 
rience has  shown  that  the  efficiency  of  these  powders  is  increased  by  the  presence  of 
arsenic,  which  probably  acts  by  stimulating  the  bronchial  mucous  membrane  to  secrete 
freely.  The  following  formula,  taken  from  an  old  Pharmacopoeia  of  the  Philadelphia 
Hospital,  we  have  found  to  yield  a  very  efficacious  paper. 

CHARTA  ARSENICALIS  COMPOSITA  (Compound  Arsenical  Paper).  R— Belladonnae 
fol.,  gr.  xcvi ;  Hyoscyami  fol.,  Stramonii  fol.,  aa  gr.  xlviii ;  Extr.  opii,  gr.  iv;  Tabaci,  gr. 
Ixxx  ;  Aquae,  Oj ;  M.,  ft.  sol.  et  add.  Potas.  nit.,  gr.  clx  ;  Potas.  arsenit.,  gr.  cccxx.  Satu- 
rate bibulous  paper  and  dry  for  use.  Roll  the  paper  into  cigarettes,  one  of  which  is  to  be 
smoked  two  to  six  times  a  day  until  relief  is  afforded  or  some  giddiness  is  produced. 


EXPECTORANTS.  733 

exacerbation  of  chronic  bronchitis  either  one  of  these  stages  may  be  rep- 
resented, but  in  a  continuing  course  of  the  chronic  bronchitis  there  is 
usually  a  condition  of  the  mucous  membrane  which  requires  the  use  of 
such  expectorants  as  are  employed  only  in  the  most  advanced  stages  of 
an  acute  bronchitis, — i.e. ,  of  a  stimulating  expectorant. 

In  accordance  with  the  division  just  made  of  the  stages  of  a  bron- 
chitis, expectorants  may  be  arranged  in  three  groups  :  first,  sedative  ex- 
pectorants ;  second,  expectorants  which  are  suitable  for  the  second  stage 
of  bronchitis,  which  may  be  termed  simply,  expectorants  ;  third,  stim- 
ulating expectorants. 

Of  course,  it  must  be  understood  that  the  division  which  has  been 
made  is  arbitrary,  and  that  very  frequently  there  are  conditions  in  which 
expectorants  of  one  group  may  well  be  combined  in  one  prescription 
with  those  of  another  group.  Thus,  ipecacuanha  and  ammonium  chlo- 
ride are  often  very  serviceable  in  union. 


EXPECTORANTS   OF   THE   FIRST   GROUP. 

The  sedative  expectorants  among  which  we  have  choice  in  the  first 
stages  of  a  bronchitis  are  lobelia,  tartar  emetic,  ipecacuanha,  potassium 
citrate,  and  apomorphine. 

Of  these  substances  Lobelia  is  to  be  employed  only  in  asthmatic  cases 
in  which  there  is  distinct  tendency  to  spasm  of  the  bronchial  tubes.  The 
tincture  (TiNCTURA  LOBELIA,  U.  S. )  may  be  given  in  doses  of  fifteen  to 
twenty  drops  (1-1.2  C.c. )  every  three  hours,  or  when  a  spasm  amounts 
to  a  violent  asthma,  one  fluidrachm  (3.7  C.c.)  may  be  exhibited  every 
two  hours  until  vomiting  is  produced.  When  large  doses  of  lobelia  are 
given  the  patient  must  be  closely  watched,  as  sometimes  an  alarming  de- 
pression is  produced. 

Tartar  Emetic  is  similar  in  its  expectorant  influence  to  ipecacuanha, 
but  much  more  powerful  and  much  less  safe.  It  should  never  be  used  in 
adynamic  cases  or  with  young  children.  Dose,  as  an  expectorant,  one- 
twelfth  to  one-sixth  of  a  grain  (0.005-0.01  Gm.),  repeated  according  to 
circumstances. 

ipecacuanha  is  very  largely  used  in  the  early  stages  of  acute  bron- 
chitis, and  is  the  safest  of  the  nauseating  expectorants.  The  dose  of 
the  syrup  is  from  thirty  drops  to  a  teaspoonful  (1.8-3.7  C.c.)  every 
two  to  four  hours,  according  to  the  exigencies  of  the  case. 

Potassium  Citrate,  when  given  in  large  doses,  has  a  very  notable  effect 
in  increasing  bronchial  secretion  during  the  dry  stage  of  a  bronchitis,  and 
especially  lends  itself  under  these  circumstances  to  combination  with 
ipecacuanha,  or  in  very  robust  cases  with  tartar  emetic  ;  one  ounce  (30 
Gm. )  of  it  should  be  given  in  the  twenty-four  hours.  For  many  patients 
its  taste  is  well  concealed  by  lemon-juice. 

Apomorphine  Hydrochlorate  is  a  valuable  sedative  expectorant,  useful 
in  exactly  the  class  of  cases  in  which  ipecacuanha  is  commonly  given. 


734  LOCAL    REMEDIES. 

The  expectorant  dose  is  one-twelfth  of  a  grain  (0.005  Gm.),  repeated 
every  two  or  three  hours. 

EXPECTORANTS   OF   THE   SECOND   GROUP. 

AMMONII    CHLORIDUM— AMMONIUM    CHLORIDE.     U.  S. 

Ammonium  Chloride  occurs  in  large  concavo-convex  plates,  white, 
translucent,  tough  and  fibrous,  free  from  odor,  but  having  a  sharp,  saline 
taste,  and  soluble  in  three  parts  of  cold  and  one  part  of  boiling  water. 

THERAPEUTICS. — Ammonium  chloride  is  a  powerful  irritant,  concern- 
ing whose  poisonous  properties  there  is  great  diversity  of  statements. 
Oesterlen  affirms  that  he  has  seen  two  ounces  of  the  salt  taken  by  man 
without  the  production  of  more  serious  results  than  violent  gastro-intes- 
tinal  pain  and  diarrhoea,  whilst  older  observers  state  that  two  drachms  of 
the  salt  are  sufficient  to  cause  death  in  a  dog.  According  to  Arnold, 
thirty  grains  will  kill  a  rabbit  in  ten  minutes  ;  but  Rabuteau  found 
that  one  drachm  injected  intravenously  produced  in  the  dog  only 
vomiting,  muscular  weakness,  temporary  paralysis  of  the  hind  legs,  and 
general  prostration,  lasting  four  or  five  hours.  After  absorption  it  shares 
the  general  physiological  activity  of  the  ammoniacal  salts.  When  given 
for  a  length  of  time  in  very  large  doses  it  affects  the  general  nutrition. 
We  have  seen  extreme  prostration  and  a  typhoid  condition  apparently 
produced  by  the  taking  of  half  an  ounce  per  diem  for  some  days, 
whilst  great  prostration,  with  an  eruption  of  bloody  blebs,  haematuria, 
and  hemorrhages  from  the  mucous  membranes,  has  been  reported  by 
Isham  as  caused  by  the  continuous  use  of  the  drug. 

These  symptoms  are  concordant  with  the  statements  of  Sundelin,  that 
the  blood  suffers  especially  and  loses  its  plasticity  under  the  action  of  the 
drug.  In  an  elaborate  series  of  analyses,  F.  W.  Bocker1  determined 
that  its  long  use  is  accompanied  by  a  decided  decrease  in  the  solids  of  the 
blood, — an  observation  confirmed  by  Arnold.  Both  Bocker  and  Rabu- 
teau 2  found  that  in  healthy  man  it  notably  increases  the  urea  and  other 
solids  of  the  urine  except  uric  acid,  so  that  when  taken  in  large  amount 
and  continuously  it  evidently  has  a  positive  influence  on  the  chemical 
movements  of  the  organism. 

According  to  Rabuteau,  ammonium  chloride  is  freely  secreted  by  the 
salivary  glands,  but  chiefly  escapes  from  the  kidneys,  almost  all  the  salt 
taken  being  recoverable  from  the  urine. 

Although  there  is  sufficient  reason  for  believing  that  ammonium 
chloride  especially  affects  the  respiratory  mucous  membrane,  the  state- 
ment of  Bocker,  that  it  hastens  very  greatly  the  nutritive  changes  and 
the  exfoliation  of  the  epithelium  in  all  mucous  membranes,  is  in  accord 
with  clinical  experience  as  to  its  value  in  various  gastro-intestinal  condi- 
tions. In  Germany  more  than  in  this  country  it  has  been  extensively 
used  in  the  treatment  of  chronic  gastric  and  intestinal  catarrhs.  The 
statement  of  W.  Stewart,8  made  in  1870,  that  it  is  an  effective  remedy 


EXPECTORANTS.  7« 

/  O*J 

in  chronic  torpor  of  the  liver  and  chronic  hepatitis,  has  been  sustained 
by  subsequent  clinical  experience,  and  it  has  become  a  standard  remedy 
in  these  affections  and  in  catarrhal  jaundice.  As  an  expectorant  ammo- 
nium chloride  is  useful  in  an  aczitc  bronchitis  when  free  secretion  has 
just  been  established.  In  chronic  bronchitis  it  should  be  administered 
from  time  to  time  when  the  secretion  is  not  very  free. 

Ammonium  chloride  was  at  one  time  frequently  given  in  intermittent 
fever,  but  has  failed  to  sustain  itself.  Another  old  use  was  for  relieving 
pain  in  neuralgia,  especially  of  the  ovarian  variety.  Thirty  grains  of  it 
were  administered  in  combination  with  two  to  five  drops  of  tincture  of 
aconite  root,  repeated  in  half  an  hour  if  necessary.  In  our  hands  this 
treatment  has  not  given  satisfaction.  The  expectorant  dose  of  ammo- 
nium chloride  is  five  to  ten  grains  (0.3-0.6  Gm. )  every  three  hours,  in 
at  least  two  ounces  of  water.  The  dose  in  hepatic  diseases  is  twenty  to 
thirty  grains  (1.3-2  Gm. )  in  four  or  five  ounces  of  water,  three  or  four 
times  a  day,  administered  when  the  stomach  is  empty. 

EXPECTORANTS   OF   THE   THIRD   GROUP. 

GRINDELIA.     U.S. 

This  is  the  leaves  and  flowering  tops  of  Grindelia  robusta  and  of 
Grindelia  squarrosa,  plants  inhabiting  the  extreme  western  portions  of 
North  America.  In  commerce  the  whole  herb,  including  the  stems, 
roots,  and  floral  heads,  is  sold.  The  taste  is  warmish,  peculiar,  and  very 
persistent.*  The  presence  of  a  crystalline  alkaloid  in  grindelia  has  been 
asserted  by  several  investigators,  but  at  present  it  seems  probable  that 
its  activity  depends  upon  a  turpentine-like  volatile  oil. 

PHYSIOLOGICAL  ACTION. — The  toxic  powers  of  grindelia  are  said  to 
be  so  feeble  that  three  drachms  of  the  fluid  extract  are  required  to  kill 
a  rabbit.  Concerning  its  physiological  action  we  have  little  definite 
knowledge  ;  according  to  Buffington,  it  produces  narcosis  with  dilated 
pupils  by  a  cerebral  influence,  but  acts  more  powerfully  in  paralyzing  the 
nerves  of  sensation  and  the  sensory  side  of  the  cord,  and  finally  attacks 
both  the  motor  cord  and  nerves.  Dobroklowski  asserts  that  it  acts  upon 
the  motor  nerves  and  the  muscles.  Buffington  affirms  that  it  causes  in 
warm-blooded  animals  a  slowing  of  the  action  of  the  heart  by  stimu- 
lating the  inhibitory  apparatus,  and  an  elevation  of  the  blood-pressure 
by  stimulating  the  vaso-motor  centres.  Dobroklowski  states  that  the 
large  but  non-toxic  doses  increase  the  pulse-rate  as  well  as  the  arte- 
rial tension  ;  also  that  these  phenomena  not  being  affected  either  by 
isolation  of  the  heart  from  the  nervous  system,  by  the  previous  use 
of  atropine,  or  by  division  of  the  spinal  cord,  they  must  be  caused 
by  a  direct  influence  upon  the  heart  or  the  peripheral  vessels.  Do- 
broklowski further  affirms  that  in  toxic  dose  the  drug  depresses  the 

*  See  Centralbl.f.  Med.  Wissens.,  1885,  xxiii. ;  Amer.  Journ.  Med.  Set.,  Jan.  18, 1886; 
Land.  Med.  Rec.,  March,  1886. 


736  LOCAL    REMEDIES. 

pulse-rate    and    the    arterial   tension,   and    finally  arrests    the    heart   in 
diastole. 

THERAPEUTICS. — Grindelia  has  not  been  employed  for  its  effect  upon 
the  circulation,  and  in  the  doses  used  in  medicine  it  appears  to  exert  no 
distinct  influence  upon  the  heart  or  arteries.  It  has  been  largely  used, 
often  with  alleged  excellent  results,  in  asthma,  and  in  bronchitis  associ- 
ated with  a  tendency  to  bronchial  spasm.  It  is  probable  that  in  these 
cases  it  not  only  has  a  relaxing  influence,  but  also  stimulates  the  mucous 
membrane,  and  even  in  chronic  bronchitis,  especially  of  the  aged,  it 
is  said  to  do  good.  It  has  been  employed  in  w hooping -cough.  Its 
active  principles  are  probably  excreted  by  the  kidneys  ;  hence  after 
large  doses  there  are  sometimes  evidences  of  renal  irritation,  and  in 
chronic  catarrh  of  the  bladder  good  has  been  effected  by  its  stimulant 
influence  upon  the  mucous  membranes  of  the  viscus.  It  has  also  been 
employed  as  a  local  application,  with  alleged  good  results,  in  vaginitis. 
The  dose  of  the  fluid  extract  (FLUIDEXTRACTUM  GRINDELI^E,  U.  S. ) 
is  from  twenty  to  sixty  minims  (1.2—3.7  C.c. ).  The  fumes  of  burning 
grindelia  are  sometimes  inhaled  with  alleged  relief  in  asthma.  The  plant 
should  be  steeped  in  a  solution  of  nitre,  dried,  and  burnt  upon  a  plate,  or 
may  be  smoked  in  cigarettes  or  in  a  pipe. 

BALSAMUM  PERUVIANUM,  U.  S. ,  Balsam  of  Peru,  is  obtained  from 
Toluifera  Pereirae,  a  tree  of  Central  America.  This  balsam  is  a  viscid, 
honey-like,  fragrant,  brownish  fluid,  of  a  warm,  bitterish  taste,  which  has 
been  shown  by  Brautigam  and  Nowack 4  to  be  practically  devoid  of  anti- 
septic properties.  According  to  Fre"my,  it  contains  not  benzoic,  but  cin- 
namic  acid.  It  has  been  used  in  chronic  catarrhs  of  the  respiratory  and 
the  genito-urinary  systems,  in  doses  of  half  a  fluidrachm  (2  C.c.). 

BALSAMUM  TOLUTANUM,  U.  S. ,  Balsam  of  Tolu,  is  obtained  from 
Toluifera  Balsamum,  a  tree  very  closely  allied  to  that  which  yields  the 
balsam  of  Peru.  Balsam  of  Tolu  is  at  first  a  thick,  viscid  fluid,  but  by 
time  it  is  converted  into  a  hard,  translucent,  resinous  solid.  Its  odor  is 
highly  fragrant  and  its  taste  vanilla-like.  It  contains  cinnamic  acid  and 
a  volatile  oil,  and  its  medical  properties  are  the  same  as  those  of  the  balsam 
of  Peru.  On  account,  however,  of  its  grateful  taste,  it  is  preferred  to  the 
latter,  and  is  very  much  used  to  flavor  medicines,  especially  cough-mix- 
tures. In  large  doses,  twenty  to  thirty  grains  (1.3—2  Gm. )  every  three 
hours,  it  may  be  of  some  value  in  chronic  bronchitis,  but  as  generally 
used  its  preparations  are  simply  agreeable  vehicles.  The  dose  of  the 
tincture  (TINCTURA  TOLUTANA — twenty  per  cent. ,  U.  S. )  is  one-half  to 
one  fluidrachm  (2-4  C.c.);  of  the  much  more  frequently  used  syrup 
(SYRUPUS  TOLUTANUS,  U.  S. ),  half  a  fluidounce  (15  C.c.). 

ALLIUM,   or  English    Garlic,    the   clove   of  Allium   sativum,    con- 
tains a  volatile  oil  which  in  small  doses  is  a  stimulant  to  digestion,  and 


EXPECTORANTS.  737 

is  also  used  as  a  stimulating  expectorant  in  the  advanced  stages  of  obsti- 
nate bronchitis,  and  in  the  acute  bronchitis  of  infants,  when  the  powers  of 
the  system  begin  to  flag.  The  oil  of  garlic  is  further  believed  to  have  the 
ability  to  stimulate  the  expulsive  function  of  the  small  bronchial  tubes, 
and  is  certainly  a  powerful  rubefacient  and  a  decided  nervous  stimulant. 
For  these  reasons,  garlic  poultices  are  a  favorite  application  in  the  acute 
suffocative  catarrh  of  infants,  and  are  not  rarely  applied  to  the  spine,  legs, 
and  feet  in  general  infantile  convulsions.  They  are  made  by  simply  re- 
ducing the  garlic  to  a  pulp  by  pounding.  When  a  continuous  applica- 
tion is  desirable  to  the  delicate  skin  of  an  infant,  as  in  catarrh,  it  is 
generally  necessary  to  reduce  their  strength  with  flaxseed  meal.  The 
dose  of  the  syrup  (SYRUPUS  ALLII,  U.  S.  1890)  for  a  child  a  year  old  is 
one  fluidrachm  (4  C.c.). 

SCILLA,  U.  S.,  or  Squill,  is  one  of  the  most  used  of  the  stimulating 
expectorants,  coming  especially  into  play  in  the  advanced  stages  of 
ordinary  bronchitis.  The  syrup  (SYRUPUS  SCILL^E,  U.  S. )  is  the  favor- 
ite expectorant  preparation.  As  it  contains  acetic  acid,  it  is  incompati- 
ble with  ammonium  carbonate.  Compound  Syrup  of  Squill,  or  Coxe's 
Hive  Syrup  ( SYRUPUS  SCILL^E  COMPOSITUS,  U.  S.),  contains  one  grain 
of  tartar  emetic  to  the  ounce,  and  is  therefore  sedative  to  the  circulation, 
although  stimulant  to  the  bronchial  mucous  membrane.  It  is  not  suit- 
able for  young  children,  although  it  has  been  much  used  in  spasmodic 
croup.  The  dose  of  the  simple  syrup  is  one-half  to  one  fluidrachm  (2—4 
C.c. )  ;  of  the  compound,  twenty  to  forty  drops  ( i.  2— 2.5  C.c. ),  according 
to  age,  repeated  every  twenty  minutes  until  it  operates. 

Pix  LIQUIDA.  U.  S. —  Tar  is  a  black  semi-liquid  substance,  of  peculiar 
odor  and  taste,  obtained  by  the  destructive  distillation  of  various  species 
of  pine.  The  tar  used  in  this  country  is  almost  exclusively  the  product 
of  the  Pinus  palustris  of  North  Carolina  and  other  of  the  Southern 
States.  In  composition  it  is  very  complex,  containing  pyroligneous 
acid,  creosote,  empyreumatic  oil,  and  a  number  of  more  or  less  peculiar 
principles.  When  distilled,  it  yields  an  oily  liquid,  known  as  oil  of  tar, 
and  a  solid,  black  residue,  pitch.  It  is  freely  soluble  in  alcohol,  ether, 
and  the  fixed  and  volatile  oils,  and  also  to  a  slight  extent  in  water.  The 
physiological  action  of  tar  resembles  that  of  creosote.  According  to 
Taylor,  the  oil  of  tar  has  produced  death  in  man.  To  cause  death,  tar 
itself  would  have  to  be  ingested  in  enormous  quantity,  since  a  sailor 
(according  to  Still£)  recovered  after  taking  between  a  pint  and  a  quart 
of  it.  It  is  used  internally  solely  in  the  advanced  stages  of  obstinate 
acute  bronchitis,  or  in  chronic  bronchitis.  Locally,  it  is  much  employed 
in  chronic  diseases  of  the  skin,  as  a  stimulant  application  in  the  form  of 
the  official  ointment  (UxcuENTUM  PICIS  LIQUIDS,  U.  S., — equal  parts). 
In  many  cases  this  is  too  severe,  and  the  strength  must  be  reduced. 
Hebra  states  that  if  it  be  applied  too  freely  enough  of  the  tar  may  be  ab- 

47 


738  LOCAL    REMEDIES. 

sorbed  to  darken  the  color  of  the  faeces  and  the  urine,  and  even  to  cause 
gastric  irritation  and  black  vomit.  For  internal  administration  the  best 
preparation  is  the  Syrup  of  Tar  (SYRUPUS  PICIS  LIQUIDS — 7.5  per 
cent.,  U.  S.)  Dose,  one  to  two  fluidrachms  (3.7-7  C.c. ). 

TEREBENUM.  U.  S. —  Terebene  is  a  clear,  colorless  liquid,  insoluble 
in  water,  isomeric  with  turpentine,  and  of  a  peculiar  odor,  somewhat 
resembling  that  of  freshly  sawed  pine  wood.  It  is  prepared  by  the  action 
of  sulphuric  acid  upon  oil  of  turpentine. 

Terebene,  one  of  the  most  effective  of  the  stimulant  expectorants,  was 
first  recommended  by  William  Murrell.5  It  is  very  useful  not  only  in 
chronic  bronchitis,  but  also  in  the  acute  disease  after  the  earlier  stages  have 
passed  by.  As  an  expectorant  it  is  nearly  equivalent  to  the  oil  of  eucalyp- 
tus, but  is  more  stimulating.  It  has  also  been  employed  with  asserted  good 
results  in  dyspepsia,  especially  in  the  flatulent  intestinal  variety,  and  may 
be  used  in  chronic  or  subacute  inflammations  of  the  genito-urinary  tract. 
Its  action  upon  the  general  system  has  not  been  investigated,  but  proba- 
bly resembles  that  of  oil  of  turpentine.  From  twenty  to  forty  minims 
(1.2-2.5  C.c.)  of  it  may  be  given  to  the  adult  in  the  course  of  twenty- 
four  hours.  It  lends  itself  well  to  use  by  inhalations,  either  by  atomiza- 
tion  of  water  containing  it  or  by  vaporization  from  hot  water.  The  vapor 
should  be  as  concentrated  as  can  be  borne  without  exciting  cough. 

OLEUM  SANTALI,  U.  S.,  Oil  of  Sandal  Wood,  is  a  pale  yellowish, 
strongly  pungent,  aromatic,  and  spicy  volatile  oil,  obtained  from  the  wood 
of  the  Santalum  album.  It  is  a  stimulant  or  irritant  to  the  various  mu- 
cous membranes,  and  while  its  general  action  upon  the  system  is  not 
known,  it  is  a  very  valuable  remedy  in  chronic  bronchitis  and  in  the  ad- 
vanced stages  of  acute  bronchitis,  and  also  in  the  advanced  stages  of  gon- 
orrhcea.  It  seems  to  be  more  stimulating  than  is  the  oil  of  eucalyptus. 
From  ten  to  twenty  drops  ( i . 2-2. 5  C.c.)  may  be  given  every  three  or 
four  hours  in  capsules,  emulsions,  or  on  sugar. 

Among  the  most  valuable  of  the  stimulant  expectorants  are  the  oil  of 
eucalyptus  and  creosote.  ( See  pages  550  and  565. ) 

TERPIN  HYDRATE.  TERPINI  HYDRAS.  U.S. — This  substance,  which 
occurs  in  colorless,  nearly  odorless  prisms,  of  a  slightly  aromatic  and  some- 
what bitter  taste,  nearly  insoluble  in  water,  soluble  in  alcohol,  is  used  in 
practical  medicine  as  a  stimulant  expectorant,  resembling  in  its  action 
other  members  of  the  turpentine  group,  and  especially  useful  in  chronic 
bronchitis  and  in  the  advanced  stages  of  acute  bronchitis  when  the  secre- 
tion is  unusually  free.  In  our  experience  it  is  better  borne  by  the  stomach 
than  is  terebene,  and  is,  in  its  action  upon  the  lungs,  scarcely  distinguish- 
able from  that  agent.  It  has  also  been  used  in  chronic  cystitis,  and 
in  gonorrhoea.  It  may  be  given  in  doses  of  from  three  to  six  grains 
(0.2-0.4  Gm. )  four  to  six  times  a  day,  in  capsules. 


EXPECTORANTS.  739 

SAPONINE. — This  glucoside  is  very  widely  spread  throughout  the  veg- 
etable kingdom,  Robert T  giving  a  list  of  one  hundred  and  forty  plants  which 
contain  principles  of  the  saponine  class.  According  to  the  same  authority, 
chemically  pure  saponine  is  physiologically  inert,  but  saponine  of  com- 
merce is  a  very  active  poison,  and  all  of  the  plants  containing  it  in  con- 
siderable amount  are  capable  of  producing  symptoms  similar  to  those 
caused  by  commercial  saponine.  The  symptoms  caused  by  poisoning 
with  saponine  plants  are  violent  vomiting  and  purging,  the  result  of  an 
intense  gastro-irritation  ;  convulsions  ;  renal  irritation  ;  alterations  in  the 
blood  itself, — these  plants  being,  in  fact,  actively  toxic  to  all  forms  of 
protoplasm. 

Of  the  drugs  containing  saponine,  two  are  recognized  by  the  U.  S. 
Pharmacopoeia,  and,  to  some  extent,  used  in  practical  medicine. 

SENEGA.  U.  S. — The  root  of  the  indigenous  Polygala  senega — 
containing  saponine  (the  polygalic  acid  of  the  older  chemists)  and  a 
second  active  principle,  senegin — is  used  to  a  considerable  extent  in  the 
United  States  as  a  stimulating  expectorant  in  the  very  advanced  stages 
of  acute  bronchitis,  and  in  chronic  bronchitis  with  free  expectoration.  It 
is  really  of  little  value,  and  causes  in  full  dose  much  gastro-intestinal 
irritation.  Dose  of  the  fluid  extract  (FLUIDEXTRACTUM  SENEGA,  U.  S. ), 
ten  to  fifteen  drops  (0.6-1  C.c. );  of  the  syrup  (SYRUPUS  SENEGA, 
U.  S. ),  one  fluidrachm  (3.7  C.c.). 

QUILLAJA.  U.  S. — Soap-bark,  the  inner  bark  of  the  Chilean  tree,  is 
probably  the  most  actively  poisonous  of  all  the  saponine-containing  drugs. 
On  account  of  its  detergent  properties,  it  is  very  largely  used  in  the  arts 
for  cleansing  silk  and  other  fabrics.  It  is  also  employed  as  an  emulsi- 
fying agent  by  the  apothecaries,  but  its  active  physiological  properties 
forbid  such  use  of  it.  Robert  recommends  it  as  a  cheap  substitute  for 
senega,  given  to  the  adult  as  a  stimulating  expectorant,  a  tablespoonful 
of  a  two  and  a  half  per  cent,  decoction. 

There  are  a  number  of  expectorants  of  very  small  value,  but  requiring  notice 
on  account  of  their  being  in  use.  Ammoniac  (AMMONIACUM),  an  irritant  gum- 
resin,  was  formerly  used  to  a  considerable  extent  in  chronic  bronchitis  in  doses  of 
from  twenty  to  thirty  grains  (1.3-2  Gm.);  of  the  emulsion  (EMULSUM  AMMONIACI 
— four  per  cent.),  one  to  two  tablespoonfuls  may  be  given.  The  EMPLASTRUM 
AMMONIACI  CUM  HYDRARGYRO,  containing  sulphur,  has  been  employed  as  a 
local  alterative  and  discutient  in  scrofulous  swellings.  Horehound  (MARRUBIUM, 
U.  S. )  contains  a  volatile  oil  and  a  bitter  principle,  marrubiin  ;  also  tannin.  It  is 
used  domestically  to  a  considerable  extent  in  catarrhs  of  the  upper  respiratory  tract. 
Dose  of  the  powder,  thirty  grains  to  one  drachm  (2-4  Gm. ).  Bloodroot  (SAN- 
GUINARIA,  U.  S. )  is  in  overdoses  an  emetocathartic  and  narcotic  poison.  It  con- 
tains sanguinarine  and  other  alkaloids,  and  has  been  used  in  chronic  bronchitis,  but 
has  no  practical  value.  Dose  of  the  fluid  extract  (FLUIDEXTRACTUM  SANGUINARY, 
U.  S. ),  two  minims  (o.i  C.c.).  Sanguinarine  is  a  violent  poison,  causing  in  mam- 
mals vomiting,  purging,  collapse,  convulsions,  loss  of  reflex  activity,  cardiac 


740  LOCAL   REMEDIES. 

depression,  and  finally  death  from  asphyxia.     (For  details  see  eleventh  edition  of 
this  treatise. ) 

SULPHURETTED  HYDROGEN. — In  1886  Bergeon6  proposed  a  method  of  treating 
phthisis  by  filling  the  large  intestine  with  sulphuretted  hydrogen  diluted  with  pure 
carbonic  acid  gas.  After  an  extraordinary  but  very  brief  popularity  the  method  has 
fallen  into  such  complete  desuetude  that  it  is  only  necessary  here  to  refer  to  the 
tenth  edition  of  this  treatise  for  details. 

Sulphuretted  hydrogen  is,  however,  a  valuable  remedy  in  the  treatment  of 
purulent  pulmonic  catarrhs,  whether  of  tubercular  or  other  origin.  When,  under 
any  circumstances,  a  bronchial  catarrh  is  accompanied  by  very  free  expectoration 
the  remedy  may  be  useful  in  relieving  the  mucous  membrane.  We  have  also  found 
it  of  service  in  chronic  gout,  when  administered  persistently  for  months.  The 
method  of  administration  employed  by  Bergeon  was  barbarous  and  absurd.  The 
sulphuretted  hydrogen  may  be  given  by  the  mouth  in  the  form  of  a  natural  sulphur- 
water  or,  better,  by  means  of  water  saturated  with  sulphuretted  hydrogen  and  car- 
bonic acid  gas.  The  dose  of  the  saturated  solution  is  two  to  four  ounces  (60-118 
C.c. ),  three  or  four  times  a  day.  In  some  cases  it  produces  digestive  disturbance, 
and  its  use  has  to  be  abandoned.  That  the  gas  is  absorbed  and  eliminated  by  the 
lungs  is  proved  by  the  very  perceptible  odor  upon  the  breath.  Many  of  the  sulphur 
springs  of  Europe  have  inhaling  chambers,  and  experience  has  shown  that  the 
sulphurous  vapors  are  of  value. 


REFERENCES. 

EXPECTORANTS.  4.  BRAUTIGAM  and    NOWACK  .  C.  K.   M.,   1889, 

1.  BOCKER     Beitr.  z.  Heilk.,  ii.  170.  xxiv. 

2.  RABUTEAU    .   .   .   .  L'Union   M6d.,   1871,    xii.  5.  MURRELL B.  M.  J.,  Dec.  1885. 

329.  6.  BKRGEON C.  R.  A.  S.,  July,  1885. 

3.  STEWART Chloride   of    Ammonium,  7.  ROBERT Chem.  Centralblatt,    1893, 

Rangoon,  1870.  «.  i«. 


FAMILY   VII.— EMMENAGOGUES. 


EMMENAGOGUES  are  medicines  which  are  employed  to  promote  the 
menstrual  flux.  In  the  great  majority  of  cases  amenorrhoea  is  due  to 
some  local  pelvic  disease  or  general  constitutional  condition,  the  removal 
of  which  relieves  the  symptom.  There  are  a  few  substances  which 
appear  to  act  directly  as  stimulants  to  the  uterine  mucous  membrane, 
although  they  are  notoriously  uncertain  in  their  effectiveness. 

When  amenorrhoea  is  a  symptom  of  chlorosis  or  due  to  other  forms 
of  anaemia,  full  doses  of  iron  should  be  given.  With  iron  may  be  com- 
bined the  gum-resin  myrrh,  as  in  the  compound  mixture  of  iron  (Mis- 
TURA  FERRI  COMPOSITA,  U.  S. — Griffith's  Mixture}.  Dose,  from  one 
to  two  fluidrachms  (4-7  C.c. ),  three  times  a  day.  When  atonic  amenor- 
rhoea exists  with  constipation,  aloes  should  be  given  along  with  the  other 
emmenagogues.  Ordinarily  it  should  be  administered  in  repeated  doses 
(three  times  a  day)  of  such  size  as  will  produce  daily  one  or  two  soft, 
semi-liquid  stools.  At  the  menstrual  period  advantage  may  sometimes 
be  derived  from  the  administration  of  a  full  purgative  dose. 

POTASSIUM  PERMANGANATE,  originally  recommended  by  Sydney 
Ringer  as  an  emmenagogue,  has  been  very  highly  commended  by  For- 
dyce  Barker  and  other  physicians.*  According  to  Barker,  the  perman- 
ganate is  not  to  be  employed  when  menstruation  has  been  arrested  by 
grave  constitutional  or  local  disease,  or  suddenly  by  cold,  moral  shock, 
or  acute  disease.  Abortifacient  properties  have  been  attributed  to  it, 
and  cases  are  reported  in  which  abortion  has  followed  its  administra- 
tion, f 

Therapeutic  doses  of  the  permanganate  must  be  entirely  decomposed 
in  a  very  short  time  after  they  reach  the  stomach,  so  that  any  action 
which  the  drug  exerts  upon  the  general  system  is  due  to  the  manganese 
oxide  ;  indeed,  the  ordinary  black  manganese  oxide  has  been  affirmed 
by  various  practitioners  to  be  as  active  an  emmenagogue  as  is  the  per- 
manganate. We  have  employed  these  agents  to  a  limited  extent  in  func- 
tional amenorrhoea,  sometimes  with,  sometimes  without,  success.  The 
only  difference  which  we  have  been  able  to  perceive  in  their  action  is 
that  the  permanganate  is  the  more  irritant  to  the  stomach.  The  dose  of 
either  preparation  may  be  set  down  as  one  to  two  grains  (0.06-0. 13  Gm. ), 
— always  administered  after  meals,  in  order  to  avoid,  as  far  as  possible, 

*  See  Therap.  Gaz.,  ii.  and  iii. 

t  J.  L.  Watkins  (Therap.  Gaz.,  ii.),  and  S.  B.  Sperry  (Ibid.,  iii.). 

741 


742  LOCAL    REMEDIES. 

gastric  irritation.     Cases  of  severe  gastritis  produced  by  the  permanganate 
have  been  reported.1 

CANTHARIDES  is  a  very  decided  uterine  stimulant,  and  is  much  used 
in  emmenagogue  mixtures.  From  two  to  five  minims  (o.  13-0. 3  C.c. ) 
of  the  tincture  may  be  given  three  times  a  day  ;  if  no  unpleasant  symp- 
toms arise,  the  dose  may  cautiously  be  increased  to  six  minims,  the 
production  of  strangury  being,  of  course,  sedulously  avoided. 

GUAIAC,  as  an  emmenagogue,  is  much  less  stimulating  than  can- 
tharides,  and  is  believed  by  some  to  be  especially  useful  in  rheumatic 
dysmenorrhcea.  In  this  affection,  full  doses  of  the  ammoniated  tincture 
should  be  given.  The  following  formula,  adapted  from  that  of  Dewees, 
known  as  Dewees' s  Emmenagogue  Mixture,  is  probably  the  most  effec- 
tive combination  ever  made  in  atonic  amenorrhoea.  The  proportion  of 
the  various  ingredients  should  be  varied  to  suit  the  exigencies  of  indi- 
vidual cases. 

R  Tincturae  ferri  chloridi,  f 3 iii ;  Tincturae  cantharidis,  f^i ;  Tincturae  aloes, 
£555;  Tincturae  guaiaci  ammoniatae,  f^iss;  Syrupi,  q.  s.  ad  f,^vi.  S. — Table- 
spoonful  three  times  a  day. 

SABINA.  U.  S. — Savine. — The  dried  tops  of  Juniperus  sabina,  a 
juniper,  native  of  the  south  of  Europe  and  the  Levant,  contain  a  turpen- 
tine-like volatile  oil.  This  oil  is  a  powerful  irritant.  When  taken  in 
sufficient  dose,  it  produces  severe  abdominal  pain  ;  incessant  vomiting 
and  bloody  purging  ;  diminution  or  even  suppression  of  the  urine,  which 
is  often  albuminous  and  bloody  ;  disordered  respiration  ;  symptoms  of 
disturbed  innervation,  such  as  unconsciousness,  stertorous  breathing,  and 
convulsions  or  convulsive  tremblings  ;  the  scene  closing  by  death  in 
collapse.  In  pregnant  females,  abortion,  accompanied  by  violent  flood- 
ing, almost  always  occurs  before  the  fatal  issue.  After  death,  signs  of 
gastro- intestinal  inflammation  are  generally  present,  but  in  some  in- 
stances these  are  wanting,  and  in  one  case  reported  by  Letheby  *  pul- 
monary apoplexy  and  congestion  of  the  brain  were  the  chief  lesions. 

In  rare  cases  of  menorrhagia  dependent  upon  uterine  relaxation,  the 
oil  of  savine  is  useful  in  doses  of  from  five  to  ten  drops  (0.3-0.6  C.c.).. 
It  owes  its  importance  to  the  frequency  of  its  domestic  use  as  an  aborti- 
facient, — a  use  which  is  accompanied  by  the  gravest  danger  to  life  and 
has  often  ended  in  death.  The  dose  of  the  volatile  oil  (OLEUM  SABIN^E, 
U.  S. )  is  from  three  to  five  minims  (0.2-0.3  C.c.);  of  the  fluid  extract 
(FLUIDEXTRACTUM  SABIN^E,  U.  S. ),  ten  to  twenty  minims  (0.6-1.2  C.c. ). 

RUE. — The  leaves  of  Ruta  graveolens,  or  common  garden  rue,  contain 
a  volatile  oil  whose  properties  are  similar  to  those  of  oil  of  savine.  It  has 
been  used  in  Europe  for  the  production  of  criminal  abortion,  but  seems 
to  be  less  employed  than  is  the  oil  of  savine,  and  to  be  less  dangerous, 


EMMENAGOGUES.  743 

as  we  have  met  with  no  records  of  death  from  it  except  that  of  a  man 
weakened  by  dysentery.*  According  to  M.  Helie,  taken  internally,  in 
large  doses,  it  causes  violent  gastric  pains,  excessive  and  sometimes 
bloody  vomiting,  profuse  salivation  and  swelling  of  the  tongue,  great 
prostration,  confusion  of  mind,  and  convulsive  twitchings,  with,  in  preg- 
nant women,  abortion. 

TANACETUM. — The  common  tansy  of  the  gardens,  Tanacetum  vul- 
gare,  in  the  form  of  decoction,  or  of  its  volatile  oil,  is  sometimes  used  as 
a  stimulant  emmenagogue  or  for  the  purpose  of  producing  abortion, 
but  is  a  very  unsafe  remedy.  When  taken  in  sufficient  amount  it 
causes  abdominal  pain,  vomiting,  loss  of  consciousness,  and  violent 
epileptiform  convulsions.!  The  minimum  fatal  dose  of  the  oil  of 
tansy  is  not  known,  but  in  two  cases3  a  teaspoonful  of  the  oil  pro- 
duced violent  epileptiform  convulsions,  and  the  same  aanount  is  said  to 
have  caused  death.  Recovery  is  stated  to  have  occurred  after  one  and 
a  half  fluidrachms  ;*  also  after  three  fluidrachms.5  The  action  of  the  oil 
upon  the  lower  animals  has  been  studied  by  Guillery.'  In  frogs  the 
most  important  effects  which  it  was  found  to  produce  were  paralysis  of 
the  peripheral  endings  of  the  motor  nerves,  with  early  appearance  of 
post-mortem  rigidity  ;  and  paralysis  of  the  vaso-motor  centre  of  the 
medulla  and  of  the  inhibitory  cardiac  apparatus,  with  at  last  paralysis 
of  the  heart  itself.  In  warm-blooded  animals  the  oil  produced  symp- 
toms precisely  similar  to  those  which  it  causes  in  man.  After  section  of 
the  spinal  cord  the  convulsions  did  not  occur  in  the  hind  legs  :  they  are 
therefore  of  cerebral  origin.  The  arterial  pressure  was  not  affected  until 
death  was  at  hand  :  so  that  it  is  evident  that  the  drug  has  little  action 
upon  the  heart. 

OLEUM  HEDEOM.E.  U.  S. — Under  the  name  of  oil  of  pennyroyal,  in 
the  United  States,  the  oil  of  the  Hedeoma  pulegioides  is  used  as  a  stimu- 
lating emmenagogue  in  domestic  practice,  but  has  very  little  power. 
Two  fluidrachms  taken  by  a  young  woman  produced  vertigo,  faintness, 
muscular  weakness,  frequent  feeble  pulse,  cold  skin,  and  cold  extremities 
(C.  A.  Bryce7).  Dose,  from  two  to  ten  minims  (o.  12-0.6  C.c. ).  In 
Europe  the  oil  of  Mentha  pulegium  is  known  as  oil  of  pennyroyal. 

APIOL. — Apiol  is  a  peculiar  non-nitrogenous,  yellowish,  oily  liquid, 
which  is  obtained  from  the  root  of  the  Apium  petroselinum,  or  common 
parsley.  According  to  its  discoverers,  Joret  and  Homolle,8  one  gramme 

*  Case  of  G.  F.  Cooper  ( Med.  Examiner,  N.  S.,  ix.  720). 

f  For  references  to  fatal  cases,  most  of  which  have  occurred  in  the  United  States, 
see  U.  S.  Dispensatory,  also  Guillery  (loc.  cit.).  Guillery  believes  that  the  symptoms 
caused  by  the  oil  and  by  tansy  tea  are  different.  In  a  case  of  poisoning  by  the  leaves, 
however,  reported  in  the  Nashville  Med.  and  Surg.  Journ.,  1879,  xxiii.,  the  symptoms 
were  those  alleged  to  be  characteristic  of  oil-poisoning ;  and  the  oil  probably  is  the  only 
active  principle  of  the  drug. 


744 


LOCAL   REMEDIES. 


of  it  will  produce  in  man  a  cerebral  excitation  very  similar  to  that  in- 
duced by  coffee,  without  other  symptoms.  In  doses  of  from  two  to  four 
grammes  it  causes  a  species  of  intoxication,  with  vertigo,  ringing  in  the 
ears,  and  severe  frontal  headache, — a  group  of  symptoms  very  similar  to 
those  seen  in  cinchonization. 

Apiol  has  been  used  to  a  considerable  extent  as  an  antiperiodic,  but 
it  is  certainly  of  very  inferior  rank.  It  was  originally  recommended  in 
anienorrhaca  by  Joret  and  Homolle,  who  exhibited  three  or  four  grains 
twice  a  day  for  a  week  preceding  the  time  in  which  the  return  of  men- 
struation was  due.  Whenever  any  symptoms  of  the  menstrual  molimen 
appear,  fifteen  grains  of  it  should  be  administered  in  the  course  of 
three  or  four  hours.  It  is  always  given  in  capsules,  each  of  which, 
as  imported  from  France,  usually  contains  one-quarter  of  a  gramme 
(3.9  grains). 

VIBURNUM  OPULUS.  U.  S. — Cramp-root.  VIBURNUM  PRUNIFO- 
LIUM.  U.  S.  Black  Haw. — These  remedies  are  believed  by  various 
practitioners  to  be  of  value  in  the  treatment  of  dysmenorrhcea  and  menor- 
rhagia,  and  ovarian  irritation.  FLUIDEXTRACTUM  VIBURNI  OPULI, 
U  S.,  or  FLUIDEXTRACTUM  VIBURNI  PRUNIFOLII,  U.  S. ,  maybe  given 
in  doses  of  one  to  four  fluidrachms  (4-16  C.c. )  three  to  four  times  a  day. 
The  solid  extract  is  sometimes  employed,  but  is  not  an  eligible  prepara- 
tion and  is  not  official. 


REFERENCES. 

EMMENAGOGUES.  4'  L.  M.  R.,  1882,  48. 

5-  Med.  Bull.,  1888,  x. 

1.  T.  G.,  1887,  iii.  6.  GUILLERY     .    .    .   .  B.  A.  R.  B.,  1878,  xii. 

2.  LETHHBY L.  L..  1845.  7.  BRYCE Southern  Clinic,  vi.  323. 

3.  Cincinnati       Lancet      and        8.  JORET  and   HOMOI.I.E  .  Journ.  de  Pharmacie, 

Clinic,  1881.  3  s.,  xxviii.  219. 


FAMILY   VIIL— OXYTOCICS. 


OXYTOCICS  are  those  remedies  which  are  employed  during  or  directly 
after  parturition,  to  increase  the  uterine  action.  Of  the  few  drugs  which 
have  claims  for  position  in  the  present  class,  quinine  has  already  been 
fully  considered  ;  it  apparently  differs  entirely  from  the  other  known 
oxytocics  in  not  producing  continuous  tetanic  spasms  of  the  uterus,  and 
is  therefore  the  safest  stimulant  to  parturition  at  our  command.  The 
peculiar  dangers  which  beset  the  use  in  labor  of  drugs  which  cause  uter- 
ine tetanus  will  be  fully  discussed  in  the  article  upon  ergot. 

ERGOTA— ERGOT.    U.S. 

Ergot  is  a  blackish  body,  one  to  two  inches  in  length,  irregularly 
cylindrical,  grooved  along  one  side,  and  very  generally  curved  ;  it  is 
composed  of  very  thick  walled  microscopic  cells,  containing  oil-drops 
but  no  starch.  As  was  first  demonstrated  by  Tulasne,1  ergot  is  the  sclero- 
tium  of  the  Claviceps  (C.  purpurea,  Tulasne)  which  infests  the  grain  of 
Secale  cereale,  or  rye. 

Among  the  lowest  of  vegetable  organisms,  and  distinguished  from  all  other 
plants  by  the  absence  of  chlorophyll,  are  the  fungi.  There  are  in  most  cases  two 
distinct  states  or  stages  in  the  life  of  a  fungus  :  in  the  first  of  these,  the  vegetating 
period,  it  exists  as  a  mycelium,  a  usually  filamentous  mass  or  flocculus,  whose  sole 
function  is  to  grow  and  increase  ;  in  the  second  stage  the  thai/us,  or  ordinary  fungus 
or  mushroom,  is  formed,  and  to  it  is  assigned  the  function  of  developing  repro- 
ductive bodies,  after  whose  maturation  it  perishes.  Between  these  stages  there  is  in 
some  fungi  an  intermediate  one,  in  which  the  plant  exists  as  a  sclerotium.  The 
genus  Claviceps  comprises  a  number  of  parasitic  fungi,  which  develop  in  the  pistils 
of  the  various  species  of  Graminea?.  The  first  appearance  of  the  ergot  is  in  the 
flower  of  the  rye,  at  the  base  of  whose  pistil  there  arises  a  minute  flocculent  mass 
of  mycelial  filaments.  These  filaments,  continually  growing  and  invading  all  parts 
of  the  tissue  of  the  pistil,  at  last  form  of  it  an  irregular  whitish  body,  at  the  base  of 
which  after  a  time  appears  a  dark-colored  body,  the  sclerotium,  which  continues  to 
grow,  lifting  up  the  diseased  and  withering  mass  formed  out  of  the  original  pistil, 
and  finally  developing  into  a  perfect  ergot.  If  a  fresh,  living  ergot  be  placed  in  a 
damp,  warm  place,  after  a  time  little  cracks  will  appear  in  its  surface,  and  through 
these  cracks  little  round  bodies  will  project,  and  finally  be  raised  up  on  stalks  and 
constitute  perfect  thalli, — minute  fungi,  which  finally  produce  spores. 

Ergot  is  an  exceedingly  complex  substance,  containing  nearly  thirty- 
five  per  cent,  of  an  inert  fixed  oil. 

745 


746  LOCAL   REMEDIES. 

A  large  number  of  substances  have  been  isolated  and  claimed  to  be  the  active 
principles  of  ergot.  It  is  probable  that  the  drug  owes  its  activity  to  a  number 
of  ingredients  rather  than  to  any  one  substance.  The  most  important  of  the  prin- 
ciples as  yet  discovered  is  the  resinous  body  sphacelotoxin,  isolated  by  Jacobi,"  which 
seems  to  be  identical  with  Robert's  sphacelinic  acid.  According  to  Jacobi  sphacelo- 
toxin enters  into  various  combinations  with  other  constituents  of  ergot,  two  of 
which  he  has  isolated  and  shown  to  be  physiologically  active  ;  namely,  chrysotoxin 
and  secalintoxin.  Robert 3  has  found  a  tetanizing  alkaloid  cornutine  which  is  also  a 
powerful  stimulant  to  the  uterus.  The  term  ergotin  has  been  applied  to  a  variety 
of  substances,  and  to-day  is  most  commonly  understood  to  refer  to  Bonjean's 
ergotin,  which  is  practically  a  watery  extract  of  the  drug. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Absorption  and  Elimina- 
tion.— The  preparations  of  ergot  have  a  very  feeble  local  action,  but  their 
irritant  properties  are  sufficient  to  interfere  with  their  hypodermic  use, 
and  sometimes  to  make  them  disturb  the  stomach.  They  yield  their 
active  principles  readily  to  absorption,  but  concerning  the  fate  of  these 
bodies  in  the  organism  we  have  no  knowledge. 

General  Effects. — Even  the  largest  therapeutic  doses  (an  ounce  of 
the  fluid  extract)  produce  in  man  no  perceptible  symptom  save  some 
nausea.  In  a  number  of  cases  death  has  resulted  from  abortion  caused 
by  large  doses  of  ergot,*  but  we  know  of  but  two  instances  of  serious 
poisoning  in  a  non-pregnant  person,  f 

In  the  first  case  gastric  irritation,  thirst,  diarrhoea,  burning  pain  in  the 
feet,  and  convulsions  are  said  to  have  preceded  death.  In  the  second 
case  (G.  S.  Oldright4),  two  hours  after  taking  the  drug  (amount  not 
stated)  there  were  developed  tingling  in  the  fingers  and  feet,  cramps  in 
the  legs,  arms,  and  chest,  with  dizziness  and  weakness  ;  the  pupils  were 
dilated,  the  pulse  was  very  small,  and  a  feeling  of  coldness  was  complained 
of.  These  symptoms  were  relieved  by  the  administration  of  stimulants 
and  the  use  of  external  heat  ;  after  a  time  they  recurred  with  greater 
violence  ;  finally,  under  the .  reinstitution  of  the  measures  previously 
employed,  the  face  became  intensely  congested  and  purplish  red,  pain  in 
the  head  was  felt,  the  patient  seemed  much  excited,  and  convulsions  were 
feared,  but  did  not  occur  ;  there  was  some  diarrhoea,  with  dark  gray 
stools. 

According  to  Diez  (quoted  by  Stille"),  the  principal  effects  of  poison- 
ous doses  of  ergot  are  in  the  lower  animals  profuse  salivation,  vomiting, 
dilatation  of  the  pupils,  hurried  breathing,  frequent  pulse,  cries,  trem- 
bling, staggering,  paraplegia,  in  some  cases  diarrhoea  and  urgent  thirst, 
convulsions,  and  death. 

Among  the  lower  animals  chickens  are  most  susceptible  to  the  action  of  ergot. 

*  For  cases,  see  Neubert  (Journ.  fiir  Pharmacodynamik,  1860,  ii.  483);  also,  same 
case  Richter  (Caspar's  Vierteljahrschrifl,  xx.  177);  Tardieu  (Ann.  d'Hyg.,  1855,  i. ; 
Toledo  Med.  and  Snrg.  Journ.,  July,  1878). 

t  Davidson  reports  a  case  with  fluid  blood,  jaundice,  and  universal  hemorrhages, 
attributed  with  doubtful  correctness  to  poisoning  by  ergot  (London  Lancet,  1882,  ii.  526). 


OXYTOCICS.  747 

In  these  it  produces  besides,  ataxia  and  general  weakness,  a  cyanosis  of  the  comb 
and  wattle  which  become,  if  the  dose  has  been  sufficient,  finally  gangrenous  and 
fall  off.  So  marked  is  this  effect  that  it  has  been  used  as  a  method  of  determining 
the  comparative  activity  of  different  specimens  of  the  drug.  It  is  asserted  that  in 
pigs  the  tips  of  the  ears  become  gangrenous.  The  mortification  is  due  to  obstruc- 
tion of  the  arteries  by  a  transparent  hyaline  mass  following  a  local  vascular  spasm. 

An  examination  of  the  above  summary  of  the  toxic  effects  of  ergot 
on  the  lower  animals  shows  that  the  symptoms  are  mainly  paralytic,  and 
that  the  only  ones  which  are  in  any  sense  characteristic  are  the  anaes- 
thesia and  the  coldness  of  the  surface.  As  this  coldness  of  the  surface 
has  been  noted  in  various  women  in  whom  the  drug  has  caused  fatal 
abortion,  it  is  probably  characteristic  of  the  poisoning. 

Nervous  System. — The  action  of  ergot  upon  the  general  nervous  sys- 
tem is  extremely  feeble,  but  is  not  well  understood  :  as  both  Wright  and 
Kohler  have  found  that  the  voluntary  muscles  are  not  affected  by  the  drug, 
the  motor  symptoms  of  the  poisoning  would  appear  to  be  of  nervous 
origin.*  The  statement  of  Eugene  Haudelin,7  that  the  peripheral  nerves 
are  not  affected,  has  been  confirmed  by  the  experiments  of  Kohler,  so 
far  as  concerns  the  motor  nerves  and  the  watery  extract  of  the  drug. 

According  to  Robert  cornutine  acts  as  a  convulsant  but  sphacelotoxin  is  a 
motor  depressant.  A  specimen  containing  excessive  amounts  of  cornutine  may 
therefore  cause  spasms  but  ordinarily  from  preparations  of  ergot  itself,  as  shown 
by  S.  A.|Wright5  the  paralysis  is  much  more  marked  than  the  spasms;  in  some 
cases  the  special  senses  seemed  to  be  destroyed,  and  coldness  of  the  surface  was  a 
very  prominent  symptom.  He  found  that  the  intravenous  injection  of  a  strong  infu- 
sion caused  immediate  dilatation  of  the  pupils,  great  increase  in  the  rate  of  the  car- 
diac pulsations,  paralysis,  and  convulsions  and  death  in  a  few  minutes  :  when  the  dose 
was  not  sufficient  to  kill  at  once,  great  anaesthesia  and  coldness  of  the  skin  and  also 
paralysis  of  the  special  senses  were  developed.  InKersch's6  experiments  intrave- 
nous injections  of  the  poison  caused  marked  coldness  of  the  surface  and  also  great 
muscular  rigidity.  Upon  rabbits,  according  to  Wright,  ergot  acts  very  feebly. 
Enormous  doses  of  ergot  are  required  to  produce  toxic  symptoms  in  animals,  since 
in  one  of  Wright's  experiments  an  amount  equivalent  to  two  drachms  for  every 
pound  weight  of  the  dog  failed  to  kill. 

Circulation. — According  to  the  observations  of  Parola,  Gibbon, 
Arnal,  Hardy,  Beatty  (quoted  by  Still6),  and  Bailly  and  S£e,8  very  large 
doses  of  ergot  reduce  the  pulse-rate  in  man,  but  only  under  the  rarest 
circumstances  below  sixty.  Eberty  found  that  in  the  frog  the  drug  still 
lessened  the  rate  of  the  cardiac  beats  after  destruction  of  the  medulla,  but 
that  in  the  atropinized  mammal  ergot  was  powerless  to  alter  the  cardiac 
rhythm.  By  toxic  doses  the  rapidity  of  the  heart's  action  is  increased, 
and,  according  to  Boreischa,  galvanization  of  the  parvagum  has  at  this 
time  little  or  no  effect  upon  the  pulse.  It  may  be  that  ergot  first  stimu- 


*  In  1884  T.  Korkorin,  in  a  St.  Petersburg  thesis,  affirmed  that  pronounced  and  char- 
acteristic pathological  alterations  can  be  found  in  the  spinal  cord  of  animals  slowly  killed 
with  ergot.  The  correctness  of  this,  however,  seems  to  be  more  than  doubtful.  See 
paper  by  A.  Grunfeld  (Archiv  f.  Psych,  u.  Nerven.,  1889-90,  xxi). 


748  LOCAL    REMEDIES. 

lates  and  then  paralyzes  the  peripheral  pneumogastric,  but  before  any 
conclusion  can  be  considered  established  further  investigation  is  imperative. 

In  1870  Charles  L.  Holmes9  found  that  ergot  injected  into  the  jugular 
vein  of  a  dog  caused  a  sudden  immediate  fall  of  the  blood-pressure,  fol- 
lowed in  a  short  time  by  a  marked  rise  above  the  normal.  This  fact  has 
been  confirmed  by  Kohler  and  Eberty,10  by  H.  C.  Wood,11  by  Robert 
and  by  Jacobi.  Plumier,39  however,  asserts  that  the  rise  is  insignificant, 
and  in  the  experiments  of  Sollman  and  Brown40  if  was  either  absent  en- 
tirely or  else  very  slight.  The  most  probable  explanation  of  the  results 
obtained  in  the  last  two  investigations  is  found  in  the  ease  with  which 
ergot  undergoes  spontaneous  decomposition.  Houghton  examined  some 
two  hundred  specimens  of  ergot,  many  ot  wnich  he  found  to  be  quite 
inert. 

The  primary  fall  of  pressure  is  probably  due  to  the  depressant  action 
of  an  excessive  amount  of  the  drug,  which  reaches  the  heart  in  concen- 
trated form  when  thrown  into  the  vein,  directly  upon  the  cardiac  muscle. 
Plumier  has  shown  that  ergot  thrown  into  the  isolated  mammalian  heart 
produces  at  first  almost  complete  extinction  of  cardiac  action,  followed 
by  a  prompt  return  to,  or  even  slightly  beyond,  the  normal. 

The  rise  in  pressure,  which  is  to  be  regarded  as  the  characteristic 
effect  of  ergot  upon  the  circulation,  is  due  to  a  constriction  of  the  blood- 
vessels. Holmes,  Wernich,1"'  Vogt,15  Kersch,  Schuller37  and  Boldt38  assert 
that  they  have  seen  invariably  diminution  in  the  caliber  of  the  arteries 
under  the  influence  of  ergot.*  According  to  Wood,  Hemmeter  and 
Kobert  the  rise  in  pressure  does  not  occur  after  section  of  the  spinal 
cord. 

It  appears  therefore  to  be  an  established  fact  that  ergot  causes  con- 
traction of  the  blood-vessels  and  consequent  rise  of  the  arterial  pressure 
by  stimulating  the  vaso-motor  centre  in  the  medulla.  There  is  however 
some  evidence  that  it  also  exerts  some  direct  stimulant  influence  on  the 
vessel-walls. 

The  evidence  which  has  been  brought  forward  in  favor  of  the  direct  stimulant 
action  of  ergot  upon  the  blood-vessel  fibres  consists  of  the  statements  of  Holmes, 
Wernich,12  and  J.  H.  Peton,"  that  after  the  nerves  going  to  certain  blood-vessels 
have  been  cut,  these  vessels  can  be  seen  to  contract  when  ergot  is  injected  into  the 
animal.  The  observations  of  Holmes,  Wernich,  and  Peton  are,  however,  in  dis- 
tinct contradiction  to  the  very  elaborate  experiments  of  Paul  Vogt,15  in  which  the 
dilated  vessels  in  the  ear  of  the  rabbit  whose  cervical  ganglion  had  been  extirpated 
could  not  be  made  to  contract  by  ergot.  Moreover,  any  observations  made  with 
the  eye  as  to  the  contractions  or  dilatations  of  the  blood-vessels  are  of  doubtful 
value. 

Greater  importance  should  be  attached  to  the  experiments  of  Ringer  and  Sains- 
bury,  made  upon  tortoises  according  to  the  method  of  Gaskell  (see  DIGITALIS, 
page  300).  In  these  the  addition  of  ergotin  greatly  slowed  the  rate  of  flow  through 

*  Patrick  Nicol  and  J.  Mossop  (Brit,  and  For.  Medico-Odr.  Kei1.,  1872, 1.)  have  noted 
with  the  ophthalmoscope  the  contraction  of  the  retinal  vessels  after  the  exhibition  of 
ergot  in  man. 


OXYTOCICS.  749 

the  arterioles,  but  in  these  experiments  it  was  found  that  the  addition  of  ergotin  to 
the  saline  solution  used  had  no  distinct  effect  until  there  was  ten  per  cent,  of  the 
extract  in  solution.  Ten  per  cent,  of  ergotin  is  enough  very  seriously  to  influence 
the  viscidity  of  the  saline  solution,  and  it  is  probable  that  the  slowing  effect  of  the 
ergotin  was  the  result  of  altered  physical  conditions. 

They  have  however  received  some  confirmation  in  the  investigations  of  Plumier 
who  found  that  perfusion  through  the  pulmonary  vessels  separated  from  the  central 
nervous  system  produced  a  slight  constriction  of  these  vessels,  and  of  Jacobi,  who 
found  that  the  rate  of  flow  through  the  vessels  of  the  leg  was  diminished  when  per- 
fused with  chrysotoxin. 

As  has  been  shown  by  Haudelin,  Boreischa,16  Brown- Sequard,17  and 
others,  the  toxic  dose  of  ergot  produces  immediately  or  after  a  time  a 
fall  of  the  arterial  pressure.  The  assertion  of  Brown-Se'quard,  that  this 
fall  of  arterial  pressure  is  due,  at  least  in  part,  to  a  vaso-motor  paralysis, 
is  corroborated  by  the  experiments  of  Boreischa,  who  found  that  when 
the  vessels  were  paralyzed  by  section  of  the  spinal  cord  high  up,  the  fall 
of  pressure  produced  by  the  toxic  dose  of  ergot  was  proportionately  not 
nearly  so  great  as  in  a  normal  animal.  The  fall  of  pressure  however  is 
brought  about  also  through  cardiac  failure  for  Hemmeter"  has  demon- 
strated that  the  isolated  heart  is  slowed  and  weakened  by  large  doses  of 
ergot  and  Eberty 42  found  that  the  heart  is  arrested  in  diastole  and  non- 
irritable. 

Bodily  Temperature. — The  coldness  of  the  surface  in  ergotic  poison- 
ing seems  to  depend  upon  a  general  fall  of  temperature.  Hemmeter 
has  noticed  that  this  fall  of  temperature  commonly  amounts  to,  and  often 
exceeds,  5°  C.  in  the  lower  animals  and  2°  F.  in  the  human  being.  The 
cause  of  it  has  not  been  made  out.  Hemmeter  states  that  in  several  ex- 
periments he  has  found  pronounced  reduction  of  urea  elimination  in  dogs 
under  the  influence  of  ergot,  and  believes  it  possible,  though  not  proved, 
that  the  fall  of  temperature  is  due  to  diminished  general  metabolism  ; 
it  may,  however,  be  only  a  secondary  phenomenon  due  to  the  action  of 
the  drug  upon  the  circulation. 

Action  on  the  Intestines. — The  muscle-fibres  in  the  coats  of  the  blood- 
vessels are  certainly  not  the  only  non-striated  muscles  influenced  by 
ergot.  According  to  Wertheimer  and  Magnin,18  ergot  produces  active 
movements  in  the  coats  of  the  stomach,  and  Wright  found  very  active 
intestinal  peristalsis  at  the  post-mortem  examinations  of  poisoned  ani- 
mals ;  further,  both  Wernich  and  Haudelin  bear  witness  to  the  violent 
intestinal  peristalsis  produced  in  the  lower  animals  by  toxic  doses  of 
ergot. 

Uterus. — Upon  the  uterus  of  parturient  women  or  of  the  parturient 
lower  mammal  ergot  exerts  a  very  pronounced  and  fixed  influence,  in- 
creasing the  length  and  force  of  the  pains,  and,  if  it  be  given  in  sufficient 
dose,  causing  after  a  time  violent  tetanic  cramp  of  the  whole  organ. 

The  action  of  ergot  in  producing  contraction  in  the  impregnated 
but  not  parturient  womb  is  by  no  means  so  constant.  Clinical  experience 
shows  that  in  pregnant  women  it  often  fails  to  originate  uterine  contrac- 


750  LOCAL   REMEDIES. 

tions.  Upon  animals  Wright  found  it  to  fail  in  all  of  a  number  of  trials, 
as  did  also  Bonjean  in  a  single  experiment.  On  the  other  hand,  Diez,* 
Oslere,*  and  Percy  and  Laurent*  found  it  to  cause  abortion  in  guinea- 
pigs,  sows,  rabbits,  cows,  and  cats  ;  and  Bodin  19  has  reported  an  epi- 
demic of  abortion  occurring  among  cows  near  Trois  Croix,  which  he 
attributed  to  feeding  upon  ergotized  grasses. 

Our  present  knowledge  indicates  very  strongly  that  the  uterine  con- 
tractions produced  by  ergot  are  of  centric  origin.  It  is  true  that  some 
years  ago  Boreischa  asserted  that  he  had  succeeded  in  producing  violent 
uterine  movements  with  ergot  after  division  of  the  nerve  connections  of 
the  organ,  but  the  result  reached  by  Wernich — namely,  that  no  ver- 
micular movements  are  produced  in  the  unimpregnated  womb  after  pre- 
vious section  of  the  spinal  cord — has  received  confirmation  from  John  C. 
Hemmeter.  In  repeated  experiments,  having  found  that  the  injection 
of  ergotin  produced  contractions  in  the  exposed  uterus  of  a  narcotized 
rabbit,  he  destroyed  the  spinal  cord  with  a  hot  wire,  and  determined 
that  ergot  was  no  longer  able  to  cause  uterine  contractions  :  that  the 
failure  of  the  ergot  in  these  cases  was  not  due  to  paralysis  of  the  uterus 
by  shock  was  then  demonstrated  by  injecting  ammonia  into  the  veins, 
when  violent  uterine  contractions  occurred. 

SUMMARY.— Ergot  can  scarcely  be  considered  to  be  a  poison,  but 
when  taken  in  enormous  amounts  it  is  capable  of  causing  vomiting, 
rapid  breathing,  -weakness,  growing  paralysis,  urgent  thirst,  peripheral 
and  cerebral  pains,  dilated  pupils,  great  feebleness  of  the  circulation, 
convulsions,  and  death,  the  most  characteristic  symptom  being  the 
great  fall  of  bodily  temperature.  The  method  by  which  these  symp- 
toms are  produced  has  not  yet  been  determined.  Therapeutic  doses  of 
ergot  increase  blood-pressure  by  stimulating  the  vaso-motor  centre  in 
the  medulla,  but  have  no  distinct  influence  upon  the  heart  or  the  walls 
of  the  arterioles.  Toxic  doses  depress  the  pressure  by  cardiac  paral- 
ysis, and  probably  also  by  paralysis  of  the  blood-vessels.  Ergot,  in  full 
therapeutic  doses,  so  acts  upon  the  centres  in  the  lower  spinal  cord 
which  preside  over  the  uterine  muscles  as  to  produce  in  the  parturient 
womb  violent  uterine  contractions,  a.nd  finally  uterine  tetanus. 

THERAPEUTICS. — Owing  to  the  power  that  ergot  possesses  of  intensi- 
fying labor-pains,  it  has  long  been  used  in  uterine  inertia  during  partu- 
rition. Indeed,  it  was  for  this  purpose  that  the  drug  was  first  employed 
in  medicine,  and  thereby  acquired  the  name  of  pulvis  parturiens.  The 
literature  of  the  subject  is  immense,  and  all  imaginable  opinions  as  to  the 
effects  of  the  drug  when  given  in  labor,  and  as  to  the  advisability  of  its 
employment,  have  been  advanced  ;  but,  without  discussing  these,  we 
shall  here  simply  point  out  the  clearly  established  rules  for  its  use  and 
the  clinically  determined  dangers  and  advantages  of  its  employment.  If 

*  Quoted  by  Still6  (  Therapeutics,  ad  ed.,  ii.  585). 


OXYTOCICS.  75i 

ergot  be  given  in  very  small  doses  during  labor,  the  natural  pains  are 
simply  intensified  ;  but  if  the  dose  be  large  enough  to  have  a  decided 
effect,  their  character  is  altered  :  they  become  not  only  more  severe  but 
much  more  prolonged  than  normal,  and  finally  the  intervals  of  relaxation 
appear  to  be  completely  abolished  and  the  intermittent  expulsive  efforts 
are  changed  into  one  violent,  continuous  strain.  It  is  evident  that,  if  the 
resistance  be  sufficiently  great,  this  may  endanger  the  safety  both  of  the 
mother  and  of  the  child.  The  dangers  to  the  mother  are  twofold  :  there 
is  a  possibility  of  the  uterus  rupturing  itself  by  its  efforts  ;  and,  when  the 
head  comes  down  upon  the  perineum,  if  the  soft  parts  be  rigid  there  is 
a  very  strong  probability  that  they  will  be  lacerated.  The  danger  of 
uterine  rupture  is,  we  think,  a  remote  one  ;  for  although  several  alleged 
cases  have  been  recorded,  yet  in  very  few  is  the  accident  clearly  trace- 
able to  the  asserted  cause.*  The  fatal  character  of  the  accident  is  such, 
however,  that  the  possibility  of  its  occurrence  should  always  prevent  the 
reckless  use  of  the  drug. 

The  improper  use  of  ergot  is  far  more  serious  in  its  effects  upon  the 
child  than  upon  the  mother.  During  a  violent  uterine  contraction  the 
passage  of  the  blood  from  the  placenta  to  the  child  must  be  interfered  with, 
or,  in  other  words,  the  respiration  of  the  foetus  is  temporarily  stopped, 
so  that  its  life  depends  upon  the  aeration  of  the  blood  during  the  intervals. 
If  the  latter  be  very  much  shortened,  the  life  of  the  child  is  greatly  im- 
perilled ;  and  if  they  be  abolished,  it  must  be  destroyed,  unless  delivery 
occurs  in  a  very  few  moments.  These  considerations  are,  we  think,  suf- 
ficient, without  further  discussion,  to  show  the  imperativeness  of  the  rule 
never  to  give  ergot  in  uterine  inertia  when  there  is  much  resistance,  either 
in  the  bony  or  in  the  soft  parts  of  the  mother.  In  primiparae  such  resist- 
ance is  always  to  be  looked  for,  and  its  degree  often  difficult  to  judge  of 
beforehand  ;  and  in  such  women  ergot  should  not  be  used  for  the  pur- 
poses of  expulsion.  Even  under  the  most  favorable  circumstances — 
when  the  woman  has  previously  borne  children,  when  the  bony  pelvis  is 
capacious,  and  the  soft  parts  are  relaxed  and  dilatable — its  use  should 
be  entered  upon  with  caution  ;  and  if  the  accoucheur  be  skilful  in  the 
application  of  instruments,  cases  must  be  rare  in  which  the  latter  are  not 
preferable  to  the  ecbolic. 

In  women  of  lax  fibre,  with  roomy  pelves,  ergot  may  be  used  in 
uterine  inertia  if  instruments  are  not  at  hand,  or  if  they  are  objected  to, 
or  if  the  obstetrician  is  timid  in  their  application. 

At  the  close  of  parturition,  ergot  is  very  commonly  employed  to 
prevent  post-partum  hemorrhage ;  and  in  this  case  there  is  no  objection 
to  its  use,  and  the  remedy  is  invaluable.  But,  as  it  requires  from  fifteen 
to  twenty  minutes  for  its  action  when  given  by  the  mouth,  ergot  exhib- 
ited in  this  way  cannot  be  relied  upon  to  arrest  flooding  when  it  has 
already  set  in.  To  prevent  the  occurrence  of  the  latter,  it  is  an  excel- 

*  See  Stilte  (  Therapeutics,  2d  ed.,  ii.  591). 


752  LOCAL    REMEDIES. 

lent  rule  to  give  a  full  dose  of  the  ecbolic  when  the  child's  head  is  well 
down  upon  the  perineum  and  beginning  to  emerge  at  the  vulva.  After 
labor,  if  a  tendency  to  bleeding  is  manifested,  ergot  may  be  administered 
hypodermically. 

For  the  induction  of  premature  labor,  ergot  has  been  and  still  is  to 
some  extent  used  ;  but  it  is  uncertain  in  its  action,  and  offers  no  advan- 
tages over  instrumental  methods. 

The  success  of  ergot  in  arresting  hemorrhage  after  labor  soon  led  to  its 
use  in  uterine  hemorrhages  in  other  than  parturient  or  pregnant  women  ; 
and  the  next  step  beyond  this  was  its  employment  in  other  hemorrhages. 
In  all  forms  of  hemorrhage  in  which  no  direct  local  application  can  be 
made,  ergot  is  to-day  probably  the  most  generally  used  remedy.  It  is 
thus  employed  in  menorrhagia,  haemoptysis,  hemorrhage  from  the  giims, 
epistaxis,  etc.  Even  mpurpura  h&morrhagica,  the  hypodermic  injection 
has  been  highly  praised.*  The  value  of  ergot  as  a  styptic  in  an  internal 
hemorrhage  is  generally  attributed  to  its  power  of  contracting  blood-ves- 
sels. It  must  be  remembered  however  that  any  substance  which  leads  to 
a  general  vaso-constriction  increases  the  force  of  the  circulation.  The  in- 
creased pressure  tends  to  dislodge  any  clot  which  may  be  formed  at  the 
bleeding  point.  Therefore  those  drugs  which  narrow  the  lumen  of  the 
vessels  must  incline  to  continue  rather  than  check  internal  hemorrhages. 

In  colliquative  night-sweats  due  to  relaxation  of  the  blood-vessels, 
ergot  is  a  most  efficient  remedy. 

Allied  to  its  use  in  hemorrhage  is  the  employment  of  ergot  in  enlarge- 
ment of  the  spleen  from  various  causes.  Da  Costa  *°  was  the  first  to  sug- 
gest hypodermic  injections  of  the  drug  for  this  purpose,  and  he  asserts 
that  he  has  even  cured  leukezmia. 

Led  by  the  probably  erroneous  belief  that  ergot  acts  upon  the  muscle- 
fibres  in  the  walls  of  the  blood-vessels,  Langenbeck  21  injected  the  drug 
into  the  immediate  vicinity  of  the  diseased  blood-vessels  for  the  cure  of 
aneurism,  with  asserted  extraordinary  success.  The  practice  has  been 
followed  by  various  surgeons,  not  only  in  diseases  of  the  arteries  but  also 
for  the  relief  of  varicose  veins.  A  great  deal  of  local  swelling  and  hard- 
ness is  induced,  involving  the  blood-vessels  themselves,  and  the  good 
which  has  been  achieved  is  probably  simply  the  result  of  the  local  inflam- 
mation, the  ergot  acting  as  an  irritant  and  having  no  specific  action. 

Very  many  years  ago  F.  E.  Barlan-Fontayral 22  proposed  the  use 
of  ergot  in  chronic  dysentery  and  diarrhoea,  on  account  of  its  power  of 
causing  contraction  of  the  capillaries  ;  and  Massolaz,  in  an  epidemic  of 
chronic  diarrhoea  among  the  French  troops  serving  in  the  East,  found 
that  the  suggestion  was  well  timed.  Although  Barlan-Fontayral  after- 
wards published  a  book  f  upon  the  subject,  it  attracted  little  or  no  atten- 


*  Cases,  Brit.  Med.  Journ. ,  1874,  ii.;  Phila.  Med.  Times,  v. 

\Le  Seigle  ergote  et  V  Application  de  V Ergotine  d  la  Cure  de  la  Dyssenterie  et  de 
la  Diarrhee  chroniqttes,  Montpellier,  1858. 


OXYTOCICS.  753 

tion.  In  1871  A.  Luton,28  of  Rheims,  stated,  as  something  new,  that 
he  had  used  ergot  with  remarkable  success  in  a  violent  and  protracted 
epidemic  of  dysentery.  Successful  cases  of  chronic  diarrhcea  are  also 
reported  by  other  observers,2*  so  that  trials  of  the  remedy  should  be 
made  in  all  obstinate  cases. 

Another  employment  of  ergot  for  the  purpose  of  restraining  exces- 
sive secretion  is  in  galactorrh&a,  in  which  affection  it  has  been  used  with 
success  by  Le  Gendre,25  who  was  led  to  employ  it  by  an  observation  of 
Poyet  and  Commarmond,26  that  wet-nurses  fed  upon  ergotized  bread  lost 
their  milk. 

The  action  of  ergot  upon  the  blood-vessels  suggests  its  employment 
in  those  cases  in  which  there  is  local  or  general  dilatation  of  the  vessels. 
We  have  used  it  in  pulmonic  congestion  with  apparent  good  results,  and 
it  has  been  highly  lauded  in  the  first  stages  of  pneumonia  by  N.  S. 
Davis,21  by  Sunol,28  and  later  by  other  clinicians.  It  has  been  especially 
noted  by  J.  E.  Kelly,29  as  giving  immediate  relief  when  injected  hypo- 
dermically  in  low  forms  of  pulmonary  hyper&mia,  such  as  occur  in 
typhoid  fevers.  Ergot  has  also  been  recommended  by  O.  Rosenbach, 
as  a  means  of  raising  blood-pressure  in  cases  of  cardiac  disease  where 
there  is  thought  to  be  insufficient  peripheral  resistance  ;  and  Hemme- 
ter  believes  that  the  dicrotic  pulse  is  due  to  a  very  low  degree  of  pressure 
in  the  arterial  system,  and  is  an  indication,  especially  in  chronic  cardiac 
disease,  for  the  use  of  ergot.  Rosenbach  recommends  the  drug  strongly 
in  aortic  insufficiency  with  cardiac  dilatation.  Ergot  would  seem  to  be 
indicated  as  a  vaso-motor  stimulant  in  surgical  shock,  but  is  much  less 
prompt  in  its  influence  than  atropine.  As  originally  suggested  by  Brown- 
Se'quard,  it  is  still  much  used  for  the  relief  of  chronic  cerebral  and  spinal 
congestion.  When  there  is  a  rupture  of  the  vessels,  as  in  apoplexy,  by 
increasing  the  blood-pressure  it  tends  to  do  harm  rather  than  good.  It 
is  largely  used  for  the  relief  of  congestive  headaches,  and  has  been  em- 
ployed in  epilepsy,  in  which  disease,  according  to  Hemmeter,  it  greatly 
increases  the  efficiency  of  the  bromides.  Dehenne M  states  that  he  has 
obtained  most  remarkable  effects  in  the  relief  of  diabetes  by  subcutaneous 
injections  of  ergotin.  The  general  clinical  experience,  however,  seems 
to  be  that  whilst  occasionally  ergot  does  great  good  in  diabetes,  it  usually 
fails  to  accomplish  anything.  When  successful,  it  rapidly  diminishes  the 
glycosuria,  thirst,  and  polyuria.  In  diabetes  insipidus,  though  it  often 
fails,  ergot  is  perhaps  the  most  generally  useful  remedy  that  we  have. 

In  1872  Hildebrandt 31  announced  that  in  nine  cases  of  fibroid  tumors 
of  the  uterus  he  had  used  with  the  utmost  advantage  hypodermic  injec- 
tions of  ergotin,  and  this  practice  has  been  followed  very  widely  on  this 
continent.  It  is  scarcely  to  be  doubted  that  cures  are  sometimes 
effected  ;  but  probably  in  the  majority  of  cases  *  the  drug  simply  lessens 

*  See  Amer.  Jonrn.  Med.  Sci.,  July,  1873  ;  Amer.  Practitioner,  May,  1873,  May,  1874, 
August,  1874;  Clinic,  April,  1873;  Lancet,  May,  1873;  Chicago  Med.  Journ.,  1874;  and 
especially  Byford's  Address  (  Trans.  Amer.  Med:  Assoc.,  1875). 

48 


754  LOCAL    REMEDIES. 

the  uterine  congestion,  and  does  good  precisely  as  it  does  in  chronic  or  sub- 
acute  metritis  and  in  subinvohition  and  hypertrophy  of  the  uterus  (Mead- 
ows*2) ;  it  may  be  that  sometimes  it  strangles  the  growth  by  causing 
uterine  contractions.  If  the  latter  be  the  case,  a  cure,  as  is  suggested 
by  Goodell,33  is  to  be  expected  from  the  remedy  only  in  mural  and  sub- 
mucoid  tumors. 

An  objection  to  the  method  of  Hildebrandt  is  the  great  pain  and  local 
inflammation  which  often  result  ;  and  Goodell  proposes  as  a  substitute  the 
use  of  enemata  or  suppositories  containing  the  drug. 

TOXICOLOGY. — Enough  has  already  been  said  in  regard  to  the  acute 
poisoning  by  ergot,  except  it  be  to  state  that,  when  abortion  is  threat- 
ened from  its  ingestion,  in  the  maintenance  of  perfect  quiet  and  in  the 
free  exhibition  of  opium  are  to  be  found  all  the  measures  of  relief  at  our 
command. 

Since  the  days  of  Galen  there  have  swept  over  larger  or  smaller  dis- 
tricts of  Europe  epidemics  of  diseases  which  have  been  attributed  to 
ergot.  In  many  parts  of  Europe  rye  bread  forms  the  great  staple  article 
of  food  of  the  lower  classes.  It  always  contains  a  small  quantity  of 
ergot,  but  not  enough  to  have  any  deleterious  effect  upon  the  health. 
When  the  summer  is  wet  and  cold,  the  rye  becomes  very  extensively 
ergotized,  so  that  the  fungus  constitutes  a  large  proportion  of  the  mate- 
rials entering  into  the  bread.  It  is  under  these  circumstances  that  there 
occur  epidemics  of  ergotism  or  chronic  ergotic  poisoning.  It  is  not 
always  the  rye  that  causes  these  frightful  losses  of  life,  as  Heusinger14 
has  traced  one  epidemic  to  diseased  oats.  Before  going  further,  it  seems 
proper  to  state  that  Trousseau  and  Pidoux  assert  that  these  epidemics 
are  not  dependent  upon  any  specific  action  of  ergot,  but  are  either  epi- 
demics of  blood  diseases  or  simply  the  results  of  improper  and  insufficient 
food, — the  outcomes  of  poverty,  wretchedness,  and  famine.  It  seems  to 
us  indisputable  that  some  of  the  various  epidemics  which  have  been  re- 
corded were  of  this  character,  but  certainly  it  is  no  less  indisputable  that 
others  were  not.  Moreover,  numerous  scattered  cases  are  on  record  in 
which  a  few  persons  or  a  family  have  been  affected  with  ergotism  unmis- 
takably traceable  to  the  use  of  bread  largely  composed  of  the  fungus.* 

The  scope  of  the  present  treatise  is  such  as  to  forbid  our  entering  into 
an  elaborate  discussion  of  the  epidemics  of  ergotism,  especially  as  the 
subject  has  no  practical  bearing  so  far  as  the  American  profession  is  con- 
cerned, since  the  absence  of  deep  poverty  is  so  complete  in  our  country 
that  no  one  would  feed  on  largely  ergotized  bread  ;  and,  in  fact,  no  case 
of  ergotism  has  as  yet  been  recorded  as  occurring  in  the  United  States,  f 

*  For  an  account  of  a  modern  epidemic,  see  Deutsch.  Arch.f.  Klin.  Med.,  xxxiii.  246. 
t  Any  one  especially  interested  in  the  subject  will  find  the  literature  very  well  repre- 
sented in  the  references  of  Stille's  work  on  Therapeutics,  Duboue's  Recherches  sur  les 
Proprttlts  Therapeutiques  du  Seigle  Ergote,  Paris,  1873,  and  Husemann's  Handbuch  der 
Toxicologie. 


OXYTOCICS.  755 

There  are  two  varieties  of  ergotism, — the  gangrenous  and  the  spas- 
modic. In  some  epidemics  the  cases  have  been  of  mixed  type. 

Gangrenous  ergotism  has  been  especially  observed  in  France,  and  is  believed 
to  be  the  same  as  the  Ignis  Safer  or  the  Ignis  Sancti  Antonii  of  the  Middle  Ages, 
— an  affection  which  in  922  killed  forty  thousand  persons  in  Southwestern  France, 
and  in  1128-29  fourteen  thousand  in  Paris  alone.  It  generally  commences  with 
itching  and  formications  in  the  feet,  severe  pain  in  the  back,  contractions  in  the 
muscles,  nausea,  giddiness,  apathy,  with  abortion  in  pregnant  women,  in  suckling 
women  drying  of  the  milk,  and  in  maidens  amenorrhcea.  After  some  time  deep, 
heavy,  aching  pains  in  the  limbs,  an  intense  feeling  of  coldness,  with  real  coldness 
of  the  surface,  profound  apathy,  and  a  sense  of  utter  weariness  develop  them- 
selves. Then  a  dark  red  spot  appears  on  the  nose  or  on  one  of  the  extremities  ; 
all  sensation  is  lost  in  the  affected  part ;  the  skin,  perhaps  over  a  large  surface, 
assumes  a  livid  red  hue,  and  in  the  foci  of  local  changes  bullae  filled  with  serum 
appear.  The  adynamic  symptoms,  in  severe  cases,  deepen  as  the  gangrene 
spreads,  until  finally  death  puts  an  end  to  the  scene.  Very  generally  the  appetite 
and  digestion  are  preserved  to  the  last,  and  not  rarely  there  is  an  almost  ferocious 
hunger.  The  gangrene  is  generally  dry,  the  parts  withering  and  mummifying  ;  but 
sometimes  it  is  moist,  and  pyaemic  symptoms  may  even  be  developed.  Of  course 
a  very  large  number  of  cases  do  not  terminate  in  death  ;  but  the  part  immediately 
affected  is  generally  lost.  In  these  cases  the  toes  most  generally  are  the  portion 
destroyed,  but  it  may  be  any  one  or  all  of  the  extremities  ;  and  the  nose,  lips,  ears, 
and  even  the  buttocks  sometimes  bear  the  brunt  of  the  disorder. 

Spasmodic  ergotism  may  in  the  lightest  cases  be  manifested  only  by  itching, 
formications,  numbness,  or  complete  anaesthesia  of  the  fingers  and  toes  or  of  the 
buttocks,  and  by  gastro-intestinal  irritation,  as  shown  by  colic,  vomiting,  diarrhoea, 
or  constipation,  and  withal  a  ravenous  hunger.  In  more  severe  cases  these  mani- 
festations are  intensified,  and  spasmodic  symptoms  appear,  violent  and  painful 
tonic  contractions  affecting  especially  the  flexors  of  the  extremities,  interrupted  at 
times  by  intervals  of  quiet,  but  gradually  growing  into  severe  general  tetanic  parox- 
ysms, with  opisthotonos  and  emprosthotonos.  In  the  intervals  there  are  very  gen- 
erally muscular  tremblings,  and  as  the  case  progresses  there  are  developed  cerebral 
manifestations,  such  as  disturbances  of  vision,  photophobia,  chromopsia,  hemiopia, 
and  periodic  amblyopia  and  amaurosis,  giddiness,  cataleptic  and  epileptic  parox- 
ysms with  or  without  loss  of  consciousness,  delirium,  and  idiocy.  Gastro-intestinal 
symptoms  are  always  very  marked,  but  with  them  are  a  characteristic  ravenous 
hunger  and  a  longing  for  sour  food  and  drink.  The  skin  is  earthy  or  yellowish 
in  tint,  and  is  often  spotted  with  boils  or  pustules  or  semi-grangenous  vesicles. 
Death  is  apparently  caused  by  exhaustion  ;  and  in  those  that  recover,  various  local 
paralyses,  habitual  spasms,  amaurosis,  mental  aberrations,  or  even  idiocy  often 
remain  through  life.  In  a  few  cases  the  symptoms  are  still  more  violent,  and  the 
spinal  and  cerebral  disturbances  soon  lead  to  death. 

The  primary  changes  in  ergotism  are  in  the  blood-vessels.  Ergotic 
gangrene  can  readily  be  produced  in  the  comb  and  tongue  of  chickens, 
and  Von  Recklinghausen  asserts  that  the  essential  lesion  in  these  cases 
is  hyaline  thrombi  in  the  arterioles  and  capillaries;  whilst  Griinfeid35  has 
found  the  walls  of  the  vessels  thickened,  structurally  changed,  and  their 
lumen  occupied  by  thrombi  which  in  some  places  are  full  of  blood-cor- 
puscles and  in  other  parts  undergoing  hyaline  degeneration. 

ADMINISTRATION. — Ergot  should  not  be  administered  in  substance. 


756  LOCAL   REMEDIES. 

The  wine  (ViNUM  ERGOTS — twenty  per  cent.,  U.  S. )  is  very  feeble; 
ecbolic  dose,  half  to  two  fluidounces  (15-60  C.c. ).  The  fluid  extract 
(FLUIDEXTRACTUM  ERGOTS,  U.  S. )  is  a  very  efficient  preparation; 
ecbolic  dose,  one  to  two  fluidrachms  (4-7  C.c.),  repeated  in  twenty  min- 
utes, if  necessary  ;  in  nervous  diseases  much  larger  doses  are  required: 
thus  in  congestion  of  the  spinal  cord  we  usually  begin  with  half  an  ounce, 
and  increase  it  to  an  ounce  three  times  a  day.*  Extract  of  ergot  (Ex- 
TRACTUM  ERGOTS,  U.  S. )  is  preferable  to  the  fluid  extract  when  time  is 
not  important,  as  being  less  apt  to  cause  nausea.  When  administered 
by  the  mouth,  it  should  be  given  in  capsules  containing  from  five  to  seven 
grains  (o.  3-0. 46  Gm. )  Its  strength  is  five  times  that  of  the  fluid  ex- 
tract ;  when  used  hypodermically,  five  grains  should  be  dissolved  in  five 
minims  of  glycerin,  fifteen  minims  of  boiled  water,  and  one-fourth  of  a 
minim  of  carbolic  acid,  and  filtered  :  the  danger  of  causing  severe  local 
trouble  is  lessened  by  plunging  the  nozzle  of  the  syringe  deeply  into 
the  muscular  tissues. 

JBonjean's  ergotin,  so-called,  is  a  refined  watery  extract,  practically  the  official 
extract.  Wiggers1  s  ergotin,  which  contains  everything  in  ergot  insoluble  in  water, 
should  not  be  employed  therapeutically.  (See  Kohler56. )  The  attempt  to  assay 
preparations  of  ergot  by  their  action  upon  the  comb  of  the  cock  is  of  doubtful  utility; 
it  is  at  present  uncertain  whether  the  action  of  ergot  upon  the  uterus  and  upon 
blood-vessels  is  due  to  one  or  to  several  more  or  less  antagonistic  substances. 

HYDRASTIS.     U.  S. 

The  rhizome  and  roots  of  Hydrastis  Canadensis,  an  indigenous  per- 
ennial, commonly  known  as  Golden  Seal.  Hydrastis  contains  the  alka- 
loid berberine,  to  which  it  owes  its  yellow  color,  and  probably  also  two 
other  alkaloids,  canadine^  and  xanthopuccine,  besides  its  characteristic 
alkaloid,  hydrastine.\  The  latter  occurs  in  brilliant  four-sided  prisms, 
inodorous  and  almost  tasteless,  but  having  a  very  bitter  and  somewhat 
acrid  taste  when  in  the  form  of  a  salt.  Pure  hydrastine  and  its  salts  can 
be  obtained  in  the  shops,  but  the  hydrastzw  of  commerce  is  an  impure 
body  containing  berberine,  hydrastm*?,  and  probably  other  more  or  less 
active  alkaloids  besides  resin. 

PHYSIOLOGICAL  ACTION. — There  appear  to  be  no  cases  on  record  of 

*  It  would  appear  that  sometimes,  owing  to  idiosyncrasies,  even  small  amounts  of 
ergot  cause  much  disturbance.  Thus,  R.  B.  Faulkner  reports  (New  York  Med.  Journ., 
June  14,  1884)  a  case  in  which  a  fluidrachm  of  the  fluid  extract  caused  great  sleepiness, 
swelling  and  redness  of  the  feet,  and  violent  prickling  of  the  extremities,  probably  as  the 
outcome  of  gastric  irritation. 

t  According  to  the  experiments  of  Bunge,1  canadine  in  toxic  doses  produces  a  brief 
stage  of  psychical  and  motor  excitability,  followed  by  general  paralysis  and  depression, 
with  death  from  respiratory  paralysis,  and  has  little  direct  action  upon  the  blood-pressure. 
The  rate  of  pulsation  in  the  isolated  frog's  heart  is  lessened,  but  the  work  done  is  not 
decreased  by  the  moderate  dose ;  larger  doses  paralyze  the  muscle  of  the  heart.  The 
voluntary  muscles  are  not  affected  by  the  alkaloid,  nor  is  the  uterus,  although  diarrhoea 
with  violent  intestinal  peristalsis  is  produced. 

J  For  an  article  on  the  chemical  and  physiological  activities  of  a  number  of  deriva- 
tives from  hydrastine  by  Falck,  see  Virchow's  Archiv,  1895,  cxlii. 


OXYTOCICS.  757 

serious  poisoning  from  any  of  the  alkaloids  of  hydrastis,  and  in  the 
only  case  of  poisoning  by  the  crude  drug,  nine  grammes  of  the  fluid  ex- 
tract produced  vomiting,  giddiness,  headache,  dyspnoea  ;  a  slow,  weak, 
irregular  pulse,  mydriasis,  and  hallucinations  of  sight  (Friedeberg  !).  As 
hydrastis  is  chiefly  used  in  the  form  of  its  alkaloids,  we  shall  consider 
these  principles  separately.  The  alkaloid  hydrastine  is  so  dominant  in 
its  action,  that  to  it  is  chiefly  due  the  influence  of  the  crude  drug. 

Berberine  is  an  inactive  alkaloid,  Buchner  having  taken  twenty  grains 
with  very  little  effect.  In  doses  of  from  two  to  five  grains  (o.  1-0.3  Gm. ) 
it  is  a  simple  bitter,  and  as  such  may  be  given  in  pill  or  alcohol. 

Toxic  doses  of  berberine  cause  in  the  lower  animals  diarrhoea,  rapid  loss  ot 
flesh,  tremors,  diminished  respirator)'  action,  progressive  paralysis,  lessening  of  the 
pulse-rate,  depression  of  the  arterial  pressure,  partial  anaesthesia,  albuminous  or 
bloody  urine,  and  in  some  cases  final  convulsions.  (Falck  and  Guenste  ;s  Mosse 
and  Tautz.4)  After  death  hemorrhagic  nephritis  may  be  found.  Both  Schurinow 
and  Curci5  agree  that  berberine  causes  the  arterial  pressure  to  fall  rapidly  from 
vaso-motor  paralysis  ;  the  peripheral  vagus  is  paralyzed.  (Schurinow,  Marfori,6 
denied  by  Curci. )  According  to  Curci,  the  heart-muscle  is  directly  affected. 
Schurinow  and  Mosse  aud  Tautz  are  in  accord  in  asserting  that  the  nerve-trunks  are 
especially  implicated  in  the  poisoning,  but  Curci  believes  that  the  motor  and  sen- 
sory disorders  are  due  to  an  action  upon  the  spinal  cord  ;  probably  both  the  cord 
and  the  nerve-trunks  are  affected. 

Hydrastine  causes,  in  animals,  increased,  followed  after  a  time  by 
lessened,  respiratory  movements,  salivation,  vomiting,  excessive  peri- 
stalsis, muscular  tremblings,  weakness  and  rigidity,  loss  of  voluntary 
movement,  rise  of  bodily  temperature  (Bunge)  (often  followed  by  a  fall), 
feeble,  rapid  pulse,  clonk:  and  tetanic  convulsions,  increased  reflex  activity, 
and  death  from  cramp-asphyxia  or  general  paralysis,  or  exhaustion  with 
respiratory  failure.  Hydrastine  is  probably  eliminated  through  the  kid- 
neys. (See  Phillips  and  Pembrey.7) 

In  a  research  upon  the  effect  on  the  lower  animals  of  the  long-continued  use 
of  hydrastine  and  hydrastinine,  J.  De  Vos8  found  that  these  alkaloids  have  no 
cumulative  action,  but  that  gradually  the  animals  seem  to  become  accustomed  to 
their  use.  Neither  of  them  in  any  way  disturbed  the  gastric  or  intestinal  digestion. 
Albuminuria  never  occurred,  nor  was  there  apparent  disturbance  of  assimilation. 

Nervous  System. — So  far  as  is  known,  hydrastine  has  little  or  no 
action  upon  the  cerebral  hemispheres,  but  is  a  very  powerful  stimulant 
to  the  motor  side  of  the  spinal  cord.  Death  may  occur  during  the  period 
of  violent  convulsions  with  heightened  reflex  activity  ;  but  if  the  animal 
survives,  there  follows  a  general  paralysis,  which,  as  the  alkaloid  is  a 
marked  depressant  to  the  motor  nerve-trunks,  is  probably  of  peripheral 
origin. 

According  to  Cerna,9  when  voluntary  movements  and  the  reflexes  are  first 


758  LOCAL    REMEDIES. 

depressed  in  the  frog,  the  reflexes  can  be  restored  by  section  of  the  cord,  so  that  the 
palsy  is  probably  due  to  stimulation  of  Setschenow's  centre;  later  it  is  irremediable. 
Late  in  a  protracted  poisoning,  and  after  death,  the  motor  nerves  are  depressed  or 
altogether  paralyzed  (Falck,  Cerna),  and  Bunge '  has  found  that  the  local  appli- 
cation of  a  solution  of  the  alkaloid  to  a  nerve  kills  it.  According  to  Falck,  hydras- 
tine  placed  in  the  eye  has  no  effect  upon  the  sensitiveness  of  the  conjunctiva,  but 
both  Slavatinski  (quoted  by  Bunge)  and  Mays  affirm  that  late  in  the  poisoning 
there  is  general  loss  of  sensibility.  Mays  further  states  that  when  brought  in  con- 
tact with  a  nerve-trunk,  hydrastine  paralyzes  its  sensory  fibres,  although  tying  an 
artery  does  not  prevent  the  development  of  anaesthesia  in  general  poisoning  by  the 
alkaloid.  If  these  experiments  be  correct,  the  alkaloid  acts  both  upon  the  sensory 
cord  and  sensory  nerve  ;  this  action,  however,  is  entirely  subordinate  to  its  influence 
upon  the  motor  tract. 

Muscles. — Upon  the  muscles  the  alkaloid  has  some  influence,  since 
both  Falck  and  Bunge  have  found  that  its  not  too  dilute  solution  directly 
applied  to  a  muscle  destroys  its  contractile  power,  a  conclusion  which  is 
confirmed  by  Cerna,  who  further  states  that  preceding  the  depression 
there  is  a  stage  of  excitation  in  which  the  muscular  contraction  under 
stimuli  is  more  complete  and  prolonged  than  normal. 

Respiration. — When  death  takes  place  during  a  convulsion,  it  prob- 
ably is  due  to  cramp-asphyxia  ;  but  when  it  occurs  during  the  paralytic 
stage,  it  is  from  paralytic-asphyxia  (probably,  in  part  at  least,  of  centric 
origin),  the  heart-beat  continuing  after  death  (Serdzeff  "). 

Circulation. — The  characteristic  primary  effect  of  a  full  dose  of  hydras- 
tine  upon  the  circulation  is  a  rise  of  the  arterial  pressure  with  slowing  of 
the  pulse-rate,  this  condition  being  followed  after  a  time,  if  the  dose  has 
been  toxic,  by  a  fall  of  the  arterial  pressure.  The  rise  of  the  arterial 
pressure  is  probably  due  in  part  to  a  direct  action  upon  the  heart  itself 
and  in  part  the  result  of  contraction  of  the  blood-vessels,  caused  probably 
by  an  action  upon  their  muscle-fibres.  Marfori  believes  that  the  vaso- 
motor  centres  are  also  stimulated,  but  at  present  this  is  only  a  probability. 
The  fall  of  the  arterial  pressure  is  in  part  of  cardiac  origin,  there  being  in 
the  later  stages  of  the  poisoning  a  depression  of  the  heart  muscle,  which 
ends  in  diastolic  arrest  with  loss  of  muscular  irritability. 

When  hydrastine  in  sufficient  dose  is  injected  directly  into  the  circulation 
there  is  an  immediate  fall  of  pressure,  followed  by  a  marked  and  long-continuing 
rise  unless  the  original  dose  has  been  excessively  large,  when  the  pressure  falls 
progressively  until  death.  (See  the  observations  of  Bartholow,12  of  Fellner,10  of 
Falck,  of  Serdzeff  (quoted  by  Bunge),  of  Marfori,  and  of  Pellacani.)  The  primary 
fall  of  pressure  does  not  occur  after  subcutaneous  injections  (Falck),  and  is  due  to 
direct  action  of  the  concentrated  drug  upon  the  heart.  That  the  rise  of  pressure  is 
partly  of  cardiac  origin  is  proven  by  the  following  facts  :  Marfori,  also  Phillips  and 
Pembrey,43  have  noted  that  when  hydrastine  is  applied  to  the  isolated  frog's  heart 
it  produces  slowing  of  the  rate  with  increased  amplitude  and  power  of  the  cardiac 
beat,  and  Serdzeff  has  proven  an  actual  increase  in  the  work  of  the  isolated  heart. 
Further,  the  rise  of  the  arterial  pressure  is  not  prevented  in  the  mammal  by  previ- 
ous section  of  the  splanchnic  nerve  or  of  the  spinal  cord  high  up  (Fellner).  Again, 
Cerna  found  that  the  slow  pulse  of  hydrastine-poisoning  occurs  after  section  of  the 


OXYTOCICS.  759 

pneumogastric  nerve  ;  also,  that  the  vagi  nerves  retain  their  power  up  to  the  fatal 
issue  ;  the  slow  pulse,  therefore,  is  not  of  inhibitory  origin.  That  the  vessels  are 
contracted  is  indicated  by  the  oncometrical  experiments  made  by  Marfori  upon  the 
dog's  kidney,  in  which  the  contraction  of  that  organ  was  found  to  be  a  constant 
phenomenon  of  the  early  stages  of  hydrastine-poisoning. 

It  is  probable  that  both  voluntary  and  involuntary  muscle-fibres  show 
the  primary  stimulating  influence  and  the  later  depressing  power  of  hy- 
drastine,  and  that  the  action  of  the  drug  upon  the  circulation  is  the  same 
as  that  upon  the  uterus  and  the  voluntary  muscles,  only  that  the  voluntary 
muscle-fibres  are  less  susceptible  to  its  action  than  are  those  of  involuntary 
life. 

Abdominal  Action. — It  is  probable  that  hydrastine  influences  both  the 
glands  and  muscular  fibres  of  the  alimentary  canal.  According  to  Cerna, 
it  markedly  increases  the  secretion  of  saliva  and  of  bile,  also  the  intestinal 
peristalsis. 

Uterus. — As  long  ago  as  1883  Schatz  called  attention  to  the  prac- 
tical value  of  hydrastis  in  all  forms  of  hemorrhage  from  the  womb,  assert- 
ing that,  though  the  drug  acts  well  in  cases  of  uterine  fibroids  or  myoma, 
it  is  also  efficacious  in  various  cases  of  menorrhagia,  dysmenorrhoea,  etc. 
These  results  have  been  confirmed  by  numerous  gynaecologists.  It  is, 
of  course,  not  possible  from  these  clinical  results  to  determine  whether  the 
good  is  obtained  by  an  action  of  the  drug  upon  the  uterine  mucous  mem- 
brane or  blood-vessels  or  by  provoking  contractions  of  the  uterine  walls. 
As  the  result,  however,  of  experiments  upon  the  lower  animals,  both 
Fellner  and  Slavatinski  affirm  that  hydrastine  has  a  distinct  ecbolic  action, 
causing  uterine  contractions  in  the  non-pregnant  uterus  and  abortion  in 
pregnant  rabbits.  Slavatinski  reports  a  case  of  premature  labor  produced  by 
hypodermic  injections  of  two  or  three  grammes  repeated  daily.  It  would 
seem,  therefore,  that  hydrastine  is  an  ecbolic,  and  that  it  arrests  uterine 
hemorrhage  in  part,  if  not  altogether,  by  provoking  muscular  contractions. 

Eyes. — Hydrastine  locally  applied  to  the  eye  causes  at  first  contrac- 
tion and  afterwards  dilatation  of  the  pupil  (Cerna). 

Absorption  and  Elimination. — Hydrastine  appears  to  be  absorbed 
from  the  alimentary  canal  somewhat  slowly  ;  at  least  it  is  stated  by 
Bunge  that  ten  times  as  much  of  it  is  required  to  kill  an  animal  when 
given  by  the  mouth  as  when  injected  hypodermically.  Marfori  states 
that  it  is  apt  to  have  a  cumulative  action  when  given  for  a  length  of 
time.  It  escapes  unchanged  through  the  kidneys,  and  has  also  been 
found  by  Hirschhausen  in  the  faeces. 

SUMMARY.— By  primarily  stimulating  the  spinal  motor  cord  hy- 
drastine causes  tetanic  convulsions,  -with  heightened  reflexes,  folio-wed, 
if  the  dose  have  been  large  enough,  by  loss  of  reflex  activity,  and  motor 
paralysis,  -which  are  probably  in  part  due  to  depression  of  the  motor 
centres,  and  are  certainly,  at  least  in  part,  the  outcome  of  depression 
of  the  motor  nerves  and  also  of  the  muscles  themselves.  According  to 
Cerna,  the  first  loss  of  reflex  activity  is  due  to  stimulation  of  Setsche- 


760  LOCAL    REMEDIES. 

now's  centre,  and  the  final  muscular  depression  is  preceded  by  excita- 
tion of  the  muscle-fibres.  Death  may  occur  in  a  convulsion  from  cramp- 
asphyxia,  or  [later  from  simultaneous  paralysis  of  the  respiratory 
centre  and  of  the  peripheral  apparatus.  The  arterial  pressure  is  first 
elevated  and  secondarily  depressed :  the  first  rise  of  pressure  is  proba- 
bly due  to  the  stimulation  of  the  heart-muscle,  increasing1  the  output  of 
force,  and  of  both  the  vaso-motor  centres  and  the  muscle-fibres  in  the 
arteriole  coats,  causing  contraction  of  the  blood-vessels :  the  fall  of 
pressure  is  the  result  of  a  direct  paralytic  action  exerted  upon  the 
muscle-fibres  in  the  heart  and  in  the  arterioles.  Hydrastine  notably 
increases  intestinal  peristalsis,  and  probably  uterine  contractions.  It 
•would  seem  to  be  a  universal  muscle-poison,  -which  acts  upon  both 
striated  and  non-striated  muscle-fibres  in  heart,  arterioles,  intestines, 
uterus,  and  generally  throughout  the  body ;  its  first  stimulant  action 
being  folio-wed  by  marked  depression. 

THERAPEUTICS. — When  locally  applied,  the  preparations  of  hydrastis 
have  a  very  remarkable  effect  upon  the  mucous  membranes.  They  have 
been  used  with  asserted  excellent  results  in  chronic  gastro-intestinal  ca- 
tarrhs, especially  those  due  to  alcoholic  excesses  :  as  Rutherford 13  found 
in  his  experiments  upon  the  lower  animals  that  the  hydrastin  of  com- 
merce caused  a  marked  increase  in  the  biliary  secretion,  it  is  probable 
that  in  these  catarrhs  spoken  of  the  good  result  is,  at  least  in  part,  due 
to  a  specific  influence  upon  the  liver  and,  it  may  be,  other  abdominal 
glands.  Nevertheless,  it  would  seem  certain  that  hydrastis  has  a  pecu- 
liar action  upon  mucous  membranes.  In  the  second  stages  of  gonor- 
rhoea, after  the  acute  inflammation  has  been  subdued,  injections  of  hydras- 
tin,  or  the  fluid  extract,  suspended  in  mucilage,  are  often  of  service.  Five 
grains  of  the  commercial  impure  hydrastin,  or  ten  to  twenty  minims  of 
the  fluid  extract,  may  be  used  to  the  ounce  of  fluid.  It  is  also  asserted 
by  various  specialists  that  in  otorrhcea,  nasal,  vaginal,  and  other  mucous 
catarrhs  the  remedy  is  locally  of  great  value.  In  dyspepsia  it  has  been 
used  as  a  stomachic  stimulant,  and  has  received  especial  praise  in  the 
vomiting  of  pregnancy.  At  present  it  is  not  known  to  which  of  the 
various  ingredients  of  commercial  hydrastin  these  local  effects  are  chiefly 
due,  so  that  either  the  hydrastin  or  a  preparation  of  hydrastis  is  prefera- 
ble to  the  pure  alkaloid.  These  preparations  are  a  tincture  (TiNCTURA 
HYDRASTIS — twenty  per  cent.,  U.  S. ),  the  dose  of  which  is  from  one  to 
two  fluidrachms  (4-7  C.c. );  a  fluid  extract  (FLUIDEXTRACTUM  HY- 
DRASTIS, U.  S. ),  dose,  from  one-half  to  one  fluidrachm  (2-4  C.c.);  and 
a  glycerite  (GLYCERITUM  HYDRASTIS,  U.  S. ),  dose,  from  one-half  to  one 
fluidrachm  (2-4  C.c.).  The  dose  of  commercial  hydrastin  is  five  to  ten 
grains.  For  internal  or  general  medication,  as  contrasted  with  the  local 
use  of  hydrastis,  the  alkaloid  or  its  salts  is  much  preferable  to  the  cruder 
preparation.  As  anti-hemorrhagic  or  ecbolic,  the  alkaloid  hydrastine 
(HYDRASTINA,  U.  S. )  may  be  used  in  doses  of  from  one-sixth  to  one- 
half  grain  (0.01-0.03  Gm.). 


OXYTOCICS.  761 

HYDRASTININ^E    HYDROCHLORAS— HYDRASTININE   HYDRO- 
CHLORATE.     U.  S. 

Hydrastinine  is  an  artificial  alkaloid  first  produced  by  Martin  Freund 
by  the  oxidation  of  hydrastine.  The  hydrochlorate  is  a  light  yellow 
crystalline  powder,  somewhat  deliquescent,  odorless,  having  a  bitter 
saline  taste,  soluble  in  o.  3  part  of  water  and  in  three  parts  of  alcohol. 

PHYSIOLOGICAL  ACTION. — For  our  knowledge  of  the  physiological 
action  of  hydrastinine  we  are  chiefly  indebted  to  Pius  Marfori,  P.  J. 
Archangelsky,  and  Kuno  von  Bunge.1  No  cases  of  poisoning  by  the 
drug  in  man  have  been  reported,  but  in  frogs  the  alkaloid  is  said  to 
produce  complete  paralysis  with  death  from  failure  of  respiration,  the 
heart  being  finally  arrested  in  systole  ;  whilst  in  mammals  it  causes  hy- 
peraesthesia,  general  tremors,  rapid  pulse,  and  dyspnoea,  followed  by 
paresis,  which  is  said  primarily  to  affect  the  front  legs  and  to  pass  into 
general  paralysis  with  dilated  pupils,  lowered  temperature,  and  death 
from  failure  of  respiration.  According  to  Bunge,  intestinal  peristalsis 
is  markedly  increased  by  hydrastinine. 

Nervous  System. — Our  present  knowledge  of  the  action  of  hydras- 
tinine upon  the  cerebrum  is  derived  from  experiments  upon  the  lower 
animals,  in  which  it  has  been  found  by  W.  Kiselew"  that  the  excitability 
of  the  motor  cerebral  cortex  progressively  decreases  with  progressively 
increasing  doses  of  hydrastinine,  although  it  never  entirely  disappears  ; 
and  that  the  white  substance  of  the  brain  is  affected  similarly  to  but  less 
powerfully  than  the  gray  matter.  Kiselew  has  also  confirmed  the  previ- 
ous observation  of  Tarchanoff,  that  the  alkaloid  arrests  or  greatly  dimin- 
ishes the  convulsive  attacks  in  epileptic  guinea-pigs.  It  is  further  worthy 
of  remark  that  Kiselew,  in  a  few  cases  of  human  epilepsy,  obtained  very 
favorable  results  from  the  administration  of  o.oi  to  0.03  gramme  of 
hydrastinine  four  times  a  day. 

So  far  as  the  lower  motor  apparatus  is  concerned,  the  chief  symptoms 
produced  by  hydrastinine  are  paralysis  with  loss  of  reflex  activity,  and 
also  lessening  of  the  general  sensibility.  It  seems  at  present  doubtful 
whether  there  is  or  is  not  an  early  stage  of  nervous  excitement,  since 
Archangelsky  affirms  that  there  is  increase  of  susceptibility  to  touch  and 
to  pain  in  the  frog  after  small  doses,  whilst  Marfori  states  that  there  is  no 
increase  of  the  reflex  activity  at  any  time.  If  there  be  any  stage  of 
excitement,  it  cannot  be  well  pronounced.  It  is  affirmed  that  hydras- 
tinine is  the  natural  antagonist  of  strychnine,  and  Marfori  asserts  that  the 
paralysis  is  of  purely  central  origin.  This,  however,  seems  to  be  in- 
correct, for  not  only,  as  Archangelsky  found,  is  the  excitability  of  the 
voluntary  muscle  lessened  by  the  toxic  dose  of  the  alkaloid,  but  Bunge 
has  shown  that  both  the  peripheral  nerves  and  the  muscle-fibres  were 
paralyzed  by  a  local  application  of  the  hydrastinine  solution. 

In  the  advanced  poisoning  the  respiratory  centre  seems  to  show  the 
depressing  influence  of  the  alkaloid,  and  hence  respiratory  failure  ;  but 
here  again,  according  to  Archangelsky,  especially  when  the  dose  has  not 
been  too  large,  there  is  a  period  of  primary  centric  stimulation. 


762  LOCAL    REMEDIES. 

Circulation. — The  elaborate  studies  of  Bunge  show  that  hydras- 
tinine  has  no  influence  upon  the  blood  itself,  but  all  observers  are  in 
accord  in  stating  that  the  blood-pressure  is  increased  by  the  large  dose 
of  the  alkaloid.  The  increase  appears  to  be  in  part  of  cardiac  and  in 
part  of  vascular  origin.  Thus,  both  Marfori  and  Bunge,  in  experi- 
ments made  with  the  Williams  apparatus,  found  that  the  systolic  impulse 
of  the  isolated  frog's  heart  becomes  abnormally  strong  under  the  influ- 
ence of  the  drug,  and  that  the  amount  of  the  heart's  work  is  distinctly 
increased.  A  second  cause  of  the  rise  of  the  arterial  pressure  is  asserted 
to  be  contraction  of  the  vessels,  which,  according  to  Marfori,  may  be- 
come so  great  as  entirely  to  arrest  the  renal  secretion.  As  the  result  of 
elaborate  experiments  made  with  section  of  the  splanchnics  and  of  the  spinal 
cord,  Archangelsky  reaches  the  conclusion  that  the  contraction  of  the 
vessels  is  chiefly  of  peripheral  origin,*  although  there  is  at  the  same  time 
some  stimulation  of  the  vaso-motor  centres  in  the  medulla, — a  conclusion 
concordant  with  Marfori' s  results.  When  the  amount  of  the  hydrastinine 
has  not  been  too  large,  the  elevated  arterial  pressure  gradually  returns 
to  the  normal  (Bunge)  ;  but  after  a  fatal  dose  of  the  alkaloid  a  pro- 
nounced fall  of  pressure  finally  comes  on,  apparently  as  the  result  of  the 
paralysis  of  progressive  asphyxia,  since  artificial  respiration  will  bring 
back  the  pressure  to  the  normal  (Marfori):  further,  it  is  asserted  by 
various  observers  that  the  heart  is  finally  arrested  in  systole,  so  that  it 
would  seem  that  hydrastinine  differs  from  hydrastine  in  not  being  a 
cardiac  paralyzant  in  any  dose. 

Pupils. — Archangelsky  has  noted  that  one  to  two  drops  of  the  ten 
per  cent,  solution  of  a  salt  of  hydrastinine  in  the  eye  will  produce  a  dila- 
tation of  the  pupil,  which  reaches  its  maximum  in  two  to  three  hours,  and 
remains  twelve  to  fifteen  hours. 

Uterus. — The  effect  of  hydrastinine  upon  the  uterus  was  studied  in 
pregnant  and  puerperal  dogs,  cats,  and  rats  by  Archangelsky,  who 
found  that  it  produced  rhythmic  contractions,  independent  of  any  vaso- 
motor  influences,  apparently  by  stimulation  of  the  uterine  walls.  On 
the  other  hand,  Bunge,  having  failed  in  two  experiments  to  provoke 
abortion  or  uterine  contractions  in  pregnant  animals  by  large  or  even  fatal 
doses  of  the  alkaloid,  affirms  that  it  is  not  an  ecbolic.  Nevertheless, 
Faber,15  as  the  result  of  a  number  of  trials,  states  that  hydrastinine  given 
hypodermically  during  human  labor  very  notably  increases  the  force  and 
length  of  the  uterine  contractions,  causing  a  spasm  which  affects  all 
portions  of  the  uterus,  and  which  is  similar  in  character  to  that  provoked 
by  ergot.  In  some  of  the  cases  there  was  uterine  tetanus,  lasting  as  long 
as  fifteen  minutes.  Faber  also  asserts  that  distinct  contractions  can  be 
produced  in  the  unimpregnated  womb. 

*  The  assertion  of  Bunge,  that  because  in  heavily  chloralized  animals  hydrastinine 
fails  to  elevate  the  pressure,  therefore  it  acts  chiefly  upon  the  vaso-motor  centre,  is  a  non 
stqttitur,  as  chloral  acts  upon  the  whole  circulatory  apparatus.  Moreover,  Bunge's  own 
experiments  show  that  the  alkaloid  lessens  the  size  of  the  spleen  by  contracting  the 
blood-vessels. 


OXYTOCICS.  763 

Absorption. — Bunge  has  found  that  hydrastinine  is  readily  absorbed 
and  eliminated  unchanged,  chiefly  with  the  urine,  but  also  to  some 
extent  with  the  saliva,  bile,  and  intestinal  secretions.  It  did  not  appear 
to  increase  the  amount  of  bile  secreted. 

SUMMARY. — Hydrastinine  in  sufficient  dose  appears  to  be  a  pow- 
erful depressant  to  the  -whole  motor  tract,  commencing-  in  the  motor 
area  of  the  cerebral  cortex  and  ending  in  the  muscle, — motor  brain, 
motor  cord,  motor  nerve,  and  muscle  being  all  more  or  less  affected. 
"Whether  this  depression  be  or  be  not  everywhere  preceded  by  a  brief 
stage  of  excitement  is  at  present  somewhat  uncertain,  but  it  is  ex- 
tremely probable  that  there  is  a  primary  stimulation,  at  least,  of  the 
muscles.  It  is  a  stimulant  to  the  circulation;  the  heart  under  its  in- 
fluence acts  more  slowly,  but  more  powerfully,  and  is  in  fatal  poison- 
ing finally  arrested  in  systole,  -whilst  the  blood-vessels  undergo 
powerful  contractions  until  late  in  the  poisoning;  the  vascular  con- 
tractions are  probably  the  result  of  stimulation  both  of  the  vaso- 
motor  centres  and  of  the  muscle  in  the  -walls  of  the  arterioles.  The 
final  fall  of  arterial  pressure  is  asserted  to  be  the  result  of  the  as- 
phyxia, and  not  produced  directly  by  the  drug.  Although  it  is  denied 
by  some,  hydrastinine  appears  to  be  a  powerful  oxytocic,  and  it  is 
probable  that  its  action  upon  the  heart,  the  arterioles,  the  uterus,  the 
intestines,  and  the  skeletal  muscles  is  the  outcome  of  a  wide-spread 
general  muscular  stimulation. 

THERAPEUTICS. — Hydrastinine  is  used  in  medicine  chiefly  for  those 
complaints  for  which  it  was  originally  recommended  by  Falck, — namely, 
menorrhagia,  metrorrhagia,  congestive  dysmenorrhcea,  and  even  endo- 
metritis.  The  testimony  in  favor  of  its  arresting  uterine  hemorrhage  in 
all  forms  is,  on  the  whole,  very  consistent,  and  is  abundant,  but  it  is 
also  believed  by  many  gynaecologists  to  have  some  alterative  influence 
upon  the  mucous  membrane  of  the  uterus.  It  is  affirmed  by  some  gynae- 
cologists, but  denied  by  others,  that  it  is  an  active  oxytocic,  and  exerts 
its  influence  upon  impregnated  and  unimpregnated  wombs  largely  by 
causing  muscular  contractions.  It  will  be  seen  that  the  range  of  its  useful- 
ness in  gyneecology  is  entirely  similar  to  that  of  hydrastine  ;  it  has,  how- 
ever, acquired  popular  favor  more  rapidly  and  decidedly  than  the  natural 
alkaloid.  It  may  possibly  be  more  effective  as  an  ecbolic,  but  its  supe- 
riority probably  lies  in  chief  part  in  its  being  distinctly  less  toxic  and  pro- 
ducing cardiac  stimulation  rather  than  cardiac  depression.  When  an 
immediate  impression  is  desired,  the  sulphate  should  be  given  hypoder- 
mically.  When  a  prolonged  continuous  action  is  required,  it  may  be 
administered  by  the  mouth.  The  results  obtained  by  Kiselew  demand  a 
fair  trial  of  it  in  epilepsy.  Hydrastinine  has  some  value  as  a  subsidiary 
cardiac  tonic;  it  does  not  belong  in  the  same  class  as  digitalis,  but  its 
tonic  influence  is  often  decidedly  helped  by  its  cardiac  action.  Dose, 
three-quarters  of  a  grain  to  a  grain  and  a  half  (0.05-0.  i  Gm. ). 

GOSSYPII  CORTEX.  U.  S. — The  root  of  the  ordinary  cotton-plant,  the  Gos- 
sypium  herbaceum,  is  said  to  be  used  by  the  negroes  in  various  portions  of  the 


764 


LOCAL   REMEDIES. 


South  as  an  abortifacient,  and  Bouchelle,  as  long  ago  as  1841,  affirmed  that  it  has 
medical  properties  similar  to  those  of  ergot.  It  has  not,  however,  come  into  gen- 
eral use,  and  our  knowledge  of  its  properties  is  very  scanty  and  uncertain.  In  the 
experiments  of  I.  C.  Martin1  enormous  doses  produced  heaviness  and  stupor  in 
both  frogs  and  mammals,  but  did  not  cause  abortion  in  pregnant  guinea-pigs  or 
rabbits :  On  the  contrary,  Mohr 2  produced  abortion  in  a  cat  with  three  doses  of 
20  C.c.  each  of  the  fluid  extract.  H.  I.  Garrigues3  has  found  cotton-root  a  service- 
able agent  in  arresting  hemorrhage  and  ameliorating  the  other  symptoms  of  uterine 
polypoid  and  fibroid  tumors,  and  even  of  uterine  cancer.  He  insists  that  the  com- 
mercial fluid  extract  is  inert  and  the  decoction  must  be  freshly  prepared.  The 
oxytocic  dose  of  a  decoction  (four  ounces  in  a  quart  of  water  boiled  to  a  pint)  is 
stated  to  be  a  wineglassful,  to  be  repeated  every  thirty  minutes  as  necessary.  The 
remedy  has  also  been  employed  in  amenorrhcca  and  in  dysinenorrhcea,  in  which 
diseases  from  three  to  five  grains  of  a  solid  aqueous  extract  have  been  given  three 
times  a  day.  The  fluid  extract  may  be  used  in  doses  of  a  fluidrachm  (3.7  C.c.). 
Absorbent  Cotton  (GOSSYPIUM  PURIFICATUM,  U.  S. )  is  ordinary  cotton  wool 
deprived  of  impurities  and  fatty  matters.  It  is  used  mechanically,  and  as  an 
absorbent. 


ERGOT. 

1.  TULASNE    ....  Ann.    des    Sciences    Nat., 

Botan.,  1853,  35.,  xx. 

2.  JACOBI A.   E.  P.    P.,   1897,   xxxix. 

85- 

3.  ROBERT A.  E.  P.  P.,  1884,  xviii.  316. 

4.  OLDRIGHT  ....  Canada  Med.  Journ.,  1870, 

404. 

5.  WRIGHT Ed.  M.  S.  J.,  Oct.  1839,  lii. 

6.  KERSCH Betz's  Memorabilien,  xviii. 

7.  HAUDELIN  .  .   .  .  S.  Jb.,  civ. 

8.  BAILLY  and  SEE  .  B.  G.  T.,  Ixxviii.  435. 

9.  HOLMES A.  de  P.,  1870.  iii. 

10.  KOHLER  and  EBERTY  .  V.  A.  P.  A.,  Ix.  384. 
n.  WOOD P.  M.  T.,  1874,  iv.  518. 

12.  WERNICH    .   .   .  .  V.  A.  P.  A.,  1872,  Ivi.  510. 

13.  PETON De    1'Action    de    1'Ergot, 

Paris,  1878. 

14.  RINGER  and  SAINSBURV  .  B.  M.  J.,  Jan.  1884. 

15.  VOGT B.  K.  W.,  1869,  No.  12. 

16.  BOREISCHA    .   .   .  Arb.  Pharmak.  Lab.  Mos- 

kau,  i.  55. 

17.  BROWN-SEQUARD  .  A.  de  P.,  1870,  iii.  434. 

18.  WERTHEIMER  and  MAGNIN  .  A.  de  P.,  1892, 

5  s.,  iv.  92. 

19.  BODIN Journ.  des  Connaissances 

Med.,  1842. 

20.  DA  COSTA  .   .   .   .  A.  J.  M.  S.,  Jan.  1875. 

21.  LANGENBECK    .   .  B.  K.  W.,  1869,  vi. 

22.  BAR  LAN- FONTA  YR  AL  .  Journ.  des  Sci.  Med.- 

pratiques  de  Montpellier, 
vi.,  vii. 

23.  LUTON G.  H.  M.  C.,  Oct.  1871. 

24.  S.  Jb.,  Dec.  1871;  Lancet, 

1876,  ii.  409. 

25.  LE  GENDRE  .   .   .  B.  G.  T.,  Ixxvii.  282. 

26.  POYET  and  COMMARMOND  .  Ann.  de  la  Soc. 

de  Med.  de  Saint-Etienne 
et  de  la  Loire,  1863. 

27.  DAVIS J.  A.  M.  A.,  1884. 

28.  SUNOL L.  M.  R.,  1884. 


29.  KELLY 

30.  DEHENNE   .  .   . 

31.  HlLDEBRANDT  . 

32.  MEADOWS  .   .   . 

33.  GOODELL      .    .    . 

34.  HEUSINGER   .   . 

35.  GRUNFELD.   .  . 

36.  KOHLER  .   .   .   . 

37.  SCHULLER  .   .   . 

38.  BOLDT    .... 

39.  PLUMIER  ... 

40.  SOLLMANN  and 

41.  HEMMETER    . 

42.  EBERTY    .  .  . 


.  Med.  Register,  1887. 

.  Munich  Med.,  xlv.  86. 

.  B.  K.  W.,  June  17,  1872. 

.  Pract.,  i.  166. 

.  Proc.  Med.  Soc.  of  Penn- 
sylvania, 1873. 

.  Journ.  fur  Pharmakod.,  i. 
405- 

.  In.  Dis.,  Dorpat,  1892. 

.  V.  A.  P.  A.,  Ix. 

.  B.  K.  W.,  1874,  304- 

.  S.  Jb.,  March,  1872. 

.  J.  de  P.  P.,  1905,  vii.  13. 

BROWN  .  J.   A.  M.  A.,   1905, 
xlv.  229. 

.  M.  News,  1891,  Ivii. 
.  In.  Dis.  Halle,  1873. 


HYDRASTIS. 

BUNGE In.  Dis.,  Dorpat,  1893. 

FRIEDEBERG    .  .  S.  Jb.,  Bd.  278. 

FALCK  and  GUENSTE  .  V.  A.  P.  A.,  1890,  cxix. 

MOSSE  and  TAUTZ  .  Z.  K.  M.,  xliii. 

CURCI L.  M.  R.,Oct.  ii,  1886. 

MARFORI    .   .   .   .  A.  E.  P.  P.,  xxvii. 
PHILLIPS  and  PF.MBREY  .  J.  P.,  1897,  xxi. 
DE  Vos Presse  M.  B.,  1895,  xlvii. 


o.  FELLNER    .   .   . 
i.  SERDZEFF  .   .   . 
2.  BARTHOLOW  .   . 

3.  RUTHERFORD  . 
4.  KISELEW    .   .   . 
•;.  FABF.R  . 

.  Wien.  Med.  Jahrb.,  1885. 
.  In.  Dis.,  Moscow,  1890. 
.  Lloyd's   Drugs  and   Med 
of  North  America. 
.  B.  M.  J.,  1879,  i.,ii. 
.  S.  Jb.,  ccxxxviii. 
.  Th.  M.,  1892,  vii. 

GOSSYPII   CORTEX. 


1.  MARTIN    .  . 

2.  MOHR    .  . 

3.  GARRIGUES 


.  A.  J.  M.  S.,  Jan.  1882. 
.  Ther.  Geg.  1905,  vii.  360. 
.  Quart.  Bull.  Clin.  Soc..N. 
Y.,  Jan.  1887. 


FAMILY  IX.— IRRITANTS  AND   COUNTER- 
IRRITANTS. 


IRRITANTS. 

In  the  treatment  of  diseases  of  the  skin  various  irritating  substances  are 
used  for  the  purpose  of  stimulating  the  nutritive  activity  of  the  diseased 
part.  The  most  important  of  these  drugs  are  noticed  at  this  place. 

Under  the  name  of  Sapo  the  U.  S.  Pharmacopcea  recognizes  ordinary 
white  castile  soap,  a  combination  made  between  olive  oil  and  soda,  and 
consisting  chiefly  of  a  mixture  of  sodium,  oleate  and  palmitate.  This 
soap  is  entirely  free  from  irritant  properties,  and  is  used  externally  as  a 
detergent  and  sometimes  internally  in  combination  with  laxatives  to  ren- 
der their  action  milder  and  perhaps  more  effective. 

SAPO  MOLLIS,  U.  S. ,  formerly  known  officially  as  Sapo  Viridis,  Soft 
soap,  or  Green  soap,  is  made  by  the  action  of  caustic  potash  upon  linseed 
oil ;  more  potash  being  used  than  is  necessary  for  the  neutralization  of  the 
fatty  acids,  so  that  the  resulting  combination  is  not  only  strongly  deter- 
gent but  also  irritant,  and  even  mildly  caustic.  Formerly,  when  vege- 
table oils  contained  much  chlorophyll,  this  soap  had  a  distinct  greenish 
color,  but  as  now  prepared  it  is  a  brownish  or  yellowish  semifluid  mass, 
which  yields  a  nearly  clear  solution  with  five  times  its  weight  of  hot 
water.  It  is  used  chiefly  in  the  treatment  of  eczema.  It  destroys  fatty 
matter  rapidly,  softens  down  exudation,  and  markedly  affects  the  nutrition 
of  the  skin. 

CHRYSAROBINUM.  U.  S.  Chrysarobin. — Under  the  name  of  Goa 
Powder,  Araroba  or  Chrysaroba,  certain  powders  varying  from  fine  to 
coarse  and  from  light  yellow  to  dark  chocolate,  have  long  been  used  in 
Brazil  and  the  East  Indies.  Formerly  supposed  to  be  the  product  of 
certain  lichens,  they  are  now  known  to  be  obtained  from  irregular  inter- 
spaces in  the  wood  of  the  Andira  Araroba,  a  large  Brazilian  tree.  Goa 
powder  depends  for  its  activity  upon  chrysarobin.  The  percentage  of 
chrysarobin  in  the  goa  powder  varies  so  much  that  the  crude  drug  is  not 
recognized  in  the  U.  S.  Pharmacopcea. 

Chrysarobin  *  is  an  odorless,  tasteless  powder,  when  first  obtained  of 
a  pale  orange  color,  but  darkening  on  exposure.  It  is  very  slightly 
soluble  in  cold  water  or  alcohol,  but  is  freely  soluble  in  alkaline  solutions 
and  in  hot  fats  ;  formerly  supposed  to  be  identical  with  chrysophanic 


"Chrysarobin  must  not  be  confounded  with  anthrarobin,  a  distinct  substance  pro- 
duced by  Liebermann  from  alizarin  (Ber.  d.  Chent.  Ges.,  1888),  which  Weyl  (Arch.  f.  d. 
Ges.  Phys.,  1888,  xliii.)  has  proved  to  be  free  from  poisonous  properties. 

765 


766  LOCAL    REMEDIES. 

acid,  chrysarobin  is  now  known  to  be  a  distinct  neutral  principle.  When 
taken  internally  in  doses  of  from  six  to  eight  grains,  it  produces  in  about 
four  hours  repeated  vomiting,  sometimes  followed  by  purging  (I.  A. 
Thompson7),  and  it  has  been  shown  by  Weyl  to  be  an  active  irritant 
poison. 

Chrysarobin  is  never  used  internally,  but  as  a  local  application  in 
various  skin  diseases  when  there  is  a  tendency  to  excess  of  dry  exudation, 
being  especially  effective  in  psoriasis. 

COUNTER-IRRITANTS. 

Almost  from  time  immemorial  physicians  have  believed  that  morbid 
processes  in  deep-seated  or  superficial  organs  could  be  modified  by  irrita- 
tions artificially  induced  in  distant  parts.  To  the  drugs  used  for  producing 
these  remedial  irritations  the  name  of  revulsants,  or  counter-irritants,  has 
been  given,  the  process  being  called  revulsion,  or  counter-irritation. 

The  question  as  to  the  manner  in  which  a  counter-irritant  acts  is 
essentially  distinct  from  the  question  whether  it  does  or  does  not  act. 
However  crude  and  uncertain  our  theories  may  be,  clinical  experience 
has  demonstrated  the  value  of  counter-irritants  in  various  internal  condi- 
tions. It  is  proved  beyond  cavil  that  internal  morbid  processes  may  at 
times  be  relieved  by  creating  external  irritations. 

Our  present  explanations  of  the  way  in  which  counter-irritants  act 
are  certainly  not  satisfactory.  There  are  abundant  physiological  proofs 
demonstrating  the  connection  between  distant  organs  having  no  appar- 
ent anatomical  connection  ;  such  is  the  relation  between  the  mammary 
glands  and  the  uterus  ;  such  are  the  phenomena  of  so-called  metastasis 
seen  in  mumps,  gout,  and  other  constitutional  disorders,  in  which  the 
development  of  a  new  irritation  is  accompanied  by  the  disappearance  of 
one  already  existing.  Familiar  examples,  also,  may  be  found  in  the 
paraplegias  sometimes  produced  by  irritation  of  a  renal  calculus,  in  the 
headache  of  gastric  irritation,  in  the  shoulder-pain  of  diseased  liver,  and 
in  the  amaurosis  or  epileptiform  attacks  sometimes  caused  by  a  decayed 
tooth.  In  the  well-known  experiment  of  Brown-Sequard  it  was  found 
that  if  one  sciatic  nerve  of  the  guinea-pig  be  cut  epileptic  attacks  may 
be  produced  by  gently  rubbing  the  back  of  the  ear  upon  the  same  side. 

One  commonly  offered  explanation  of  counter-irritation  is  that  there 
is  only  a  certain  amount  of  blood  and  of  nervous  energy  in  the  body, 
and  that  if  the  blood  or  the  nervous  energy  be  drawn  to  one  part  there 
must  be  less  in  another  part.  Surely,  however,  the  amount  of  blood 
drawn  to  the  skin  by  a  mustard  plaster  is  too  small  sensibly  to  affect  the 
general  mass  in  the  body.  It  is  more  probable  that  the  phenomena  of 
counter-irritation  are  the  result  of  reflex  disturbances  of  the  vaso-motor 
nerves  which  influence  the  size  of  the  blood-vessels,  or  of  the  trophic 
nerves  which  directly  affect  nutrition. 

It  is  of  great  practical  importance  to  know  where  the  counter-irritant 
should  be  placed  to  affect  most  powerfully  any  given  internal  organ. 


COUNTER-IRRITANTS.  767 

We  have  no  thoroughly  scientific  experimental  knowledge  as  to  this 
matter,  but  it  has  been  clinically  demonstrated  that  the  general  law  for 
deep-seated  parts  is  that  the  revulsant  should  be  put  directly  over  the 
part.  When  a  superficial  action  is  desired,  other  directions  are  needed. 
We  are  indebted  to  Anstie  for  pointing  out  what  appears  to  be  a  law,  or 
at  least  a  good  working  rule  for  practice, — namely,  that  when  a  superficial 
part  supplied  by  the  anterior  branches  of  a  spinal  nerve  is  to  be  affected, 
the  counter-irritant  should  be  placed  over  the  posterior  roots  of  the  nerve. 
Not  only  can  obstinate  neuralgia  often  be  relieved  by  this  reflex  action, 
but  also  the  inflammatory  changes  so  often  coincident  with  intercostal 
neuralgia.  The  law  seems  also  to  apply  to  cervical  nerves,  since  the 
proper  position  for  the  blister  in  trigeminal  neuralgia  is  back  of  the  ear 
or  on  the  nape  of  the  neck.* 

For  the  purposes  of  study,  counter-irritants  are  conveniently  arranged 
under  two  heads  :  first,  those  which  do  not  provoke  decided  alteration0 
of  the  dermal  structure,  but  simply  cause  an  irritation  which  soon  passes 
away  ;  these  are  the  Rubefacients :  second,  counter-irritants  which  pro- 
duce severe  structural  alterations  ;  in  this  class  belong  the  hot  iron,  the 
issue,  the  seton,  and  other  destructive  appliances,  and  also  the  epispastics, 
vesicatories,  or  more  colloquially  blisters,  which  are  used  to  produce  that 
peculiar  inflammation  of  the  cuticle  with  an  outpouring  of  serum  commonly 
known  as  the  blister. 

In  choosing  between  a  rubefacient  and  a  blister,  the  physician  is 
guided  by  the  character  of  the  disease  present  in  the  subject.  A  rube- 
facient causes  a  wide-spread,  intense  but  temporary,  irritation  and  con- 
gestion of  the  part, — an  irritation  which  for  the  moment  produces  a  strong 
influence,  but  leaves  no  permanent  impression  upon  the  nutritive  acts  of 
the  diseased  organ.  A  rubefacient  is  to  be  employed  when  the  disease 
is  functional, — when  there  is  only  a  nervous  disturbance  or  a  congestion 
to  be  dealt  with  ;  whereas  the  blister  is  useful  when  inflammation  has 
produced  permanent  change.  Very  frequently  in  inflammatory  condi- 
tions, however,  rubefacients  are  useful  to  relieve  accompanying  con- 
gestion. Thus,  in  a  pneumonia  the  rubefacient  may  have  no  effect 
upon  the  focus  of  the  disease,  but  may  be  very  serviceable  in  checking 
a  wide-spread  collateral  congestion. 

To  the  careful  use  of  rubefacients  there  are  scarcely  any  contra- 
indications ;  some  caution  is,  however,  necessary  in  their  application. 
A  severe  internal  irritation  may  so  successfully  counter-irritate  against 
the  external  counter-irritation  that  the  latter  has  for  the  time  being  no  ap- 
parent effect,  and  yet  really  exerts  a  disorganizing  influence.  Thus,  a 
mustard  plaster,  under  the  circumstances  named,  may  at  the  time  of  its 
application  produce  no  pain  or  redness,  and  yet  twenty-four  hours  after- 

*  The  statement  of  A.  Dumontpallier  (Gaz.  Hebdomadaire,  November,  1879),  that 
the  best  results  of  counter-irritation  are  obtained  by  applying  the  counter-irritant  upon 
the  opposite  side  of  the  body,  so  as  to  be  exactly  symmetrical  with  the  diseased  part, 
has  never  to  our  knowledge  been  confirmed. 


768  LOCAL    REMEDIES. 

wards  disorganizing  inflammation  may  set  in  at  the  seat  of  the  applica- 
tion. When  there  is  severe  internal  irritation  the  counter-irritant  should 
always  be  removed  when  it  has  been  applied  long  enough  to  endanger 
violent  local  effects,  even  though  it  has  exerted  no  sensible  influence. 

There  is  one  use  of  rubefacients  which  is  not  that  of  counter-irritation, 
but  which  is  often  of  practical  importance.  An  irritation  of  the  sensitive 
nerve  in  the  normal  animal  produces  an  immediate  vaso-motor  spasm, 
and  in  certain  conditions  of  the  body  irritation  of  the  mucous  membrane 
or  of  the  skin  is  of  great  service  in  stimulating  respiration  or  circulation. 
In  a  true  exhaustion  rubefacients  are  of  very  little  value,  for  the  only 
possible  source  of  absolute  increase  of  power  to  the  system  is  in  food  ; 
and  in  exhaustion  those  stimulants  should  be  employed  which  increase 
the  power  of  assimilating  food.  For  this  reason,  external  irritants  are 
useful  as  stimulants  in  conditions  of  depression  rather  than  of  exhaustion. 
Especially  are  they  valuable  when  there  is  wide-spread  loss  of  functional 
activity  in  the  vaso-motor  system.  Such  conditions  of  depression,  with 
vaso-motor  weakness,  exist  in  acute  collapse  from  any  cause,  in  shock 
following  injuries,  in  the  first  stage  of  pernicious  malarial  fever,  and  in 
other  cases  when  the  powers  of  the  system  are  seemingly  overwhelmed 
by  some  depressing  agency. 

Blisters  are  especially  useful  in  inflammations  of  serous  membranes, 
such  as  pleuriti s  and  peritonitis  ;  are  very  strongly  recommended  by  some 
practitioners  in  parenchymatous  inflammations,  such  as  pneumonia  ;  and 
may  be  of  service  in  persistent  forms  of  nervous  irritation,  such  as  the 
maniacal  delirium  of  fevers,  when  dependent  upon  the  irritant  action  of  a 
blood-poison,  and  not  upon  exhaustion.  The  amount  of  serum  which  is 
poured  out  from  a  blister  is  sometimes  quite  large,  and  vesicants  have 
even  been  employed  to  relieve  dropsy.  In  general  dropsy  their  use  is 
simply  unjustifiable  ;  but  in  local  dropsies,  as,  for  example,  serous  effusion 
into  the  pleural  sac  or  into  the  pericardium,  dependent  upon  local  inflam- 
mation, they  often  do  good,  not  only  by  affecting  favorably  the  disease- 
process,  but  also  by  hastening  the  removal  of  the  effusion. 

In  some  chronic  affections,  long-continued  severe  counter-irritation  is 
required  :  in  such  cases  a  blister  may  be  "kept  open"  by  the  use  of 
stimulating  ointments,  such  as  the  mezereon  ointment.  In  chronic  in- 
flammation of  the  joints,  repeated  blistering  is  very  often  of  service. 
When  the  inflammatory  action  is  rheumatic,  in  our  experience  better 
results  are  obtained  by  repeated  blistering  than  by  keeping  a  blister 
sore  by  means  of  irritants.  In  neuritis,  whether  rheumatic  or  other- 
wise, blisters  are  often  of  service  :  they  should  be  applied  as  a  long 
narrow  strip  along  the  course  of  the  nerve.  In  obstinate  local  neural- 
gia, very  mild  blistering  over  the  seat  of  pain,  or  in  accordance  with 
Anstie's  law,  is  sometimes  advantageous. 

The  contra-indications  to  the  use  of  blisters  are  high  arterial  and 
febrile  excitement  and  a  decided  want  of  vital  power.  In  the  former 
case,  the  irritating  influence  which  they  exert  upon  the  general  system 


COUNTER-IRRITANTS.  769 

may  increase  the  constitutional  disturbance  to  such  an  extent  as  to  do 
more  injury  than  any  local  benefit  derived  from  them  can  do  good. 
When  the  vitality  is  very  low,  blisters  may  give  rise  to  sloughing 
ulcers,  which,  refusing  to  heal,  may  waste  very  seriously  the  already 
exhausted  system.  Hence,  in  all  acute  diseases  of  such  type  that  the 
nutritive  forces  are  exceedingly  depressed,  blisters  must  be  avoided,  or 
be  used  only  with  great  caution.  For  the  same  reason,  great  care 
must  be  exercised  in  their  employment  in  the  very  young  or  the  very 
aged.  Very  rarely  indeed  is  a  blister  called  for  in  the  case  of  a  young 
infant,  and  if  it  be  employed  at  all,  it  should  be  allowed  to  remain  in  con- 
tact with  the  skin  only  long  enough  to  produce  slight  pain  or  redness,  and 
the  complete  vesication  should  be  obtained  by  the  after-use  of  a  poultice. 
The  hot  iron  or  other  destructive  counter-irritant  is  to  be  used  only  in 
cases  of  continuing  chronic  disease  with  structural  lesion.  At  present, 
neither  the  moxa  nor  the  issue  is  ever  employed  in  civilized  countries  ; 
the  seton  with  extreme  rareness.  The  actual  cautery,  however,  affords 
a  valuable  method  of  treating  chronic  neuritis,  chronic  meningitis,  cere- 
bral or  spinal,  and  various  forms  of  chronic  arthritis. 

EPISPASTICS. 

There  are  various  substances  which  are  capable  of  producing  vesica- 
tion, but  the  only  one  in  ordinary  use  is  cantharides.  .In  cases  of  emer- 
gency ammonia  is  sometimes  employed.  (See  page  281.) 

CANTHARIS— CANTHARIDES.     U.S. 

The  dried  bodies  of  the  Cantharis  vesicatoria,  a  beetle  inhabiting 
Southern  Europe.  Spanish  flies  are  from  half  an  inch  to  nearly  an  inch 
in  length  and  two  to  three  lines  in  breadth,  and  have  a  large  heart- 
shaped  head  and  brilliant  metallic-green  elytra,  or  wing-cases.  Their 
odor  during  life  is  very  strong  and  fetid,  but  is  almost  entirely  lost  in 
drying  ;  their  taste  is  urinous,  very  burning,  and  acrid.  When  ground, 
Spanish  flies  afford  a  grayish-brown  powder,  full  of  minute  greenish 
spangles,  the  remains  of  the  feet,  head,  and  wing-cases.  The  active 
principle  of  cantharides  is  Cantharidin,  which  occurs  in  white  crystalline 
scales,  is  inodorous,  tasteless,  insoluble  in  water,  nearly  so  in  cold 
alcohol ;  soluble  in  ether,  benzole,  the  oils,  and  very  freely  so  in  chloro- 
form. Notwithstanding  the  insolubility  of  pure  cantharidin,  Spanish  flies 
yield  their  virtues  to  alcohol  and  to  water. 

Local  Action. — Absorption  and  Elimination. — Cantharides  is  very 
irritating,  and,  when  applied  to  the  skin,  causes  at  first  redness,  with 
burning,  then  free  vesication  and  severe  pain,  and,  if  the  contact  be 
longer  maintained,  deep  inflammation  and  sloughing.  Upon  the  mucous 
membranes  it  produces  a  no  less  intense  effect.  The  cantharidin  is 
rapidly  absorbed,  and  is  eliminated  unchanged  by  the  kidneys. 

General  Action. — The  first  symptom  produced  by  the  small  dose  of 

49 


770  LOCAL   REMEDIES. 

cantharides  is  burning  in  the  genito-urinary  passages.  After  the  ingestion 
of  ten  minims  of  the  tincture  the  irritation  may  amount  to  complete  stran- 
gury. The  toxic  dose  produces  in  a  very  few  minutes  burning  in  the 
pharynx  and  oesophagus  and  a  sense  of  stricture  in  the  throat.  The 
pain  soon  spreads  to  the  stomach,  and  vomiting  comes  on.  The  symp- 
toms rapidly  increase  in  severity  ;  the  abdominal  pain  becomes  very 
severe,  and  in  the  majority  of  cases  purging  takes  place.  The  matters 
rejected  by  the  stomach  are  first  mucous  (with,  if  the  drug  have  been 
taken  in  powder,  little  greenish  specks  through  them),  then  bilious,  and 
finally  bloody.  The  stools  are  mucous,  then  fibrinous,  bloody,  becoming 
often  very  scanty,  but  excessively  numerous,  and  in  their  passage  accom- 
panied by  great  tenesmus.  Probably  in  most  cases,  early  in  the  poi- 
soning severe  salivation  is  developed,  and  is  frequently  accompanied  by 
great  swelling  of  the  salivary  glands.  Sometimes  death  occurs  in  a  very 
short  time,  from  collapse  produced  by  the  intense  gastro-intestinal  inflam- 
mation ;  but  more  generally  it  is  postponed  for  some  hours,  and  a  new 
train  of  symptoms  arises.  Aching  pains  in  the  back  and  very  frequent 
micturition  indicate  the  commencing  urino-genital  irritation.  These 
symptoms  increase  in  intensity  until  there  is  a  constant,  irresistible  desire 
to  urinate,  with  violent  tenesmus  of  the  bladder,  and  yet  an  inability  to 
pass  more  than  a  few  drops  of  urine,  which  is  albuminous,  and  not  rarely 
bloody.  In  some  cases  there  is  a  violent  erotic  excitement,  an  unquench- 
able lust,  accompanied  in  man  by  numerous  seminal  emissions  ;  *  violent 
priapism,  swelling  and  heat  of  the  organs,  and  even  severe  inflammation  of 
the  parts  may  indicate  the  intensity  of  the  local  action  of  the  poison ;  some- 
times gangrene  ultimately  occurs.  Consciousness  and  general  power  are 
often  long  preserved  when  the  local  symptoms  and  agony  are  intense, 
but,  if  the  dose  have  been  large  enough,  sooner  or  later  collapse  comes 
on,  with  the  usual  accompaniments,  and  the  prostration  deepens  into 
complete  powerlessness,  stupor,  coma,  and  finally  death.  In  some  cases 
violent  hydrophobic  delirium  and  severe  tetanic  convulsions  are  said  to 
have  occurred  (Tardieu).  Paraplegia  has 'been  noticed  in  several  cases 
by  Palle1  : l  it  was  probably  reflex  in  its  origin,  and  due  to  the  intense 
irritation  of  the  genito-urinary  organs. 

In  animals,  cantharides  produces  very  much  the  same  symptoms  as  it  does  in 
man.  In  dogs,  according  to  the  experiments  of  Orfila  and  of  Beaupoil,  the  symptoms 
of  gastro-intestinal  inflammation  are  more  prominent  than  those  of  irritation  of  the 
genito-urinary  tract.  It  has  been  asserted  that  the  lack  of  erotic  excitement  in 
these  cases  shows  that  the  medicine  acts  differently  upon  man  and  upon  animals. 
As  already  stated,  however,  erotic  delirium  is  very  often  absent  in  fatal  poison- 
ing in  man,  while  Schroff  states  that  ten  drops  of  the  tincture  of  cantharides  will 
frequently  produce  great  sexual  excitement  in  man,  and  the  whole  drift  of  the  evi- 
dence is  that  libidinous  desires  are  much  more  apt  to  be  caused  by  amounts  ot 
Spanish  flies  but  slightly  toxic  than  by  fatal  doses.  Indeed,  the  irritation  caused 
by  the  latter  would  seem  to  be  too  intense,  the  general  perturbation  too  great,  for 

*  Cases,  Journ.  de  Pharm.  ei  de  CJiimie,  June,  1871. 


COUNTER-IRRITANTS.  771 

erotism  to  be  induced.  There  appear  to  be  the  same  differences  in  the  effects  of  dif- 
ferent doses  of  the  drug  upon  animals.  Fatal  doses  very  generally  do  not  excite 
sexual  desire  ;  but  Schubarth  (quoted  by  Stille')  found  that  small  doses  do  cause 
evident  salaciousness  and  irritation  of  the  genital  organs,  while,  according  to  Huse- 
mann,2  the  peasants  of  Northern  Germany  habitually  give  cantharides  to  cows  when 
backward  in  coming  into  heat  at  the  proper  season. 

According  to  Cautieri,3  toxic  doses  of  cantharides  rapidly  lessen 
blood- pressure  and  the  force  of  the  cardiac  pulsations,  but  markedly 
increase  the  pulse-rate.  Cautieri  found  in  animals  killed  with  cantharides 
marked  hyperaemia  of  the  brain  and  spinal  cord,  and  nephritis  :  Galippe 4 
noted  inflammation  of  the  alimentary  canal,  kidneys,  and  bladder. 

THERAPEUTICS. — Cantharides  is  employed  internally  only  for  the 
purpose  of  influencing  the  genito- urinary  organs.*  When  cantharides 
is  freely  used  externally  as  a  vesicant  there  is  always  some  danger  of  the 
absorption  of  a  sufficient  amount  of  the  active  principle  for  strangury 
to  be  induced.  The  blister  should  therefore  not  be  left  on  longer  than  is 
absolutely  necessary,  and  in  susceptible  persons  care  has  to  be  exercised 
in  its  use  :  whenever  active  irritation  of  the  kidneys  exists,  cantharidal 
blisters  should  not  be  applied,  f 

TOXICOLOGY. — The  minimum  fatal  dose  of  cantharides  is  not  certainly 
determined,  and  probably  varies  very  much.  According  to  Stille, 
twenty-four  grains  of  the  powder,  taken  in  two  doses,  have  caused 
fatal  abortion,  and  an  ounce  of  the  tincture  has  destroyed  life  after  the 
lapse  of  a  fortnight.  After  death,  intense  injection,  swelling,  patches  of 
exudation,  loss  of  epithelium,  and  other  results  of  inflammation  are 
found  along  the  whole  tract  of  the  alimentary  canal  ;  intense  hyperaemia 
of  the  kidneys,  with  contraction  and  congestion  of  the  bladder,  also 
usually  exists.  According  to  the  experiments  of  Aufrecht,5  all  the  forms 
of  nephritis  may  be  produced  by  cantharidin,  but  it  is  probable  that  in 
most  cases  of  poisoning  the  first  change  is  exudation  of  the  white  blood- 
corpuscles,  rapidly  followed  by  a  desquamative  nephritis,  with  profound 
alteration  in  the  glomerules  (see  Ida  Eliaschoff6). 

There  is  no  known  antidote  to  cantharides,  and  the  treatment  of  the 
poisoning  must  be  conducted  upon  general  principles.  The  stomach 
should  be  washed  out  repeatedly  and  freely  by  large  draughts  of  warm 
water,  aided  by  the  stomach-pump  or  tube,  or  by  a  stimulating  emetic  if 
the  stomach-pump  be  not  at  hand.  Large  quantities  of  mucilaginous  or 
albuminous  drinks  should  be  taken  ;  and  all  oily  substances  should  be 
avoided,  as  favoring  the  solution,  and  consequently  the  absorption,  of  the 
poison.  Opium  should  be  freely  exhibited,  especially  by  the  rectum,  to 
allay  pain  and  relieve  the  strangury.  For  the  latter  purpose  warm  sitz- 

*  See  DIURETICS  and  EMMENAGOGUES. 

f  In  1891  Liebreich  advocated  the  use  of  cantharidin  salts  in  lupus,  phthisis,  and 
other  forms  of  tubercular  disease.  His  theory  of  their  action  was,  however,  very  im- 
probable, and  the  method  has  so  entirely  failed  in  practice  that  it  is  not  necessary  here 
to  do  more  than  refer  the  curious  reader  to  the  tenth  edition  of  this  treatise  for  informa- 
tion concerning  it. 


772  LOCAL    REMEDIES. 

baths  or  general  baths  should  be  employed.  In  some  cases  leeches  to 
the  epigastrium  are  advisable.  When  the  suffering  is  very  intense,  the 
cautious  use  of  anaesthetics  is  not  only  justifiable,  but  imperative. 

ADMINISTRATION.-— For  blistering,  the  Cantharides  Cerate  (CERATUM 
CANTHARIDIS,  U.  S. )  is  best  spread  upon  sticking-plaster  in  such  a  way 
as  to  leave  a  margin  about  an  inch  in  width,  which  shall  adhere  to  the 
skin  and  hold  the  plaster  in  its  place.  In  order  for  a  blister  to  "  draw" 
thoroughly,  it  usually  has  to  be  left  on  some  eight  hours  ;  but  in  most 
cases  the  same  result  can  be  achieved  with  less  suffering  by  allowing  the 
blister  to  remain  only  five  or  six  hours,  or  until  decided  redness  and 
slight  vesication  have  been  induced,  and  then  applying  a  flaxseed  poul- 
tice. In  certain  localities  vesication  requires  a  much  longer  application 
than  that  just  spoken  of  ;  thus,  upon  the  shaved  scalp  a  blister  will 
rarely  act  efficiently  in  less  than  twelve  hours,  and  often  not  in  that 
time.  In  maniacs,  in  the  delirious  sick,  in  children,  and  in  other  unruly 
patients  it  is  often  necessary  to  put  on  a  blister  in  such  a  way  that  the 
sick  person  has  no  control  over  it.  For  this  purpose  the  Cantharidal 
Collodion  (CoLLODiuM  CANTHARIDATUM — sixty  per  cent.,  U.  S. )  *  may 
be  used.  It  is  ordinary  collodion  impregnated  with  cantharidin,  and  on 
evaporation  leaves  an  adhesive  blistering  film  :  two  or  three  coats  of  it 
should  be  applied  by  means  of  a  camel' s-hair  brush.  When  there  is 
any  especial  danger  to  be  feared  from  absorption  of  the  active  principle, 
the  use  of  the  poultice,  after  a  brief  application  of  the  blister  as  de- 
scribed above,  should  always  be  practised.  The  tincture  (TiNCTURA 
CANTHARIDIS — ten  per  cent. ,  U.  S. )  is  used  internally  in  doses  of  one  to 
two  drops  (0.06-0.12  C.c. ). 

R  UBEFA  CIENTS. 

SINAPIS  ALBA— WHITE  MUSTARD.     U.  S. 
SINAPIS  NIGRA— BLACK  MUSTARD.     U.  S. 

The  seeds  of  Brassica  alba  and  Brassica  nigra  respectively, — Euro- 
pean crucifers,  cultivated  in  the  temperate  regions  of  the  world.  These 
seeds  are  minute,  globular  bodies,  yellowish  within  :  they  are  to  be  dis- 
tinguished one  from  the  other  by  the  smaller  size,  external  brown  color, 
and  more  fiery  taste  of  the  black  mustard,  and  the  light  yellowish  exte- 
rior of  the  white  mustard. 

Black  Mustard  yields  on  distillation  a  volatile  oil,  which  does  not 
pre-exist  in  the  seeds,  but  is  formed  by  the  decomposition  of  sinigrin  or 
potassium  myronate  in  the  presence  of  emulsin.  OLEUM  SINAPIS  VO- 
LATILE, U.  S.,  is  a  colorless  or  yellowish  fluid,  of  an  intensely  pungent, 
or  corrosive,  odor  and  taste.  A  momentary  contact  with  it  suffices  to 
redden  and  blister  the  skin,  and  mucous  membranes  are  said  to  be  rap- 
idly destroyed  by  its  vapors. 

WJiite  Mustard  contains  sinalbin,  which  in  the  presence  of  water  and 

*  For  a  case  of  poisoning  by  cantharidal  collodion,  see  Phila.  Med.  Times,  iv.  312. 


COUNTER-IRRITANTS.  773 

emulsin  forms  acrinyl  sitlphocyanate,  an  oily,  non- volatile,  very  acrid  sub- 
stance, upon  which  the  activity  of  white  mustard  depends. 

THERAPEUTICS. — Mustard  affords  a  most  excellent  material  for  the 
practice  of  mild  revulsion.  One  advantage  it  possesses  is  the  ease  with 
which  it  can  be  controlled,  all  grades  of  action,  from  the  mildest  impres- 
sion up  to  severe  blistering,  being  at  the  will  of  the  practitioner.  It  should 
be  remembered,  however,  that  the  blister  produced  by  it  discharges  but 
little,  and  is  exceedingly  sore  and  painful,  as  well  as  very  slow  and  diffi- 
cult of  healing  :  so  that,  as  an  epispastic,  mustard  is  in  every  way  infe- 
rior to  cantharides,  and  should  not  be  employed.  The  black  mustard  is 
much  stronger  than  the  white,  and  must  usually  be  diluted  at  least  one- 
half  (by  the  addition  of  flour  or  of  flaxseed  meal).  The  white  variety 
may  sometimes  be  employed  pure,  but  generally  it  also  should  be  reduced 
in  strength. 

In  many  cases  it  is  desirable  to  maintain  for  hours  a  mild,  equable 
counter-irritant  impression,  and  this  may  be  done  by  adding  from  one  to 
three  teaspoonfuls  of  mustard,  more  or  less,  to  a  poultice  of  flaxseed. 
A  mustard  poultice  (half-and-half  black  mustard,  three  parts  to  one  of 
white  mustard  and  flour)  may  generally  be  left  on  from  twenty  minutes 
to  half  an  hour  without  danger  of  blistering.  Weaker  preparations  may 
be  used  longer. 

A  mustard  plaster  may  be  prepared  like  an  ordinary  poultice  ;  but  a  very  con- 
venient method  is  to  take  a  newspaper  folded  to  a  little  larger  than  the  desired  size, 
and  tear  open  the  front  piece  so  that  it  can  be  folded  back  like  a  flap,  leaving  one 
edge  attached  ;  next,  to  spread  upon  the  thick  portion  the  mustard,  leaving  the 
edges  free,  and  then  to  close  the  flap  upon  it  and  fold  the  edges  back  to  the  desired 
shape :  when  done  with,  this  plaster  can  be  thrown  away,  and  no  rags  are  lost. 
The  mustard  draws  well  through  the  single  layer  of  newspaper  covering  it,  but  is, 
we  think,  less  apt  to  leave  troublesome  after-soreness  than  when  employed  in  the 
usual  manner. 

CHARTA  SINAPIS,  U.  S. ,  or  Mustard  Paper,  consists  of  black  mustard 
mixed  with  solution  of  gutta-percha  and  spread  upon  stiff  paper  four 
inches  square.  It  is  not  so  good  as  the  domestic  plaster,  because  not  so 
easily  regulated  as  to  power  and  size. 

CAPSICUM  and  the  stronger  spices  afford  excellent  materials  for  rube- 
faction.  Cayenne  pepper  is  nearly  as  strong  as  mustard,  but  is  much 
less  pleasant  to  handle,  on  account  of  the  readiness  with  which  it  is  dif- 
fused, and  is  much  less  frequently  employed.  Spice-plasters  are  useful 
when  it  is  desired  to  make  a  steady,  continuous  mild  impression,  as  in 
certain  abdominal  complaints. 

Spice-plasters  may  be  made  by  the  apothecary  by  means  of  the  following  recipe. 
Take  of  powdered  ginger,  3  "  ;  powdered  cloves  and  cinnamon,  each,  g  i ;  Cayenne 
pepper,  3  ii ;  tincture  of  ginger,  f  3  ss  ;  honey,  q.  s.  ;  mix  the  powders,  add  the  tinc- 
ture, and  sufficient  honey  to  make  of  proper  consistence  for  a  stiff  cataplasm.  The 


774  LOCAL    REMEDIES. 

domestic  spice-plasters  are  much  more  elegant  and  cleanly  than  those  made  on  the 
above  plan.  They  are  to  be  prepared  as  follows.  Take  equal  parts  of  ground  ginger, 
cloves,  cinnamon,  and  allspice,  and  one-fourth  part  of  Cayenne  pepper,  and  thor- 
oughly mix  them  ;  then  put  the  resulting  dry  powder  into  a  previously  prepared 
flannel  bag  of  the  desired  size,  distribute  the  powder  equably  through  the  latter, 
and  quilt  it  in, — i.e.,  run  lines  of  stitching  across  the  bag,  so  as  to  confine  the  pow- 
der in  little  compartments  :  when  using,  moisten  thoroughly  with  common  whiskey 
or  with  alcohol.  A  plan  which  has  seemed  to  us  still  more  pleasant  is  to  put  two 
ounces  of  unground  ginger,  an  ounce  of  unground  cloves,  cinnamon,  and  chillies, 
or  African  peppers,  in  a  pint  bottle,  and  pour  the  whiskey  upon  them.  After  this 
has  stood  awhile,  the  liquor  is  to  be  put  upon  a  piece  of  flannel  of  the  proper  size, 
and  the  latter  is  to  be  laid  upon  the  part  and  covered  with  a  larger  piece  of  oiled 
silk,  or  else  a  piece  of  spongiopilin  may  be  employed.  If  the  strength  of  the  prep- 
aration is  too  great,  it  can  readily  be  reduced  by  dilution  ;  if  it  is  too  little,  it  can 
as  readily  be  increased  by  adding  more  of  the  spices,  especially  of  the  peppers.  In 
many  cases,  when  the  tenderness  is  very  great,  the  weight  of  the  spice-plaster  is 
objected  to.  Under  these  circumstances  the  substitute  here  proposed  is  especially 
valuable. 

OIL  OF  TURPENTINE  is  a  very  powerful  rubefacient,  capable,  if  ap- 
plied to  the  skin  for  too  long  a  time,  of  destroying  the  epidermis.  It 
produces,  when  properly  used,  simply  an  intense  diffused  redness.  The 
most  frequent  mode  of  application  is  in  the  form  of  stupes,  which  should 
be  made  by  dipping  a  piece  of  flannel,  previously  wrung  out  with  warm 
water,  into  a  cup  of  turpentine  which  has  been  warmed  by  setting  it 
in  hot  water,  and  then  wringing  out  all  excess  of  the  turpentine  and 
applying.  These  stupes  may  be  left  on  from  ten  to  thirty  minutes,  ac- 
cording to  the  severity  of  the  impression  desired  and  the  susceptibility 
of  the  patient's  skin.  On  some  persons  the  least  contact  of  turpentine, 
or  even  of  its  vapors,  produces  a  most  painful  furuncular  eruption. 
Where  this  idiosyncrasy  exists,  of  course  the  remedy  should  never  be 
used.  The  official  liniment  (LINIMENTUM  TEREBINTHIN^E,  U.  S. , 
Kentish  Ointment)  has  been  used  as  a  stimulant  application  to  burns 
and  old  ulcers,  but  has  passed  out  of  vogue. 

AMMONIA  is  a  most  efficient  rubefacient,  which  in  its  general  relations 
has  been  sufficiently  discussed  elsewhere.  When  great  haste  is  required, 
it  may  be  employed  as  an  epispastic  by  applying  a  piece  of  common 
lint  saturated  with  the  stronger  water  of  ammonia,  and  covering  it  with 
some  impervious  coating.  Great  care  must  be  practised  lest  the  am- 
monia act  as  an  escharotic,  since  a  too  prolonged  application  may  pro- 
duce a  deep  slough.  To  raise  a  blister  requires  from  five  to  ten  minutes. 
On  account  of  its  cheapness  and  efficiency,  ammonia  is  very  largely  used 
in  extemporaneous  liniments.  In  prescribing,  it  must  always  be  borne 
in  mind  that  there  are  two  waters  of  ammonia, — AQUA  AMMONITE  FOR- 
TIOR,  U.  S. ,  with  a  specific  gravity  of  o.  90,  containing  twenty-eight  per 
cent,  by  weight  of  the  gas,  and  AQUA  AMMONITE,  U.  S. ,  with  a  specific 
gravity  of  0.960,  containing  ten  per  cent,  by  weight  of  the  gas.  The 
rubefacient  action  of  ammonia  is  less  permanent  than  that  of  turpentine. 


COUNTER-IRRITANTS.  775 

The  liniment  (LINIMENTUM  AMMONITE,  U.  S. )  is  composed  of  three 
hundred  and  fifty  parts  of  ammonia  water,  fifty  parts  of  alcohol,  and. 
six  hundred  parts  of  cotton-seed  oil. 

Burgundy  Pitch  was  formerly  official.  It  is  a  concrete  juice  ob- 
tained by  wounding  the  Abies  excelsa,  or  Norway  spruce, — lofty  forest 
trees  of  Middle  and  Northern  Europe, — melting  the  product  of  the 
exudation  with  hot  water,  and  straining.  It  is  hard,  opaque,  brittle, 
of  a  feeble  terebinthinate  odor  and  taste,  and  contains  resin  and  a  minute 
amount  of  volatile  oil.  It  is  a  mild  rubefacient,  which,  in  the  form  of 
plaster,  may  be  kept  applied  for  a  long  time  in  chronic  bronchitis  and  in 
rheumatic  affections  of  the  trunkal  muscles.  The  plaster  contains  fifteen 
per  cent,  of  wax.  The  Wanning  Plaster  contains  one  part  of  cantharides 
cerate  to  twelve  parts  of  Burgundy  pitch,  and  is  a  very  decided  counter- 
irritant  whose  prolonged  use  will  sometimes  blister. 

CARBONEI  DISULPHIDUM.  U.  S.  Carbon  Disulphide.  —  Carbon  Bi- 
sulphide.— A  clear,  colorless,  highly  refractive,  very  volatile  liquid,  of  a 
strong,  disagreeable  odor  and  a  sharp  aromatic  taste.  It  is  very  much 
used  in  the  arts  as  a  solvent,  and  is  an  active  poison,  half  an  ounce  of  it 
having  produced  death,  preceded  by  coma,  with  collapse  and  abolition 
of  reflexes.  It  has  not  been  used  as  an  internal  remedy,  but  has  been 
employed  as  a  counter-irritant  and  local  anaesthetic  for  the  relief  of  focal, 
facial,  and  other  neuralgias.  A  small  dossil  of  cotton,  saturated  with  the 
drug,  should  be  placed  on  the  part  and  covered  with  wax  paper  ;  or 
better,  a  wide-mouthed  bottle  containing  the  disulphide  and  cotton  may 
be  inverted  upon  the  part  for  a  few  minutes.  Even  the  counter-irritant 
use  of  carbon  disulphide  is  not  to  be  encouraged. 


REFERENCES. 

COUNTER-IRRITANTS.  3.  CAUTIERI S.  Jb.,  clxv.  237. 

1.  PALLE Journ.    de    Pharm.    et   de       4.  GALIPPE G.  H.  M.  C..  1874,  439. 

Chim.,  June,  1871.  5.  AUFRECHT    .   .   .   .  C.  M.  W.,  1882,  xx.  850 

2.  HUSEMANN  ....  Handb.    der    Toxicologie,       6.  EUASCHOFF    .   .    .  V.  A.  P.  A.,  xciv.  323. 

1862,  264.  7.  THOMPSON   ....  Brit.  Med.  Jour.,  1887. 


FAMILY   X.— ESCHAROTICS. 


ESCHAROTICS  are  drugs  which  are  used  to  destroy  diseased  or  sound 
tissue.  Many  of  them  exert  a  purely  chemical  influence,  while  others 
seem  to  destroy  life  by  directly  affecting  the  vitality  of  the  part,  and 
are  said  to  act  dynamically.  Those  which  act  chemically  do  so  in  sev- 
eral ways  :  some,  like  bromine,  probably  produce  an  intense  corrosive 
oxidation,  while  others,  like  sulphuric  acid,  abstract  the  water. 

Escharotics  are  used  for  various  purposes.  Formerly  they  were 
employed  to  open  abscesses  ;  but  in  the  very  few  cases  in  which  the 
knife  is  not  allowable,  aspiration  usually  affords  a  superior  and  safer 
method.  They  are  constantly  applied  to  destroy  unsound,  harmful 
tissues  and  growths.  Thus,  they  are  used  to  remove  the  specific  tissue 
of  a  chancre,  or  to  kill  a  malignant  or  semi-malignant  tumor.  Another 
purpose  which  they  fulfil  is  the  destruction  of  poisoned  wounds.  In 
these  cases  they  may  in  some  instances  destroy  the  poison  itself,  but 
at  other  times  they  simply  prevent  the  absorption  of  the  toxic  agent 
by  putting  an  end  to  the  life-actions  of  the  tissue  containing  it.  It  is 
hardly  necessary  to  mention  all  the  various  cases  in  which  caustics  are 
employed  to  overcome  the  effects  of  poisoned  wounds.  Hydrophobia  is 
a  perfectly  uncontrollable  disease  ;  but  the  thorough  destruction  of  the 
wounded  tissue  at  any  time  before  the  manifestation  of  the  symptoms 
will  probably  prevent  its  occurrence,  as  it  certainly  will  if  performed 
early.  In  malignant  pustule,  life  depends  upon  the  free  early  use  of 
escharotics.  Escharotics  are  employed  to  produce  ulcerations  which 
shall  be  the  bases  of  issues ;  also,  by  destroying  the  exuberant  granula- 
tions or  the  indolent  surfaces  of  ulcers,  to  remove  at  the  same  time  dis- 
eased tissue,  afford  protection  to  the  parts  below  by  forming  an  imper- 
meable surface,  and  exert  such  alterative  action  upon  the  part  as  shall 
modify  for  good  the  life-processes. 

It  is  evident  that  the  choice  of  the  caustic  should  depend  upon  the 
object  to  be  attained.  When  large  tumors  are  to  be  killed,  or  when  it 
is  all-important  completely  to  destroy  a  poisoned  wound,  a  powerful 
deep-reaching  escharotic  must  be  employed  ;  but  when  the  surface  of  an 
ulcer  is  to  be  filmed  over,  a  caustic  which  acts  superficially  and  forms 
a  dense  albuminous  coating,  as  does  silver  nitrate,  is  to  be  chosen. 

An  observation  of  N.  A.  Randolph  and  S.  G.  Dixon '  indicates  that 
the  pain  produced  by  a  caustic  may  be  almost  nullified  by  the  use  of 
776 


ESCHAROTICS.  777 

cocaine.  They  find  that  the  saturated  solution  of  cocaine  in  nitric  acid 
acts  as  powerfully  as  nitric  acid,  although  much  more  slowly,  and  that  the 
only  sensation  experienced  during  the  production  of  even  a  deep  eschar 
is  a  slight  prickling. 

All  of  the  more  powerful  of  the  escharotics,  when  taken  internally  in 
sufficient  amount,  act  as  violent  corrosive  poisons,  producing  agonizing 
pain  in  the  oesophagus  and  hypogastrium,  violent  bloody  vomiting,  often 
purging  of  similar  character,  and  finally  collapse,  deepening  into  death, 
which  is  sometimes  preceded  by  convulsions.  When  the  dose  is  not  so 
large,  the  patient  may  rally  from  the  immediate  effects  of  the  poison,  to 
succumb  finally  to  the  local  lesions  produced,  or  to  struggle  through  a 
protracted  convalescence  to  health,  perhaps  only  to  die  years  afterwards 
from  organic  stricture,  caused  by  the  ulcerations  of  the  oesophagus  or 
other  of  the  digestive  tubes.  The  first  indication  in  poisoning  by  one  of 
these  substances  is  to  neutralize  or  chemically  antidote  the  poison  :  with 
the  alkalies,  dilute  acid,  generally  convenient  in  the  form  of  vinegar; 
with  the  acids,  alkalies,  usually  at  hand  in  the  shape  of  whitewash  or  of 
soap  ;  with  other  poisons,  specific  antidotes.  Opium  should  always  be 
freely  given,  and  the  symptoms  during  and  after  the  first  poisoning  be 
treated  as  they  arise. 

POTASSII  HYDROXIDUM.  U.  S. — Caustic  Potash  occurs  in  grayish, 
semi-translucent  sticks,  about  three  inches  long  and  as  thick  as  a 
large  goose-quill,  very  deliquescent,  and  extremely  soluble  in  both  water 
and  alcohol.  When  it  is  placed  upon  the  skin  it  soon  melts,  and,  as  it 
does  so,  gives  rise  to  a  pain  which  increases  until  it  becomes  very  intense, 
and  continues  until  the  power  of  the  alkali  is  so  diminished  that  it  can 
no  longer  reach  through  the  tissue  it  has  killed  to  the  sound  flesh  below. 
Under  the  action  of  the  escharotic  the  skin  becomes  of  a  dirty  ashen- 
gray,  and  finally  a  slough  is  formed,  with  inflammation  of  the  surround- 
ing parts,  and  ulceration  and  detachment  of  the  dead  tissue  in  from  six 
to  ten  days.  The  potash  appears  to  act  chiefly  by  abstracting  the  water, 
and,  to  some  extent,  by  combining  with  the  fatty  and  other  portions  of 
the  tissues.  Its  slough  being  perfectly  permeable,  and  its  power  being 
but  slowly  expended  by  its  own  action,  potash  is  one  of  the  most  thor- 
ough of  the  escharotics  :  it  is,  therefore,  to  be  preferred  when  a  very 
deep  and  decided  influence  is  required,  as  after  the  bite  of  -\  rabid  dog. 
It  is  somewhat  uncontrollable  in  its  action,  and  requires  care  in  its  use. 
The  best  method  of  application  is  as  follows.  Take  a  piece  of  thick 
adhesive  plaster,  and  cut  a  hole  in  it  of  such  size  that,  when  the  piece  is 
warmed  and  properly  placed  upon  the  skin,  the  part  to  be  acted  upon 
will  be  exposed  while  all  around  it  will  be  protected.  Then  apply  the 
plaster,  and  grease  the  outer  surface  of  it,  without  allowing  any  of  the 
oil  to  come  in  contact  with  the  exposed  central  skin.  Then  lay  the 
caustic  potash  upon  the  latter,  and,  when  the  action  is  believed  to  have 
extended  deep  enough,  .wash  the  part  with  dilute  vinegar. 


778  LOCAL    REMEDIES. 

POTASSA  CUM  CALCE,  1890. —  Vienna  Paste,  a  grayish- white  powder, 
composed  of  equal  amounts  of  caustic  potash  and  caustic — /.  e. ,  unslaked 
— lime.  It  is  not  so  active  as  caustic  potash,  but  is  less  apt  to  spread 
and  diffuse  itself.  It  is  to  be  mixed  with  sufficient  alcohol  to  form  a 
paste,  and  then  applied  like  caustic  potash. 

Piedagnel 2  affirms  that  this  caustic  may  be  rendered  nearly  or  entirely  painless 
by  mixing  one  part  of  morphine  hydrochlorate  with  three  parts  of  the  powder,  and 
then  by  the  addition  of  chloroform  forming  a  paste  that  may  be  spread  upon  lead 
plaster  and  so  applied.  In  five  minutes  the  skin  under  the  application  becomes  of 
a  dead-white  color,  and  at  the  end  of  fifteen  minutes  is  brown  and  carbonized.  If 
the  application  be  persisted  in,  the  thickness  of  the  eschar  will  become  finally 
about  equal  to  that  of  the  layer  of  the  paste  employed.  Cocaine  would  probably  be 
more  efficient  in  preventing  pain  than  the  morphine. 

ARSENI  TRIOXIDUM.  U.  S. — As  a  caustic,  arsenic  is  energetic  and 
powerful,  but  somewhat  slow,  and  causes  intense  pain,  with  violent  inflam- 
mation of  the  neighboring  parts.  It  is  stated  to  affect  more  rapidly  mor- 
bid than  normal  structures,  and  is  especially  used  for  the  destruction  of 
malignant  growths.  It  appears  to  act  chiefly  upon  the  vitality  of  the 
part,  acting,  when  sufficiently  diluted,  as  a  powerful  irritant,  and  when 
in  a  concentrated  form  producing  an  irritation  so  intense  that  life  cannot 
endure  it.  Hence,  probably,  the  reason  of  its  affecting  more  rapidly 
morbid  growths,  which  have  a  lower  vitality  than  sound  tissues. 

The  great  objection  to  the  employment  of  arsenic  is  the  possibility 
of  its  absorption  in  sufficient  amount  to  cause  constitutional  symptoms  : 
even  death  has  resulted  from  its  external  use.  Since  absorption  takes 
place  much  more  rapidly  in  a  healthy  than  in  an  intensely  inflamed  or  a 
dead  tissue,  whenever  arsenic  is  employed  as  a  caustic  it  should  be  used 
so  freely  as  to  kill  the  tissues  rapidly,  and  under  no  circumstances 
should  it  be  applied  to  a  fresh  wound.  Used  in  any  way,  arsenic  is  a 
hazardous  caustic,  and  it  ought  to  be  employed  only  with  the  knowledge 
and  distinct  remembrance  of  this  fact.  Cancer,  and  perhaps  some  forms 
of  semi-malignant  ulceration,  such  as  lupus,  appear  to  be  the  only  dis- 
eases which  justify  its  use. 

There  is  no  reason  for  believing  that  any  of  the  almost  innumerable 
substances  which  have  been  proposed  as  a  basis  for  arsenous  pastes  pos- 
sess peculiar  advantages  :  the  only  needful  direction  is  to  mix  the  caustic 
with  from  eight  to  ten  times  its  bulk  of  inert  material  of  such  a  nature  as 
to  make  either  an  ointment  or  a  paste,  and  to  allow  this  to  remain  on 
the  part  for  from  eighteen  to  twenty-four  hours. 

ZINCI  CHLORIDUM.  U.  S. — Zinc  Chloride  occurs  in  broken  fragments 
of  a  grayish-white  color,  translucent  and  waxy  in  appearance,  of  an  acrid 
corrosive,  or,  when  diluted,  acrid  astringent,  metallic  taste.  It  is  ex- 
tremely deliquescent,  fusible,  volatilizable  at  a  high  temperature,  and 
very  soluble  in  both  water  and  alcohol.  Zinc  chloride  is  a  very  powerful 


ESCHAROTICS.  779 

caustic,  producing,  when  applied  in  a  concentrated  form,  intense  pain 
lasting  from  six  to  eight  hours,  and  a  whitish  eschar,  which  usually  sep- 
arates in  from  six  to  twelve  days.  Its  penetrating  powers  are  a  little 
less,  and  its  action  more  readily  controlled,  than  is  that  of  potash  ;  its 
absorption  does  not  endanger  life,  as  is  the  case  with  arsenous  acid  ;  and 
it  leaves  a  slough  which  is  free  from  odor. 

Canquoiri  s  Paste  is  made  by  mixing  zinc  chloride  with  flour  and 
water.  The  strength  varies  according  to  the  purpose,  the  weakest  paste 
containing  only  one  part  of  the  caustic  in  six  parts  ;  the  strongest,  one 
part  in  three.  When  used,  ten  or  fifteen  drops  of  water  are  added  to 
the  paste,  which  is  applied  in  layers,  successive  applications  being  re- 
quired when  a  large  tumor  is  to  be  destroyed.  Anhydrous  calcium  sul- 
phate has  been  especially  commended  by  A.  Ure,  as  forming  a  drier  paste 
with  the  escharotic  and  limiting  its  action  more  definitely  to  the  site  of 
application  than  any  other  substance.  Concentrated  alcoholic  or  watery 
solutions  of  zinc  chloride  are  often  used  as  caustics  in  cases  of  chancres 
and  other  small  specific  ttlcers,  and  are  reputed  to  be  efficient.  They 
should  be  applied  by  means  of  little  pledgets  of  lint.  As  the  action  of 
the  chloride  upon  the  skin  is  slow  and  very  painful,  whenever  the  cuticle 
over  the  part  to  be  destroyed  is  sound  it  should  be  removed  by  means  of 
blisters.  By  some  surgeons  the  escharotic  is  introduced  directly  into  the 
tumor  to  be  destroyed.  The  official  solution  (LIQUOR  ZINCI  CHLORIDI, 
U.  S. )  has  been  used  as  a  disinfectant,  but  is  of  very  little  value. 

HYDRARGYRI  CHLORIDUM  CORROSIVUM.  U.  S. — Corrosive  Sublimate 
is  an  escharotic  of  moderate  power,  which  shares  the  dangers  of  arsenic, 
since  death  has  followed  its  external  use.  In  saturated  solution  it  is  much 
used  as  a  caustic  in  chancres,  but  is  scarcely  equal  to  the  solution  of  mer- 
curic nitrate.  In  these  cases  it  should  be  applied  by  means  of  a  camel' s- 
hair  brush.  The  late  George  B.  Wood  recommended  very  highly  that  in 
onychia  maligna  a  powder  composed  of  equal  parts  of  corrosive  subli- 
mate and  zinc  sulphate  intimately  mixed  should  be  sprinkled  thickly  over 
the  diseased  surface,  and  a  pledget  of  lint  thoroughly  wet  with  laudanum 
laid  thereon.  There  is  severe  pain  for  half  an  hour  to  an  hour  ;  but  the 
dressings  are  not  to  be  removed  until  eight  or  ten  hours  have  elapsed. 
When  the  slough  which  is  thus  formed  separates,  a  healthy  granulating 
surface  is  left. 

LIQUOR  HYDRARGYRI  NITRATIS.  U.  S. — Solution  of  Mercuric  Nitrate 
is  a  nearly  colorless,  highly  corrosive,  acid  liquid,  having  a  specific 
gravity  of  2.086,  and  made  by  dissolving  mercury,  or  its  red  oxide,  in 
a  large  excess  of  nitric  acid.  Its  application  to  a  space  not  bigger 
than  a  half-crown  has  produced  very  serious  poisoning.*  It  is  rarely 
used,  except  for  the  purpose  of  destroying  specific  or  cancerous  ulcers. 

*  Case,  I^ancet,  January  3,  1874. 


780  LOCAL    REMEDIES. 

It  is  especially  useful  in  chancres,  to  which  it  should  be  applied  with  a 
glass  rod.  In  obstinate  acne,  an  indolent  tubercle  may  be  destroyed  by  a 
minute  drop  without  producing  a  scar.  It  has  been  largely  employed  by 
gynaecologists  in  ulcerations  of  the  cervix  uteri.  Its  action  is  very  prompt 
and  is  moderately  deep;  the  pain  is  severe,  but  transient. 

ACIDUM  NITRICUM.  U.  S. — Nitric  Acid  is  a  powerful  caustic,  which 
is  never  employed  to  destroy  large  tumors,  but  is  a  favorite  application  to 
chancres,  to  syphilitic,  phagedenic,  and  other  unhealthy  ulcers,  and  to 
condylomata  and  other  small  dermal  growths.  A  drop  or  two  may  be 
applied  by  means  of  a  glass  rod  or  a  wood  splinter,  and  when  the  action 
has  gone  far  enough,  neutralized  with  soapsuds. 

CHROMII  TRIOXIDUM.  U.  S.  —  Chromium  trioxide,  commonly 
known  as  Chromic  Acid,  occurs  in  anhydrous  acicular  crystals,  of  a  deep 
red  color,  and  an  acid,  metallic,  corrosive  taste.  They  are  very  deli- 
quescent, melting  down,  when  exposed  to  the  air,  into  a  deep  red  solution. 
Chromic  acid  is  a  very  active  oxidizer,  and  when  mixed  with  organic 
matter  rapidly  alters  it,  and  if  in  slight  excess  will  dissolve  almost  any 
form  of  tissue.  It  is  used  to  destroy  condylomata  and  other  dermal 
growths,  and  is  best  applied  by  means  of  a  glass  rod,  the  liquid  formed 
by  the  spontaneous  deliquescence  of  the  crystals  being  used.  Chromic 
acid  is  sometimes  prescribed,  dissolved  in  or  made  into  a  paste  with  glyc- 
erin, but  it  is  stated  that  in  mixing  the  two  great  care  must  be  taken  to 
add  the  liquid  slowly  drop  by  drop,  as  otherwise  there  is  danger  of  an 
explosion.  In  the  German  army,  painting  the  soles  of  the  feet  and  the 
skin  between  the  toes  with  a  five  per  cent,  solution  of  chromic  acid  is 
said  to  have  had  a  very  great  influence  in  increasing  the  marching  powers 
of  the  troops,  by  arresting  excessive  sweating  and  hardening  the  skin. 
Chromic  acid  is  a  violent  corrosive  poison,  a  single  drop  of  the  saturated 
solution  having  caused  very  severe  symptoms.*  The  nature  of  the  poison 
may  often  be  recognized  by  the  reddish-brown,  or  more  rarely  greenish, 
discoloration  of  the  skin  of  the  lips  and  of  the  mucous  membrane  of  the 
mouth  and  gullet,  but  this  discoloration  may  be  absent.  In  a  number  of 
cases  death  has  resulted  from  the  too  free  external  use  of  the  acid,  f 

ACIDUM  TRICHLORACETICUM.  U.S. —  Trichloracetic  Acid  occurs  in 
deliquescent  crystals.  It  has  been  used  to  a  considerable  extent  for  the 
destruction  of  papilloma  and  other  growths  ;  a  single  crystal  placed  on  a 
growth  produces  immediately  a  white,  dry,  adherent  mass,  which  falls 
off  in  a  few  days.  The  pain  is  said  to  be  not  at  all  severe,  and  may  be 
entirely  prevented  by  the  use  of  cocaine. 

*  Case,  Brit.  Med.  Journ.,  1889,  i. 

t  For  experiments  as  to  its  effects  on  animals,  see  A.  E.  P.  P.,  vi. ;  also  Strieker's 
Jahrb.,  1877,  139.  For  cases  of  poisoning,  see  Ibid.;  S.  J.,  1884,  cci.  129;  U.  M.  M.,  ii.; 
M.  M.  W.,  1903,  i.  691 ;  D.  A.  K.  U.,  Ixxv. 


ESCHAROTICS.  781 

BROMUM.  U.  S. — Bromine  is  a  dark  red  liquid  which  has  a  very  power- 
ful, disagreeable,  chlorine-like  odor,  and  at  ordinary  temperatures  emits 
exceedingly  acrid,  pungent  fumes.  It  is  sparingly  soluble  in  water, 
more  soluble  in  alcohol,  and  still  more  so  in  ether.  When  brought  into 
contact  with  organic  matter,  it  oxidizes  and  completely  destroys  it  with 
great  rapidity.  On  account  of  this  property  and  of  its  liquid  form, 
bromine  is  one  of  the  most  severe,  thorough,  and  rapid  of  all  the  caus- 
tics. It  has  not  been  much  employed  to  destroy  morbid  growths,  but 
has  been  found  very  efficient  in  hospital  gangrene.  After  most  of  the 
slough  has  been  cut  away,  the  caustic  should  be  applied  pretty  freely 
to  the  living  tissue  by  means  of  a  glass  rod.  When  taken  internally, 
bromine  acts  as  a  very  powerful  corrosive  poison.* 

Zinc  Sulphate,  Copper  Sulphate,  and  Burnt  Alum  are  feeble  escha- 
rotics,  never  used  except  to  destroy  exuberant  granulations  in  ulcer. 

PYROGALLOL.  U.  S. — Pyrogallic  Acid. — This  triatomic  phenol  may 
be  prepared  synthethically,  but  is  usually  obtained,  in  accordance  with 
the  directions  in  the  U.  S.  Pharmacopoeia,  as  the  result  of  the  igneous 
decomposition  of  gallic  acid.  In  concentrated  form  it  is  a  powerful  caus- 
tic, and  as  such,  and  also  in  the  form  of  dilute  ointment  or  solution,  five 
to  forty  grains  to  the  ounce,  has  been  considerably  used  in  the  treatment 
of  lupus,  psoriasis,  and  allied  affections  of  the  skin.  It  is  a  violent 
poison,  and  in  various  cases  death  has  followed  its  too  free  external  use. 
Half  an  ounce  of  it,  taken  internally,  has  produced  death  in  four  days. 
The  symptoms  which  follow  its  external  use  have  been  malaise,  vomiting, 
diarrhoea,  headache,  pallid  and  cyanosed  lips,  collapse,  a  peculiar 
greenish  hue  of  the  skin,  rapid  pulse  and  respiration,  albuminous  urine, 
becoming  dark  brown  or  black  from  the  presence  of  methaemoglobin, 
icterus,  insomnia,  restlessness  with  diminished  reflexes,  and  death  pre- 
ceded by  delirium,  convulsions,  and  coma.  In  pregnant  women  abortion 
without  death  of  the  mother  has  occurred  as  the  result  of  the  external 
use  of  the  ten  per  cent,  ointment  of  the  pyrogallol,  in  psoriasis  (  Busch1). 
When  the  poison  has  been  due  to  the  internal  use,  violent  burning  pains, 
black  vomit,  and  other  evidences  of  its  irritation  to  the  gastro-intestinal 
tract  are  usually  present.  As  noted  by  Personne,4  these  symptoms  re- 
semble those  of  phosphorus-poisoning,  and  wide-spread  fatty  degenera- 
tion and  other  post-mortem  lesions  similar  to  those  caused  by  phos- 
phorus are  found  after  death. 

REFERENCES. 

2.  PIKDAGNEL  ....  Journ.    dc    Pharm.    et   de 
ESCHAROTICS.  Chim.,  3  s.,  xxxiii. 

i    RANDOLPH   and    DIXON  .  M.    News,   Jan.   4,       3.   BUSCH W.  K.  W.,  1901. 

j885.  4-  PKRSONNK    .   .   .   .  C.  R.  A.  S..  1869. 


*  For  cases,  see  Schmidts  Jahrb.,  ccxxi. ;  also  Vierteljahr.  f.  Getichtl.  Med.,  1889. 


FAMILY   XL— DEMULCENTS. 


THESE  are  bland  substances,  which  form  more  or  less  gummy  or 
mucilaginous  solutions  in  water,  capable  of  exerting  a  calming  or  sooth- 
ing influence  upon  inflamed  surfaces.  Their  action  is  probably  purely 
mechanical,  their  adhesiveness  causing  the  water  they  are  in  to  remain 
long  upon  the  part ;  they  are,  as  it  were,  vehicles  for  water,  the  de- 
mulcent par  excellence.  It  has  been  affirmed  not  only  that  demulcents 
soothe  surfaces  to  which  they  are  immediately  applied,  but  also  that  taken 
internally  they  relieve  irritation  in  distant  organs.  There  is,  however,  no 
reason  for  supposing  that  such  of  them  as  escape  digestion  are  absorbed 
or  yield  to  absorption  any  principles  in  sufficient  quantity  to  exert  an  in- 
fluence upon  the  general  system.  The  relief  which  undoubtedly  follows 
their  use  in  certain  affections  of  parts  which  they  can  reach  only  through 
the  circulation  is  probably  due  to  the  large  quantities  of  water  with 
which  they  are  administered,  lessening  the  concentration,  and  hence  the 
acridity,  of  the  urine  and  other  secretions. 

Clinically,  demulcents  are  useful  as  local  applications  in  all  forms  of 
acutely  inflamed  surfaces,  and  they  are  taken  internally  in  acute  inflam- 
matory conditions  of  the  alimentary  canal.  In  slight  bronchial  irritation 
they  are  often  of  service,  especially  when  allowed  to  dissolve  slowly  in 
the  mouth  :  used  in  this  manner,  they  not  only  exert  an  influence  upon 
the  mucous  membrane  of  the  mouth,  but  very  probably  find  their  way 
also  into  the  respiratory  passages. 

ACACIA— GUM    ARABIC.     U.S. 

A  gummy  exudation  from  Acacia  Senegal,  a  small  tree  growing  in 
Northern  Africa,  Senegambia,  Guinea,  etc. ,  the  Cape  Colony,  and  Aus- 
tralia. Gum  arabic  occurs  in  roundish  or  irregular  pieces,  more  or  less 
transparent,  hard,  brittle,  varying  in  color  from  white  or  yellowish  white 
to  red,  or  even  deep  orange  brown.  It  consists  of  a  peculiar,  feebly  acid, 
amorphous  principle,  Arabin,  united  with  about  three  per  cent,  of  lime, 
potash,  and  magnesia.  In  the  plant,  arabin,  like  other  gums,  appears 
to  be  formed  by  a  retrograde  metamorphosis  of  cellulose.  On  account  of 
its  solubility  in  water  and  pleasant  taste,  gum  arabic  is  often  used  as  a 
demulcent  in  irritation  of  the  fauces  and  in  angina.  It  is  sometimes  em- 
ployed as  an  addition  to  drinking-water  in  fevers,  and  is  believed  to  have 
slight  nutritious  properties.  Its  chief  use,  however,  is  in  Pharmacy,  in 
the  making  of  emulsions,  pills,  etc.  The  mucilage  (MuciLAGO 
U.  S. )  is  used  in  various  doses  as  a  vehicle. 
782 


DEMULCENTS.  783 

TRAGACANTHA.  U.  S. —  Tragacanth  is  the  concrete  juice  of  Astraga- 
lus gummifer,  and  of  other  species  of  Astragalus,  a  small  shrub  of  Asia 
Minor.  Tragacanth  occurs  in  large,  whitish,  horny,  waved  flakes,  or 
sometimes  in  filamentous  pieces.  It  is  odorless  and  nearly  tasteless.  In- 
troduced into  water  it  does  not  dissolve,  but  swells  up  into  a  soft  paste. 
One  hundred  parts  of  it  contain,  according  to  Guerin,  53.3  parts  of  ara- 
bin,  33.  i  parts  of  bassorin,  and  2. 5  parts  of  inorganic  ash.  Bassorin 
is  a  gummy  principle,  at  once  distinguished  from  arabin  by  its  not  dis- 
solving in  water,  but  simply  swelling  up  into  a  pasty  mass.  Tragacanth 
is  used  only  in  the  manufacture  of  troches  and  in  suspending  heavy  pow- 
ders, for  which  purpose  the  difficulty  of  its  solution  and  the  extreme 
viscidity  of  its  mucilage  especially  fit  it.  Its  mucilage  (MuciLAGO 
TRAGACANTH^E,  U.  S. )  is  used  in  varying  dose  as  a  vehicle. 

ULMUS.  U.  S.  — Slippery  Elm  is  the  inner  bark  of  Ulmus  f  ulva,  a  large 
indigenous  tree.  The  bark  is  of  a  yellowish-white  or  tan  color,  fibrous, 
yet  when  dry  somewhat  brittle,  and  occurs  in  long,  flat  strips  or  pieces 
one  or  two  lines  thick.  It  is  pleasantly  mucilaginous  when  chewed.  It 
contains  a  large  quantity  of  a  peculiar  mucilage,  which  it  yields  freely  to 
water.  Its  infusion  is  sometimes  taken  in  large  quantities  in  inflamma- 
tions of  the  intestines,  as  a  demulcent  laxative  ;  but  its  chief  use  is  as  an 
external  application.  When  ground  into  powder,  slippery  elm  makes  an 
excellent  soothing  poultice.  The  mucilage  (MUCILAGO  ULMI,  U.  S. )  is 
used  in  varying  dose  as  a  vehicle. 

CHONDRUS.  U.  S. — Irish  Moss,  or  Carrageen. — The  fronds  of  Chon- 
drus  crispus,  and  of  Gigartina  mamillosa,  sea-weed  growing  on  the  coast 
of  Ireland,  and  also  on  the  northern  coast  of  the  United  States,  where 
it  is  now  gathered  in  large  quantities.  The  fronds  are  purplish  red, — 
but,  as  kept  in  the  shops,  bleached  by  washing  in  fresh  water,  whitish 
and  translucent, — cartilaginous,  slender,  much  branched,  swelling  up 
but  not  dissolving  in  water,  and  having  a  slightly  saline  taste.  Their 
virtue  depends  chiefly  upon  a  starch-  or  gum-like  principle,  Carrageenin, 
which  is  distinguished  from  starch  by  not  turning  blue  with  iodine,  and 
from  gum  by  not  precipitating  from  its  watery  solution  on  the  addition 
of  alcohol.  Chondrus  also  contains  a  notable  proportion  of  a  vegetable 
albumin. 

Carrageen,  being  demulcent  and  nutritious,  is  employed  as  an  article 
of  diet  in  those  cases  requiring  food  of  such  character,  and  may  be 
used  instead  of  arrow-root.  It  is  to  be  prepared  by  first  soaking  for  ten 
minutes  in  cold  water,  and  then  boiling  from  half  an  ounce  to  an  ounce 
of  it  (according  to  the  desired  consistency)  in  a  pint  and  a  half  of  water 
down  to  a  pint,  sweetening  and  flavoring  to  taste.  Milk  may  be  substi- 
tuted for  water. 


784  LOCAL    REMEDIES. 

GLYCYRRHIZA.  U.  S. — Licorice  Root  is  the  root  of  Glycyrrhiza 
glabra  and  glandulifera,  native  herbs  of  Southern  Europe.  It  occurs  in 
long,  cylindrical  pieces,  from  a  few  lines  to  more  than  an  inch  in  diam- 
eter, brownish  externally  and  yellowish  within.  Its  fracture  is  fibrous, 
its  taste  sweet  and  mucilaginous,  its  odor  none.  Its  active  principle  is 
Glycyrrhizin.  This  is  a  sweet,  neutral  substance,  differing  from  the 
sugars  in  not  being  converted  by  nitric  acid  into  oxalic  acid,  and  by  its 
inability  to  undergo  the  vinous  fermentation.  Licorice  root  is  very 
largely  used  as  a  demulcent  in  pectoral  complaints,  and,  on  account  of 
its  pleasant  taste,  as  a  means  of  disguising  or  of  flavoring  medicines. 
In  the  form  of  glycyrrhizin  it  is  said  to  conceal  almost  entirely  the  bitter 
taste  of  quinine  and  similar  substances.  It  is  used  almost  exclusively  in 
the  form  of  the  extract  (ExTRACTUM  GLYCYRRHIZA,  U.  S. ),  known  as 
Licorice.  The  MISTURA  GLYCYRRHIZ^E  COMPOSITA,  U.  S. ,  or  Brown 
Mixture,  contains  paregoric,  antimonial  wine,  and  sweet  spirit  of  nitre, 
and  is  much  used  as  a  domestic  remedy  in  colds  and  the  early  stages  of 
mild  bronchitis.  The  dose  for  an  adult  is  half  a  fluidounce  to  a  fluidounce 
(15-30  C.c. )  every  three  hours  ;  for  a  child  three  years  old,  a  teaspoon- 
ful  (3.7  C.c. ).  The  pure  extract  (EXTRACTUM  GLYCYRRHIZA  PURUM, 
U.  S. )  and  the  fluid  extract  (FLUIDEXTRACTUM  GLYCYRRHIZA,  U.  S.) 
are  excellent  preparations.  GLYCYRRHIZINUM  AMMONIATUM,  U.  S.,  is 
an  elegant  demulcent  preparation  which,  however,  is  incompatible  with 
acid  or  alkaline  solutions  :  its  dose  is  from  five  to  ten  grains  (0.3-0.6 
Gm).  The  compound  licorice  powder  (PULVIS  GLYCYRRHIZA  COM- 
POSITUS,  U.  S. )  contains  senna  and  washed  sulphur.  It  is  an  elegant 
laxative,  acting  usually  mildly  and  without  the  production  of  pain,  in 
doses  of  one  to  two  teaspoonfuls  (4-8  Gm. ).  ELIXIR  ADJUVANS,  U.  S. — 
Adjuvant  Elixir  contains  twelve  parts  of  fluid  extract  of  licorice  to  eighty- 
eight  of  Elixir  Aromaticum.  It  affords  an  excellent  aromatic  and 
slightly  demulcent  vehicle  for  extemporaneous  prescriptions. 

LINUM,  U.  S. ,  or  Flax-seed,  is  the  seed  of  Linum  usitatissimum,  or 
common  flax,  and  contains  large  quantities  of  mucilage  and  of  oil ;  its 
infusion,  Flax-seed  tea,  is  much  used  internally.  It  is  often  made  with 
boiling  water  ;  but  the  application  of  too  much  heat  causes  the  extraction 
of  the  oil,  and  renders  the  preparation  less  palatable.  The  addition  of 
lemon  and  sugar  makes  it  more  palatable.  It  may  be  drunk  ad  libitum 
in  pectoral  catarrhs,  in  enteritis  and  dysentery,  and  in  irritation  of  the 
kidneys  or  the  urinary  passages. 

AMYLUM.  U.  S.  Starch. — Obtained  from  Indian  corn,  a  white, 
inodorous,  tasteless  powder,  composed  of  microscopic  granules,  is  phys- 
iologically inert  except  as  a  food.  It  is  often  used  as  a  dusting  powder  in 
irritant  conditions  of  the  skin  ;  as  a  soothing  demulcent  in  the  preparation 
of  opiates  and  other  rectal  injections,  and  pharmaceutically  for  the  purpose 
of  thickening  or  gelatinizing  ointments,  and  the  making  of  paste  for  use 


DEMULCENTS.  785 

in  skin  diseases.  GLYCERITUM  AMYLI,  U.  S.  —  Glycerite  of  starch  is  a 
translucent  jelly,  containing  ten  per  cent,  of  starch,  eighty  per  cent,  of 
glycerin,  ten  per  cent,  of  water,  affording  a  useful  vehicle. 

MEDULLA  SASSAFRAS,  or  Sassafras  Pith,  yields  a  delicate  mucilage 
much  used  in  eye  diseases  (MUCILAGO  SASSAFRAS  MEDULLA,  U.  S). 

ALTHAEA.  U.  S. — The  roots  of  Althaea  officinalis  yield  a  bland  muci- 
lage ;  their  decoction  is  sometimes  given  in  gastric  irritation,  and  their 
syrup  SYRUPUS  AL.THJEJE,  U.  S.  1890)  is  used  as  a  vehicle. 

CETRARIA. — Iceland  Moss  is  the  fronds  of  a  lichen,  Cetraria  islandica,  growing 
on  rocks  in  Iceland  and  in  most  of  the  northern  portions  of  the  world.  It  is  said 
to  be  abundant  in  the  mountains  of  New  England.  The  foliaceous,  dry,  shining, 
lobed,  and  laciniated  fronds  are  about  four  inches  long,  of  various  intermixed 
colors,  gray,  brown,  and  red,  and  of  a  mucilaginous,  bitter  taste.  Iceland  moss 
contains  a  peculiar  lichen  starch  and  a  bitter  principle.  It  yields  to  cold  water  its 
bitterness  ;  to  boiling  water  all  of  its  virtues.  Cetrarin,  or  Cetraric  Acid,  is  the 
bitter  principle,  which  may  be  obtained  as  a  snow-white  mass  of  interlaced  acicu- 
lar  crystals.  It  unites  with  alkalies  to  form  salts.  With  it  in  the  lichen  is  asso- 
ciated in  small  quantities  lichenstearic  acid.  Robert  has  found  that  cetrarin  has  no 
effect  upon  the  arterial  pressure  ;  also  that  in  toxic  dose  it  produces  violent  con- 
vulsions in  the  cat  and  in  the  dog,  whilst  in  small  dose  it  distinctly  increases  the 
activity  of  the  motor  area  of  the  brain  and  spinal  cord.  Robert '  also  asserts  that 
in  healthy  men  cetrarin  increases  the  number  of  the  red  and,  in  a  still  greater 
degree,  of  the  white  corpuscles  ;  and  believes  that  in  chlorosis  and  an&mia,  espe- 
cially when  there  is  constipation,  cetrarin  will  prove  a  valuable  remedy. 

Lichenin,  or  Lichen  Starch,  the  mucilaginous,  nutritive  principle  of  Iceland 
moss,  differs  from  ordinary  starch  in  not  being  deposited  in  granules  within  the  cells, 
but  in  layers  or  irregular  masses  between  the  cells,  or  indeed  forming  the  walls 
of  the  cells  (De  Bary*) .  In  cold  water  it  swells  up  without  dissolving  ;  in  hot  water 
it  dissolves,  and  on  cooling  condenses  into  a  jelly.  With  iodine  it  strikes  a  yellow, 
green,  or  sometimes  rather  faint  blue,  color.  It  is  found  in  very  many  lichens  ;  also 
in  many  species  of  sea-weed,  notably  in  the  so-called  Corsican  moss. 

Iceland  moss  has  enjoyed  some  reputation  as  a  demulcent  in  pectoral  com- 
plaints. From  its  bitter  principle,  it  is  somewhat  tonic,  and  its  lichenin  is  probably 
about  equal  to  ordinary  starch  as  a  nutrient.  When  prepared  as  an  article  of  diet, 
in  the  form  of  jelly,  the  bitter  taste  should  be  removed  by  soaking  for  some  hours 
in  a  very  weak,  cold  alkaline  solution,  and  afterwards  for  a  little  while  in  cold  water. 

HORDEUM. — The  decorticated  seeds  of  the  common  barley  constitute  the  pearl 
barley  of  commerce.  They  contain  starch  and  mucilage,  and  the  decoction  was 
formerly  official.  Barley  water  is  used  as  a  nutritious,  demulcent  drink  in  fevers 
and  inflammatory  conditions,  especially  when  the  gastric  mucous  membrane  is 
involved.  The  U.  S.  Pharmacopoeia  of  1870  directed  that  it  should  be  prepared  as 
follows:  "Take  of  barley  two  troyounces  ;  water  a  sufficient  quantity.  Having 
washed  away  the  extraneous  matters  which  adhere  to  the  barley,  boil  it  with  half  a 
pint  of  water  for  a  short  time  and  throw  away  the  resulting  liquid.  Then,  having 
poured  on  it  four  pints  of  boiling  water,  boil  down  to  two  pints,  and  strain." 


REFERENCES. 

DEMULCENTS.  a.  DE  BARY Hofmeister's     Handb.     d. 

,.  ROBERT Verhand.d.  Internal.  Med.  Physiol.  Botan..  ii.  »55- 

Cong.,  Berlin,  1890. 

50 


FAMILY   XII.— EMOLLIENTS. 


TRUE  emollients  are  perfectly  bland,  fatty  substances,  which,  when 
applied  to  the  skin,  soften  it  and  render  it  more  pliable.  The  action  of 
these  remedies  is  largely  mechanical,  and  they  probably  soften  the  derm 
in  precisely  the  same  way  as  they  affect  a  raw  hide  or  a  piece  of  leather. 
They  are  therefore  especially  useful  when  the  skin  has  a  tendency  to 
crack  or  to  chap.  Whenever  surfaces  become  sore  by  attrition,  or,  in 
other  words,  chafe,  emollients  are  also  useful  mechanically.  They  often 
afford  relief  in  simple  inflammations  of  the  skin  under  such  circum- 
stances that  their  action  cannot  be  explained  as  purely  mechanical  : 
indeed,  they  seem  to  exert  a  dynamic  influence  upon  the  nutrition  of  the 
parts  concerned.  It  may  be  that  they  shut  out  or  interfere  with  the  de- 
velopment of  pathogenetic  germs,  or,  in  other  words,  that  they  are 
mechanical  antiseptics.  Be  these  things  as  they  may,  clinical  experience 
has  demonstrated  that  fatty  matters  are  of  very  great  value  in  the  treat- 
ment of  superficial  inflammations.  The  blandest  fat,  when  it  becomes 
rancid,  is  very  irritating,  and  will  do  more  harm  than  good,  so  that  the 
strictest  attention  must  be  paid  to  the  condition  of  the  fatty  material 
employed.  Any  perfectly  bland  oily  substance  may  be  used  as  an  emol- 
lient. There  does  not  appear  to  be  any  marked  difference  in  the  power 
of  true  fats  in  penetrating  the  skin,  excepting  in  so  far  that  a  hard  fat 
does  not  readily  melt  at  the  temperature  of  the  body,  and  therefore  does 
not  yield  itself  to  absorption  so  readily  as  does  a  soft  one.  SEVUM,  U.  S. 
Suet. — Mutton  Suet. — The  fat  obtained  from  the  abdomen  of  the  ordinary 
sheep  is  a  white,  solid,  bland  fat,  not  melting  below  45°  C.  (113°  F.), 
and  is  therefore  a  hard  fat,  which  is  used  chiefly  for  the  purpose  of  render- 
ing more  firm  various  ointments.  ADEPS,  U.  S.  Lard. — This  is  a  soft 
fat,  melting  at  about  38°  C.  (100°  F. ).  Ordinary  lard  of  the  market 
contains  salt,  from  which  it  must  be  freed  by  washing  before  it  is  used  for 
medical  purposes.  ADEPS  BENZOINATUS,  U.  S. ,  is  lard  impregnated  with 
two  per  cent,  of  benzoin,  which  acts  as  a  preservative  and  has  no  delete- 
rious influence  whatever  upon  the  skin  or  the  mucous  membranes. 
Spermaceti  (CETACEUM,  U.  S. )  is  employed  to  give  consistence  to  oint- 
ments, as  is  also  wax  (CERA  ALBA,  or  White  Wax,  and  CERA  FLAVA, 
or  Yellow  Wax,  U.  S. ).  Cold  Cream  (UNGUENTUM  AQU^E  ROSJE, 
U.  S. ),  containing  oil  of  sweet  almonds,  spermaceti,  white  wax,  and  rose 
water,  is  one  of  the  most  elegant  of  the  official  emollients. 
786 


EMOLLIENTS.  787 

OLEUM  AMYGDALAE  EXPRESSUM.  U.  S. — Oil  of  Sweet  Almond,  ob- 
tained from  ordinary  sweet  almonds,  Amygdala  Dulcis,  is  a  pale,  straw- 
colored  or  colorless,  almost  inodorous  oil,  having  a  mild,  nutty  flavor. 
The  oil  of  sweet  almond  is  one  of  the  most  delicate  of  the  fixed  oils,  and 
may  be  used  for  making  elegant  emollient  applications  for  the  skin. 

OLEUM  THEOBROMATIS.  U.  S. — Cacao  Butter. — A  whitish,  solid, 
very  bland  vegetable  fat,  which  melts  at  or  about  30°  C.  (86°  F. ),  and 
consequently  lends  itself  to  the  formation  of  suppositories,  which  are  firm 
outside  the  body,  but  when  placed  inside  the  body  melt  freely. 

OLEUM  LINI,  U.  S. ,  or  Linseed  Oil,  is  a  yellowish  oily  liquid,  with  a 
peculiar  odor  and  a  bland  taste.  When  exposed  to  the  air  it  thickens 
and  acquires  a  strong  odor  and  taste.  It  is  the  least  elegant  of  these 
oils,  and  is  not  often  used  in  medicine,  except  when  in  fecal  accumula- 
tions or  other  conditions  large  rectal  injections  of  oil  are  required,  when 
it  is  preferred  on  account  of  its  cheapness. 

OLEUM  OLIV^E,  U.  S. ,  or  Olive  Oil,  is  expressed  from  the  fruit  of  the 
European  olive  ;  has  a  pale  yellow  or  light  greenish-yellow  color,  and  a 
pleasant  odor  and  taste.  It  is  the  ordinary  salad  oil  of  the  table,  and 
may  be  used  wherever  a  very  bland  oil  is  desired.  It  has,  however,  no 
superiority  for  ordinary  purposes  over  the  OLEUM  GOSSYPII  SEMINIS, 
U.  S. ,  or  Cotton-seed  Oil,  which  is  expressed  from  the  seeds  of  the  ordi- 
nary cotton-plant ;  indeed,  a  very  large  proportion  of  the  olive  oil  of 
commerce  is  cotton-seed  oil ;  it  is  credibly  affirmed  that  more  cotton- 
seed oil  is  exported  from  New  Orleans  to  the  Mediterranean  cities  than 
olive  oil  is  exported  from  those  ports,  much  of  the  cotton-seed  oil  coming 
back  with  olive  oil  labels.  There  seems  to  be  no  sufficient  reason  for 
believing  that  olive  oil  differs  from  cotton-seed  oil  in  its  physiological  or 
therapeutic  properties.  These  oils  are  sometimes  used  internally  with 
advantage,  for  nutritive  purposes,  and  are  also  very  mildly  laxative. 
The  assertion,  originally  made  by  Kennedy,  that  large  doses  of  olive  oil 
are  very  useful  against  biliary  calculi,  has  received  strong  clinical  con- 
firmation. S.  Rosenberg1  found  that  in  dogs  with  biliary  fistulae  olive 
oil  not  only  increased  the  amount  of  bile,  but  also  rendered  the  bile 
much  more  liquid.  Since  fats  are  absorbed  chiefly,  if  not  entirely, 
through  the  thoracic  duct,  it  would  appear  that  the  oil  must  pass  through 
the  pulmonary  circulation  before  reaching  the  liver.  This  is  confirmed 
by  the  experiments  of  Chauffard,  who  could  not  find  in  the  bile-duct  or 
gall-bladder  any  trace  of  oil  which  he  had  injected  into  the  stomach  of 
the  dog.  If  olive  oil  has  the  asserted  remedial  influence,  it  probably  acts 
reflexly  through  the  nervous  system, — through  a  mechanism  provided  by 
nature  for  the  purpose  of  aiding  in  the  digestion  of  fats  when  in  excess. 
The  dose  of  the  oil  should  be  not  less  than  from  five  to  seven  ounces 
(150-215  C.c. )  taken  in  four  to  eight  portions  in  not  longer  than  three 
hours.  It  may  be  given  in  aromatized  emulsion,  with  a  little  brandy  or 
whiskey  if  desired. 

The  U.  S.  Pharmacopoeia  recognizes  two  fatty  acids,  namely,  ACIDUM 


788  LOCAL    REMEDIES. 

OLEICUM,  U.  S.  Oleic  Acid  is  a  yellowish  or  brownish  oily  liquid,  having 
peculiar  oil-like  odor  and  taste,  which  is  used  in  medicine  solely  for  the 
preparation  of  the  oleates.  In  the  making  of  an  ordinary  ointment  with 
a  metallic  basis  an  oleate  is  formed,  and  various  practitioners  prefer  the 
chemically  pure  oleate  as  more  certain  and  definite  in  its  action.  In  our 
own  experience,  however,  these  preparations  have  not  seemed  to  have 
any  practical  superiority  over  the  older  ointments.  The  second  fatty  acid, 
Stearic  Acid  (AciDUM  STEARICUM,  U.  S. ),  is  a  hard,  white,  glossy  solid, 
odorless  and  tasteless,  melting  at  69.2°  C.  (156.6°  F. )  It  is  used  in  the 
form  of  stearates. 

ADEPS  LAN^E.  U.  S. —  Wool  fat  is  obtained  from  the  wool  of  sheep, 
which  is  said  to  contain,  on  an  average,  forty-five  per  cent,  of  it.  It 
appears  to  be  practically  the  same  as  the  natural  oil  of  the  hair  in  man 
and  other  animals.*  ADEPS  LAN^E  HYDROSUS,  U.  S. ,  or  Lanolin,  con- 
tains about  thirty  per  cent,  of  water,  and  is  the  form  of  the  unguent  ordi- 
narily employed.  It  was  first  recommended  by  Oscar  Liebreich  as  a 
basis  for  ointments  or  preparations  to  be  applied  to  the  surface  of  the 
skin.  It  is  entirely  free  from  irritant  properties,  has  the  power  of  taking 
up  a  large  amount  of  water  without  losing  its  unctuousness  and  does 
not  easily  become  rancid;  it  has  been  asserted  that  it  is  absorbed  through 
the  skin  much  more  readily  than  are  other  fats.  In  the  experiments  of 
Patschkowsky,2  half  an  hour  after  inunction  with  lanolin  and  potassium 
iodide  the  iodine  was  recognized  from  the  urine,  while  official  potassium 
iodide  ointment  yielded  negative  results.  This  has  been  confirmed  by 
Kaspar,3  but  Ritter  and  Pfeiffer  obtained  contrary  results,  and  in  a  con- 
siderable series  of  experiments  were  unable  to  perceive  that  lanolin  had 
any  superiority  over  other  fats  in  promoting  absorption.  The  facts, 
moreover,  that  lanolin  is  largely  the  secretion  of  sebaceous  follicles,  con- 
tains an  abundance  of  cholesterin,  and  is  in  the  nature  of  a  waste  product 
which  is  intended,  not  for  absorption,  but  for  the  keeping  soft  of  the  skin 
and  its  appendages,  indicate  very  strongly  that  it  will  yield  itself,  and 
medicinal  substances  with  which  it  may  be  impregnated,  less  readily  to 
absorption  than  do  other  fats.  As  a  basis  of  ointments  used  to  medicate 
the  skin  it  is  most  effective,  but  when  absorption  is  desired  it  is  probably 
inferior  as  a  vehicle  to  ordinary  fats. 

GLYCERINUM— GLYCERIN.     U.  S. 

This  is  a  thick,  syrupy  liquid,  colorless,  free  from  odor,  and  of  a 
sweet  taste.  Chemically  speaking,  it  is  propenyl  alcohol.  It  is  always 
set  free  during  the  process  of  saponification,  and  formerly  was  a  by- 
product in  the  manufacture  of  soaps.  At  present  it  is  made  by  the  direct 
decomposition  of  fats  by  superheated  steam. 

Under  certain  circumstances,  not  well  understood,  glycerin  forms 
hard,  brilliant  crystals.  In  its  usual  liquid  form  it  mixes  in  all  propor- 

*  See  Virchow's  Archiv,  1890,  cxxi. 


EMOLLIENTS.  789 

tions  with  water  and  alcohol,  and  itself  dissolves  iodine,  bromine,  the 
alkalies,  tannic  and  other  vegetable  acids,  a  large  number  of  neutral 
salts,  salicin,  and  other  organic  principles.  It  throws,  however,  most 
alkaloidal  salts  out  of  their  watery  solution. 

Glycerin  does  not  evaporate  upon  exposure,  but  is  very  hygroscopic, 
and  absorbs  water  from  the  air.  When  pure,  it  is  incapable  of  becoming 
rancid  or  of  fermenting  spontaneously.  The  acrid  glycerin  owes  its  irri- 
tant properties  to  impurities,  especially  to  oxalic  and  formic  acids;  cheap 
grades  of  glycerin  are  frequently  contaminated  with  arsenic. 

PHYSIOLOGICAL  ACTION. — When  large  doses  of  glycerin  (in  the  dog 
eight  or  more  parts  per  thousand  by  weight)  are  injected  subcutaneously, 
death  is  produced  in  a  period  varying,  according  to  the  dose,  from  one 
hour  to  several  days.  The  symptoms  are  loss  of  muscular  strength, 
lethargy,  bloody  urine,  vomiting,  dryness  of  the  mucous  membrane,  with 
marked  thirst,  fall  of  temperature,  gradual  extinction  of  both  respiration 
and  circulation,  and  finally  convulsions  and  coma  (Dujardin-Beaumetz 
and  Audije"*).  The  convulsions  occur  earlier  and  are  more  severe  when 
large  doses  are  employed,  and  are  then  said  to  be  tetanic,  and  to  be 
accompanied  by  a  decided  rise  of  temperature.  The  fall  of  temperature 
is,  even  in  the  milder  cases,  present  only  late  in  the  poisoning,  and  is 
sometimes,  if  not  always,  preceded  by  a  rise.  After  death  intense  conges- 
tion, with  more  or  less  softening  of  the  tissue,  is  found  in  the  lungs,  kid- 
neys, and  intestines.  So  far  as  we  know,  the  largest  amounts  of  glycerin 
taken  by  the  stomach  in  man  have  produced  no  other  symptoms  than 
those  of  mild  gastro-intestinal  irritation  ;  but  Schellenberg 5  has  reported 
a  long  series  of  cases  in  which  serious,  and  in  one  instance  fatal,  poison- 
ing followed  the  injection  of  glycerin  containing  iodoform,  for  coxitis 
and  other  diseases.  The  conclusion  of  Schellenberg,  that  the  manifesta- 
tions were  due  to  the  glycerin,  is  confirmed  by  the  fact  that  they  were 
those  seen  in  the  lower  animals  poisoned  by  injections  of  glycerin, — 
namely,  loss  of  muscular  strength,  elevation  of  temperature,  rapid  pulse, 
albuminous  bloody  urine  with  tube-casts,  and  in  the  fatal  case  the  lesion 
of  acute  parenchymatous  nephritis. 

Catillon  *  asserts  that  glycerin  administered  in  small  continuous  doses 
exerts  a  decided  effect  upon  nutritioYi,  but  the  general  drift  of  the  present 
evidence  is  to  show  that  glycerin  has  no  distinct  effect  upon  tissue-changes. 

In  Catillon' s  experiments,  eight  grains  given  daily  to  guinea-pigs  caused  a 
very  marked  gain  in  weight,  with  a  lessened  excretion  of  urea.  In  man  an  ounce 
daily  also  produced  a  decided  diminution  in  the  elimination  of  urea,  which  was  not 
increased  by  increasing  the  doses  of  glycerin.  The  appetite  in  many  cases  was, 
after  a  little  time,  much  improved,  and  then  the  increased  ingestion  of  food  pro- 
duced an  increased  elimination  of  urea.  The  fact  that  an  increase  of  food  was  per- 
mitted in  these  experiments  shows,  however,  that  the  conditions  of  experimentation 
were  not  rigid  enough  to  allow  much  weight  to  be  attached  to  the  result ;  and  the 
relation  of  glycerin  to  the  elimination  of  urea  has  been  investigated  by  L.  Lewin,7 
by  N.  Tschirwinsky,8  and  by  I.  Munk,'  with  somewhat  contradictory  results.  Of 
these  experiments  the  most  extensive  are  those  of  Munk,  who  seems  to  have  used 


790  LOCAL    REMEDIES. 

all  proper  precautions,  and  who  found  that  glycerin  has  no  effect  upon  the  elimina- 
tion of  urea  or  upon  the  general  bodily  nutrition.  The  results  reached  by  Lewin 
correspond  with  those  of  Munk.  Tschirwinsky  omitted  fatty  materials  from  the 
food,  and  found  that  while  at  first  the  elimination  of  urea  was  diminished,  it  after- 
wards, under  the  use  of  very  large  doses  of  glycerin,  was  increased. 

Glycerin  is  absorbed  from  the  alimentary  canal,  and  when  freely  ad- 
ministered is  in  part  eliminated  and  in  part  burnt  up  in  the  system. 

Both  Ustimowitsch 10  and  P16sz "  found  a  substance  in  the  urine  which  they 
believe  to  be  a  derivative  product  of  glycerin,  while  Catillon  proved  that  it  is  not 
eliminated  by  the  skin  or,  even  when  it  purges,  by  the  intestines.  Catillon  and 
Lewin  recovered  from  the  urine  only  a  small  proportion  of  that  ingested,  Tschir- 
winsky only  8.7  per  cent.,  while  Ludwig  Arnschink12  found  that  not  more  than 
thirty  per  cent,  escapes  from  the  body.  Since  a  large  proportion  of  ingested 
glycerin  is  oxidized  in  the  body,  it  would  appear  that  it  is  capable  of  replacing 
to  some  extent  true  fatty  carbohydrates  for  the  production  of  heat  or  energy,  and, 
therefore,  has  food  value.  According  to  the  calculations  of  Arnschink,  two  hun- 
dred and  nineteen  parts  of  it  are  equivalent  to  about  one  hundred  parts  of  fat. 
This  view  is  corroborated  by  the  work  of  Scheremetjewsky,  who  found  in  rabbits 
that  the  intravenous  injection  of  glycerin  was  followed  by  an  immediate  increase  of 
the  consumption  of  oxygen,  and  of  the  giving  up  of  carbonic  acid. 

The  work  of  Scheremetjewsky  has  given  rise  to  considerable  contro- 
versy, but  the  latest  experiments,  those  of  I.  Munk,  seem  to  lead  to  the 
conclusion  that  glycerin  is  capable  of  taking  the  place  of  the  bodily  fat.* 

According  to  Fuchsinger, IS  the  bloody  urine  produced  by  poisonous 
doses  of  glycerin  contains  an  abundance  of  the  coloring- matter  of  the 
blood,  but  no  free  corpuscles.  Very  interesting  in  connection  with  the 
use  of  glycerin  in  diabetes  is  the  assertion  of  Fuchsinger,1*  that  in  rab- 
bits slightly  poisoned  with  glycerin  no  sugar  appears  in  the  urine  after 
the  ' '  diabetic  puncture. ' '  The  experiments  of  Eckhard 15  gave,  however, 
a  contrary  result,  and  Catillon  affirms  that  given  in  very  large  continuous 
doses  glycerin  increases  the  amount  of  sugar  in  the  blood. 

THERAPEUTICS. — Locally  applied,  glycerin  is  usually  unirritating, 
and  it  is  much  employed  as  an  emollient.  The  chief  disadvantage  that 
attends  its  use  is  its  stickiness  ;  on  the  other  hand,  its  non-volatility 
and  its  hygroscopic  properties  give  a  persistency  to  its  action  which  is 
often  very  advantageous.  It  enters  largely  into  the  composition  of 
popular  emollient  ointments,  or  "creams,"  as  they  are  called,  and  is 
often  used  itself  for  chapped  hands,  excoriations,  and  similar  troubles. 
It  is  also  employed  by  dermatologists  to  some  extent  in  chronic  eczema  ; 
in  seborrhcea,  whether  affecting  the  hairy  scalp  or  other  parts,  it  is  as- 
serted to  be  especially  useful,  softening  the  masses  of  secretion,  and, 
used  in  conjunction  with  such  remedies  as  borax,  zinc,  and  lead  acetate, 
diminishing  the  amount  of  secretion.  When  there  is  a  want  of  seba- 
ceous secretion,  it  is  said  also  to  act  efficiently  ;  in  scabies,  pruritus, 

*  For  discussion,  see  Archivf.  d.  Ges.  Phys.,  1889-90,  xlvi. 


EMOLLIENTS.  791 

and  even  psoriasis,  glycerin  is  used,  diluted  with  water,  as  a  vehicle  for 
more  active  remedies.  Upon  the  mucous  membranes  glycerin  acts  very 
much  as  it  does  upon  the  skin,  and  diluted  with  water  is  very  useful  in 
coryza,  and  even,  by  enemata,  in  dysentery  ;  in  croup  or  laryngitis  it  may 
with  advantage  be  applied  freely  by  means  of  a  large  camel' s-hair  brush 
to  the  orifice  of  the  larynx,  so  as  to  run  into  the  latter.  In  laxative 
doses  it  is  asserted  to  be  very  effective  in  hemorrhoids.  It  also  forms  an 
excellent  basis  for  mouth-washes  ;  or  a  paste  may  be  made  with  it  and 
borax,  or  similar  substance,  for  use  in  ulcerations  of  the  same  cavity. 
The  list  of  diseases  in  which  this  remedy  is  employed  might  be  very 
much  lengthened  ;  but  the  examples  already  given  are  sufficient  to  indi- 
cate the  range  of  its  application  as  an  emollient  and  as  a  vehicle.  There 
are  certain  persons  upon  whose  skin  and  mucous  membranes  even  the 
purest  glycerin  seems  to  act  as  an  irritant.  This  influence  is  most  intense 
when  the  glycerin  is  nearly  or  entirely  free  from  water.  It  is,  however, 
discernible  even  when  the  remedy  is  much  diluted,  and  often  inhibits  its 
use.  The  existence  of  this  idiosyncrasy  to  glycerin  can  be  determined 
only  by  trial. 

When  administered  internally  in  doses  of  one  or  two  ounces,  glycerin 
acts  as  a  gentle  but  very  uncertain  laxative.  It  was  proposed  many  years 
ago  as  a  substitute  for  cod-liver  oil  in  cachectic  diseases,  but  has  failed  to 
come  into  use.  It  has  also  been  highly  commended  in  diabetes*  but  is 
of  no  service.  It  is  valuable  as  a  harmless  substance  which  has  the 
power  of  disguising  nauseous  medicines.  In  this  way  it  may  be  em- 
ployed with  castor  oil,  in  emulsions  of  turpentine,  in  solutions  of  iron, 
and  in  various  mixtures.  It  seems,  as  it  were,  to  envelop  the  medicinal 
substances  and  prevent  their  acting  on  the  palate.  Plasma  or  Glycerite 
of  Starch  (GLYCERITUM  AMYLI,  U.S.)  is  often  used  as  a  protective; 
Glycerite  of  Yolk  of  Egg  (GLYCERITUM  VITELLI,  U.  S.,  1890)  is  no 
longer  official  in  making  emulsions. 

BENZOSULPHINIDUM.  U.  S.  GLUSIDUM.  Br.— SACCHARIN.f 
Saccharin  is  a  substance  discovered  by  Fahlberg  in  1879.  Chemi- 
cally it  is  an  imide  derived  from  the  toluene  of  coal-tar.  It  occurs  as  a 
white  powder  composed  of  irregular  crystals,  very  slightly  soluble  in 
water,  readily  soluble  in  glycerin,  alcohol,  and  ether.  Its  watery  solu- 
tion has  a  distinctly  acid  reaction,  and  it  forms  salts.  Its  most  remarkable 
property  is  its  sweet  taste,  which  is  said  to  be  three  hundred  times  more 
intense  than  is  that  of  sugar,  so  that  if  one  grain  of  it  be  dissolved  and 
neutralized  in  about  ten  pints  of  water  its  presence  can  still  be  recognized. 
Taken  internally,  saccharin  is  rapidly  absorbed;  it  is  eliminated  unchanged 

*  For  literature  and  discussion  of  point,  see  Ztemssen's  Encyclopedia,  xvi. 

f  The  present  is  probably  as  good  as  any  other  place  in  this  treatise  to  notice  a  sub- 
stance whose  use  in  practical  medicine  depends  upon  its  lack  of  medicinal  properties. 
On  account  of  its  being  a  proprietary  or  patented  drug  it  is  not  recognized  by  the  U.  S. 
Pharmacopoeia. 


792 


LOCAL    REMEDIES. 


chiefly  through  the  kidneys,  Bruylants16  having  recovered  about  eighty 
per  cent,  of  it  from  the  urine.  It  has  been  found  by  Bruylants  in  the 
milk  of  a  nursing  woman,  and  by  Hedley  abundantly  in  the  saliva. 
Its  influence  upon  man  and  animals  is  very  slight ;  Mosso  and  Aducco 
administered  seventy-five  grains  to  a  man  without  sensible  effect,  and 
found  that  frogs  will  live  for  months  in  a  solution  rendered  neutral  with 
soda  ;  also,  that  six  hundred  grains  given  to  a  dog  during  ten  days 
caused  no  change  in  the  daily  renal  excretion  of  water,  urea,  hippuric 
acid,  sulphuric  acid,  or  phosphoric  acid,  and  no  alteration  of  the  weight 
or  of  the  general  health.  On  the  other  hand,  it  appears  to  have  a  feeble 
influence  upon  various  fermentations.  Its  solution  has  antiseptic  prop- 
erties, and  in  Plugge's  numerous  experiments  it  checked  the  action  of 
ptyalin,  pepsin,  trypsin,  and  other  allied  ferments.  Sawitzki,  indeed, 
alleges  that  it  depresses  proteid  metabolism.  |  In  Bruylants' s  trials  it 
failed  to  check  artificial  gastric  digestion,  probably  on  account  of  the 
acidity  of  the  solution,  but  as  little  as  one  per  cent,  is  enough  distinctly  to 
lessen  the  activity  of  pancreatin  solutions.  The  general  innocuousness  of 
saccharin  is,  in  accord  with  our  own  experience,  asserted  by  Salkowski," 
by  Bruylants,  by  Dreschfeld,18  by  Levenstein,19  and  by  other  clinicians. 
Mixed  with  sodium  bicarbonate,  two  parts  to  three,  saccharin  becomes 
soluble.  Its  chief  value  in  practical  medicine  is  as  a  substitute  for  sugar 
in  diabetes,  obesity,  and  other  diseases  in  which  sugar  is  contra-indicated, 
but  the  observation  of  James  Little,20  that  when  freely  given  it  is  of 
great  antiseptic  value  in  the  treatment  of  ammoniacal  urine,  from  cystic, 
phosphatic,  or  other  diseases  producing  retention  or  fermentation,  is 
probably  correct.  It  may  be  used  freely  as  an  article  of  diet,  in  the  form 
of  a  solution  in  glycerin  ;  for  medical  purposes  it  is  sometimes  adminis- 
tered in  compressed  pills  :  dose,  five  grains  (0.3  Gm. ). 

PETROLATUM. — The  solid  basis  of  petroleum  is  paraffin,  and  after  the 
distillation  of  the  more  volatile  portions  of  the  petroleum  there  are  left 
mixtures  sold  as  vaseline,  cosmoline,  etc.,  whose  consistency  varies  in 
proportion  to  the  amount  of  the  liquid  hydrocarbon  left  in  them.  Such 
substances  are  PARAFFINUM,  U.  S. ,  a  solid,  colorless  mass;  PETROLA- 
TUM, U.  S.,  popularly  called  vaseline,  a  yellowish  to  whitish  amber  oint- 
ment-like mass;  PETROLATUM  ALBUM,  U.  S. ,  a  white  unctuous  mass; 
PETROLATUM  LIQUIDUM,  U.  S. ,  a  colorless  or  yellowish  liquid.  All  the 
cosmolines  are  insoluble  in  water,  do  not  become  rancid,  are  free  from 
irritating  properties,  and  act  mechanically  on  the  skin  like  fats.  They 
are  used  as  local  emollient  applications  to  the  skin  and  mucous  mem- 
branes and  as  a  basis  for  ointments.  When  taken  internally  in  the  dose 
of  a  drachm  to  an  ounce  they  exert  no  influence  upon  the  system,  but  act 
locally  upon  the  mucous  membrane  of  the  alimentary  canal,  allaying  irri- 
tation and  provoking  soft  fecal  discharges. 

*  See  Sajous's  Annual,  1891. 


EMOLLIENTS.  793 

KAOLIN.  U.  S.— Porcelain  Clay.— Fuller' s  Earth.— A  white  pow- 
dery clay,  unctuous  when  moist,  a  hydrated  aluminum  silicate.  It  is 
largely  used  in  the  arts  for  the  purpose  of  clarifying  and  decolorizing  oils 
and  other  fluids.  It  is  a  non-irritant,  inert  substance,  which  is  well  fitted 
for  thickening  ointment  or  paste.  It  enters  into  the  official  Cataplasma 
Kaolini,  U.  S.  Cataplasm  of  kaolin,  a  thick,  paste-like  substance  con- 
taining in  round  numbers  fifty-two  per  cent,  of  kaolin,  4.5  per  cent,  of 
boric  acid,  one-tenth  of  one  per  cent,  of  thymol,  and  one-twentieth  of 
one  per  cent,  of  methyl-salicylate  and  oil  of  peppermint  each,  held  to- 
gether with  glycerin.  A  vast  amount  of  nonsensical  rubbish  has  been 
written  and  believed  of  the  virtues  of  this  paste.  It  possesses  however  no 
virtues  that  do  not  belong  to  the  flaxseed  poultice  and  is  probably  even 
less  efficient. 

POULTICES. — Poultices  are  moist,  soft,  scarcely  adhesive,  perfectly 
bland  plasters,  used  to  a  very  great  extent  to  combat  superficial  inflam- 
mation. Poultices  are  much  more  powerful  agents  than  are  the  true  fatty 
emollients,  and  are  correspondingly  more  capable  of  being  abused  :  the 
results  of  such  abuse  will  be  spoken  of  directly.  A  poultice  may,  of 
course,  be  stimulating  and  irritant  if  made  of  such  a  substance  as  mus- 
tard ;  but  the  ordinary  emollient  or  true  poultice  is  prepared  out  of  some 
bland  material  which  is  totally  free  from  action  upon  the  skin,  and  de- 
pends for  its  remedial  power  solely  upon  the  warmth  and  the  water  which 
it  contains.  Water,  when  pure  and  of  a  temperature  approximating  that 
of  the  body,  is  a  sedative,  checking  all  action,  possibly  by  a  direct  in- 
fluence, but  probably  by  the  merely  mechanical  acts  of  dilution  of  the 
pabulum  and  of  separation  of  the  germinal  granules.  It  is  also  a  relax- 
ant, rendering  all  tissues  soaked  in  it  soft  and  yielding. 

Poultices  are  sometimes  applied  in  the  early  stages  of  phlegmonous 
and  other  superficial  inflammations,  for  the  purpose  of  checking  the 
morbid  action.  Their  influence  is  in  such  case  simply  one  of  sedation, 
and  they  are  certainly  not  so  efficient  as  the  cold-water  dressing.  They 
are,  however,  especially  useful  in  the  advanced  stages  of  inflammation, 
when  suppuration  has  already  commenced  or  is  about  to  set  in.  Clini- 
cal experience  has  demonstrated  that  they  then  favor  the  formation  of 
pus.  Further,  the  poultice  in  the  latter  stages  of  a  superficial  phleg- 
mon not  only  hastens  the  formation  of  pus  in  the  inflammatory  focus, 
but  lessens  irritation  in  the  outlying  parts  by  its  sedative  action,  and 
so  softens  the  tissues  as  to  aid  in  the  passage  outward  and  the  discharge 
of  the  inflammatory  products.  When  poulticing  is  too  long  persisted 
in,  the  part  becomes  pale  or  white,  swollen,  relaxed,  and  has  a  sodden 
look  ;  the  granulations  of  the  ulcer  or  abscess  are  large,  pale,  and  very 
flabby,  and  all  the  vital  actions  are  below  the  normal  point.  It  is  pos- 
sible that  even  death  of  a  part  might  be  brought  about  by  continuous 
poulticing.  Be  this  as  it  may,  after  the  discharge  of  pus,  whenever 
the  parts  put  on  the  aspect  just  spoken  of,  the  poultice  should  be  re- 
moved and  stimulating  applications  substituted. 


794  LOCAL   REMEDIES. 

Any  material  which  is  in  itself  physiologically  inert,  and  will  long 
retain  water,  may  be  used  as  the  basis  of  the  poultice.  Flaxseed  meal  is 
cheap,  and  is  probably  the  most  used  of  any  substance.  Ground  slip- 
pery elm  makes  a  very  elegant  mucilaginous  poultice.  Ordinary  Indian- 
meal  mush  is  often  used.  The  bread  and  milk  poultice  is  non-irritating, 
but  is  prone  to  undergo  putrefaction.  The  poultice  is  rarely  aseptic, 
and  is  often  a  carrier  of  germs.  This  in  a  measure  may  be  prevented  by 
boiling  the  poultice  just  before  putting  it  on  ;  but  even  with  this  pre- 
caution, when  applied  to  an  infected  wound,  poultices,  by  retaining  and 
stimulating  the  growth  of  germs,  often  increase  the  inflammation.  For 
this  reason  other  methods  of  applying  warmth  and  water  have  largely 
replaced  the  old-fashioned  poultice.  Spongiopiline,  or  absorbent  cotton, 
or  similar  material,  which  is  readily  rendered  aseptic,  and  is  incapable  of 
undergoing  fermentation,  when  saturated  with  heat  and  water  affords  an 
application  which  is  practically  a  poultice,  and  which  may  be  rendered 
germicidal  by  the  addition  of  minute  quantities  of  corrosive  sublimate  or 
similar  substances,  as  called  for  by  the  exigencies  of  the  case. 

Poultices  are  frequently  used  in  the  treatment  of  deep-seated  inflam- 
mations. Under  these  circumstances,  according  to  the  dictates  of  ex- 
perience, they  should  be  applied  very  hot,  and  be  frequently  renewed  ; 
very  often,  too,  a  small  amount  of  mustard  or  of  some  similar  stimulating 
material  is  added  to  them  with  advantage.  As  a  result,  these  poultices 
act  as  gentle  but  deep-reaching  counter-irritants,  which  in  all  likelihood 
affect  not  merely  the  blood-vessels  ot  the  skin,  but  also  those  of  the 
subdermal  tissue.  When  it  is  borne  in  mind  that  in  all  these  cases  the 
poultice  is  applied  to  a  very  large  surface,  it  will  readily  be  perceived 
that  this  counter-irritation  is  a  powerful  one.  Thus,  in  pleurisy  or  in 
pneumonia  the  whole  anterior  or  posterior  surface  of  the  chest  is 
covered,  or  perhaps  the  whole  chest  is  enveloped,  by  the  jacket-poultice. 
In  peritonitis  the  poultice  should  be  as  large  as  the  abdomen  of  the 
patient.  In  either  of  these  cases  the  amount  of  blood  drawn  to  the 
surface  must  be  considerable.  It  is  probable  that  the  water  of  the 
poultice  in  some  cases  actually  soaks  through  and  exerts  its  direct 
sedative  influence  upon  the  affected  tissue.  The  value  of  poultices  in 
lung  diseases  is  much  greater  in  children,  whose  chest-walls  are  very 
thin,  than  in  adults  ;  and  it  is  not  illogical  to  believe  that  the  difference 
may  be  dependent  upon  the  inequality  of  the  chest-walls. 

The  jacket-poultice  should  be  made  of  thin  flannel  formed  into  a  sort  of  double 
bag,  so  cut  and  shaped  as  to  fit  the  individual,  and  secured  in  front  with  safety-pins 
and  over  the  shoulders  with  tapes,  or  it  may  be  fastened  directly  to  an  undershirt, 
a  piece  of  oiled  silk  always  being  placed  directly  outside  of  the  jacket.  The  jacket 
should  be  divided  into  two  parts  by  a  horizontal  line  of  stitching,  and  be  filled  from 
one  end.  In  order  to  prevent  sagging  of  the  contents,  it  is  well,  after  filling,  to 
take  a  stitch  here  and  there,  in  the  manner  of  quilting.  The  effect  of  a  jacket- 
poultice  may  be  imperfectly  attained  by  covering  the  patient  with  wool  batting  and 
oiled  silk  outside  of  this, — in  fever  patients  the  moisture  from  the  surface  and  the 
heat  of  the  body  serving  to  form  a  kind  of  fomentation. 


EMOLLIENTS. 


795 


The  value  of  the  jacket-poultice  in  disease  is,  however,  greatly 
lessened  by  the  fact  that  it  enormously  increases  the  heat-retention  of 
the  body,  and  has,  therefore,  in  many  cases  a  very  serious  influence  in 
heightening  a  fever  temperature  whose  reduction  is  urgently  indicated. 
Whenever,  in  a  pneumonia,  the  temperature  is  high,  the  application  of 
cold  water  by  means  of  compresses,  or  absorbent  cotton,  is  preferable  to 
the  use  of  the  jacket-poultice.  In  cases  of  peritonitis  the  sensations  of 
the  patient  are  often  a  practical  guide  to  the  choice  of  the  dressing.  If 
the  pain  is  aggravated  by  external  warmth,  the  cold-water  dressing  is 
preferable  ;  whilst,  if  the  cold-water  dressing  is  steadily  obnoxious  to 
the  patient,  the  best  results  may  usually  be  achieved  by  the  use  of  hot 
water. 


EMOLLIENTS. 


REFERENCES. 

12.  ARNSCHINK 


1.  ROSENBERG   .   .   .  S.  Jb.,  1890. 

2.  PATSCHKOWSKY  .  Pharm.  Zeit.,  1885. 

3.  KASPAR D.  M.  W.,  Dec.  1885. 

4.  DUJARDIN-BEAUMETZ  and  AUDIJ£  .  B.  G.  T., 

xci.  62. 

5.  SCHELLENBERG     .  A.  K.  C.,  1894,  xllX. 

6.  CATILLON  .  .   .   .  B.  G.  T.,  xcii.  130;  A.  de 

P..  1877- 

7.  LEWIN Z.  B.,  xv. 

8.  TSCHIRWINSKY    .  Z.  B.,  xv. 

9.  MUNK   .....  V.  A.  P.  A.,  Ixxvi.  130. 

10.  USTIMOWITSCH    .  A.  G.  P.,  xiii.  453. 

11.  PL6sz A.  G.  P.,  xvi.  153. 


13.  FUCHSINGER  . 

14.  FUCHSINGER  . 

15.  ECKHARD     .    . 

16.  BRUYUANTS   . 

17.  SALKOWSKI    . 

18.  DRESCHFELD 

19.  LEVENSTEIN 

20.  LITTLE    .  .  . 


.  Sitzungsb.  Gesellsch.  Mor- 
phol.  Physiol.,  Miinchen, 
1886,  ii.;  Z.  B.,  xxiii. 

4I3- 

.  A.  G.  P.,  xi.  502. 
.  A.  G.  P.,  xii.  501;  C.  M. 

W.,  1877. 

.  C.  M.  W..  1876,  273. 
.  B.  A.  R.  B.,  1888. 
.  V.  A.  P.  A.,  cv.  46. 
.  Birmingham  Med.  Journ.. 

1886,  409. 

.  Journ.  Soc.  of  Chem..  1886. 
.  Trans.    Royal      Acad.    of 

Med.,  Ireland,  1888,  vi. 


FAMILY   XIIL— PROTECTIVES. 


IN  the  present  class  are  included  those  materials  used  by  the  physi- 
cian as  protective  applications  to  the  skin. 

Adhesive  plaster  (EMPLASTRUM  ADH^ESIVUM,  U.  S. )  is  used  for  me- 
chanical purposes.  It,  however,  irritates  the  skin  somewhat,  and  con- 
sequently is  rarely  employed  where  protection  is  the  only  object.  Under 
the  latter  circumstances,  the  lead  plaster  (EMPLASTRUM  PLUMBI,  U.  S. ) 
or  the  soap  plaster  (EMPLASTRUM  SAPONIS,  U.  S. )  is  preferable.  These 
substances  are  free  from  irritant  properties,  but  are  only  slightly  adhesive, 
and  are  scarcely  used  except  to  protect  the  skin  from  pressure  or  friction, 
as  when  bed-sores  are  threatened.  They  should  be  spread  upon  very  soft 
kid.  It  is  important  that  they  be  not  so  thick  or  hard  as  to  lose  their 
pliability.  If  they  are  stiff,  by  their  movements  during  the  motions  of 
the  body  they  may  do  much  harm.  Isinglass  Plaster  is  readily  applied 
when  simply  dampened,  and  is  much  used  domestically  under  the  name 
of  court  plaster.  Collodion  (COLLODIUM),  U.  S. )  is  a  solution  of  pyrox- 
ylin in  alcohol  and  ether,  pyroxylin  (PYROXYLINUM,  U.  S. )  being  soluble 
gun-cotton,  chiefly  made  up  of  the  tri-  and  tetra-nitro-cellulose  ;  upon 
evaporation  collodion  leaves  on  the  skin  an  adherent  protecting  film. 

Physiologically,  gun-cotton  is  inert.  Collodion  is  a  colorless,  slightly 
opalescent  liquid,  of  a  syrupy  consistence,  and  smelling  strongly  of 
ether.  By  long  standing  it  deposits  a  layer  of  fibrous  matter,  and 
becomes  more  transparent.  This  layer  should  be  reincorporated,  by 
agitation,  before  the  collodion  is  used.  When  it  is  applied  to  the  skin, 
and  the  menstrua  are  allowed  to  evaporate,  collodion  forms  an  impervious, 
colorless,  transparent,  flexible,  and  strongly  contractile  film,  which  ad- 
heres very  closely,  and  cannot  readily  be  removed.  The  contractility  of 
the  film  may  in  a  great  measure  be  destroyed  by  the  addition  to  the  col- 
lodion of  certain  substances,  as  in  flexible  collodion  ( COLLODIUM  FLEX- 
ILE, U.  S. ),  which  contains  five  per  cent,  of  Canada  turpentine  and  three 
per  cent,  of  castor  oil,  and  on  evaporation  leaves  a  film  which  does  not 
contract.  A  collodion  may  be  rendered  actively  medical  by  the  addition 
of  some  principle  soluble  in  its  menstruum,  as  in  cantharidal  collodion. 

As  a  substitute  for  collodion  the  non-official  solution  of  gutta-percha 
in  chloroform  ( LIQUOR  GUTTA-PERCHA)  is  sometimes  employed. 
796 


DIVISION  II.— EXTRANEOUS  REMEDIES. 


THESE  are  drugs  which  are  employed  not  to  act  directly  upon  the 
human  system  or  upon  any  of  its  tissues,  but  upon  some  extraneous 
material  or  entity  either  in  the  cavities  of  the  body  or  upon  its  exterior. 
Thus,  an  antacid  neutralizes  acid  in  the  stomach,  or  an  anthelmintic 
kills  the  tapeworm  in  the  intestines,  or  a  disinfectant  destroys  poisonous 
emanations  in  the  exterior  world  and  thereby  wards  off  disease. 


FAMILY   I.— ANTACIDS. 

ANTACIDS  are,  strictly  speaking,  substances  which  are  capable  of 
neutralizing  acid.  The  class,  as  here  defined,  contains  those  remedies 
which  in  medicine  are  used  for  the  purpose  of  neutralizing  an  excess  of 
acidity  in  the  primae  viae.  They  are  almost  solely  employed  in  forms  of 
dyspepsia.  Without  doubt,  cardialgia,  gastric  uneasiness,  heartburn, 
and  the  rising  of  sour  water  in  the  mouth  are  often  the  result  of  too 
much  acid  in  the  stomach,  perhaps  secreted  by  a  perverted  glandular 
action,  but  more  probably  in  the  great  majority  of  cases  formed  by  fer- 
mentative changes  in  the  partially  digested  food.  As  excessive  acidity 
of  the  stomach  causes  gastric  uneasiness  and  derangement,  so  will  a 
similar  condition  of  the  intestinal  canal  cause  pain  and  spasm  and  func- 
tional disturbance  in  the  bowels.  This  is  seen  most  frequently  in  infants, 
and  is  very  often  associated  with  a  diarrhoea  in  which  the  passages  have 
a  green  color,  similar  to  that  of  spinach,  and  hence  are  sometimes  spoken 
of  as  "spinach-stools."  In  diarrhoea  of  this  character,  as  well  as  in 
colic,  antacids  are  often  of  service  by  neutralizing  the  acid  in  the  intes- 
tinal canal. 

Clinical  experience  has  demonstrated  that  dyspepsia  is  often  perma- 
nently relieved  by  the  use  of  alkalies  when  they  are  given  steadily  day 
after  day,  about  twenty  minutes  after  eating,  for  a  long  time.  Accord- 
ing to  Thomas  K.  Chambers,1  this  is  dependent  upon  an  effect  pointed 
out  by  Claude  Bernard, — the  augmentation  of  the  acid  gastric  juice,  and 
so  of  the  normal  peptic  powers  of  the  stomach.  The  same  authority 
further  says,  ' '  The  test  of  benefit  being  derived  from  an  alkali  is  the 
dose  not  requiring  to  be  increased  as  the  patient  goes  on  taking  it,  but, 

797 


798  EXTRANEOUS    REMEDIES. 

on  the  contrary,  being  diminished  gradually,  while  relief  from  the  recur- 
rence of  heartburn  continues  still  to  be  experienced." 

Sick  headache  is  sometimes  dependent  upon  gastric  irritation  pro- 
duced by  an  excess  of  acid  in  the  stomach.  This  true  sick  headache  is 
generally  to  be  distinguished  from  migraine  by  the  early  occurrence  of 
the  stomach  symptoms,  either  as  heartburn,  nausea,  vomiting,  or  simple 
gastric  distress,  and  by  the  fact  that  the  pain  comes  on  with  an  attack  of 
blindness  or  of  dizziness,  and  is  not  limited  to  any  one  spot,  as  the  supra- 
orbital  or  other  neuralgic  foci,  but  is  felt  all  across  the  brows.  In  this 
form  of  cephalalgia  antacids  often  afford  prompt  relief. 

Various  substances  which  have  already  been  discussed  in  this  work 
are  excellent  antacids,  most  of  them  uniting  this  to  other  medicinal  prop- 
erties. Thus,  when  a  stimulating  antacid  is  desired,  as  is  very  often  the 
case  in  sick  headache,  half  a  drachm  of  the  aromatic  spirit  of  harts- 
horn may  be  taken,  well  diluted  with  water.  Again,  when  a  laxative 
antacid  is  needed,  a  teaspoonful  to  a  tablespoonful  of  magnesia  may  be 
exhibited.  Potassa  and  its  carbonates  have  already  been  dwelt  upon 
with  sufficient  detail.  They  may  be  used  as  antacids  ;  but,  as  they  exert 
other  powerful  influences  upon  the  system,  they  are,  we  think,  not  so 
generally  useful  as  the  soda  preparations. 

SODIUM. 

Pure  soda  is  an  escharotic,  and  most  of  its  salts  are  irritant.  It  is 
absorbed  and  eliminated  freely.* 

Soda  being  the  only  alkali  of  the  blood,  even  very  large  doses  of  it 
have  very  little  influence  upon  man  or  mammalia,  but  it  is  probable  that 
it  acts  much  more  powerfully  on  cold-blooded  animals. 

Grandeau 3  found  that  one  hundred  and  seven  grains  of  sodium  carbonate  in- 
jected into  the  vein  of  a  dog  produced  only  very  slight  symptoms,  and  that  thirty- 
five  grains  of  the  nitrate  similarly  administered  to  a  rabbit  caused  only  some  con- 
vulsive movements.  According  to  Guttmann,4  however,  the  sodium  salts  thrown 
directly  into  the  blood  in  very  large  amounts  will  slowly  cause  death,  the  agony 
being  very  prolonged,  and,  when  the  chloride  is  used,  convulsions  being  developed. 
Both  Podocaepow  and  Guttmann  assert  that  even  the  largest  doses  do  not  sensibly 
affect  the  heart  or  the  temperature  ;  and  the  latter  observer  further  declares  that 
they  are  without  influence  upon  the  nerve-centres,  the  peripheral  nerves,  or  the 
muscles.  But  if  this  be  the  case,  it  is  difficult  to  perceive  how  they  can  cause 
death  ;  and  the  earlier  experiments  of  Podocaepow  indicate  that  they  do  exert  a 
very  feeble  action  upon  the  peripheral  nerves  or  the  muscles.  Curci 5  also  finds  that 
the  sodium  salts  increase  the  blood-pressure  after  the  destruction  of  the  oblongata, 
and  believes  that  they  influence  the  peripheral  vaso-motor  nerves.  H.  G.  Beyer,8 
as  the  result  of  experiments  made  upon  terrapins,  comes  to  the  conclusion  that 
sodium  salts  excite  first  the  ganglia  of  the  vaso-dilator  nerves  and  afterwards  those 
of  the  vaso-motor  nerves. 

*  As  Rabuteau 2  found  that  in  dogs  with  gastric  fistula  both  the  quantity  and  the 
acidity  of  the  gastric  juice  are  decidedly  increased  by  the  use  of  salt  meat,  it  would  appear 
probable  that  the  local  action  of  common  salt  upon  the  stomach  is  that  of  a  stimulant. 


ANTACIDS.  799 

Although  Mayet '  affirms  that  sodium  chloride  increases  the  elasticity 
of  the  red  blood- corpuscles,  the  immediate  influence  of  the  sodium  salts 
upon  the  blood  *  is  probably  very  slight,  since,  according  to  Podocaepow,8 
one  part  dissolved  in  twelve  parts  of  blood  does  not  affect  either  the 
physical  characters  of  the  red  corpuscles  or  the  intensity  of  the  ozone 
reaction. 

Podocaepow  and  Schonlein9  both  affirm  that  they  cause  in  the  frog  spinal  con- 
vulsions, but  in  Ringer  and  H.  Sainsbury's 10  experiments  the  influence  of  the 
sodium  salts  upon  the  frog  was  found  to  be  so  slight  that  they  could  hardly  be 
made  to  kill.  It  seems  established,  however,  that  they  will  produce  cataracts  in 
the  frog.f  Most  observers  state  that  the  sodium  salts  are  capable  of  arresting  the 
frog's  heart  in  diastole,  either  when  it  is  in  position  or  after  it  is  removed  from  the 
body ;  and  Laffout"  states  that  there  Is  a  primary  period  of  cardiac  stimulation, 
which  is  in  accordance  with  the  observation  of  T.  VV.  Mills l'2  upon  fishes.  There 
is,  however,  much  difference  of  statement  by  different  observers  in  regard  to  the 
action  of  these  salts  upon  the  frog's  heart.  J 

Nutrition. — A  certain  amount  of  soda  is  a  necessary  food  for  the 
higher  animals,  yet  it  is  very  doubtful  whether  an  habitual  excess  has 
decided  effect  upon  the  nutrition,  the  general  drift  of  the  present  evi- 
dence being  to  show  that  when  in  excess  the  sodium  salts  neither  increase 
nor  yet  decrease  the  elimination  of  urea  or  other  products  of  tissue- 
waste. 

In  the  experiments  of  Munch  1$  the  continuous  exhibition  of  large  doses  of  com- 
mon salt  to  man  apparently  produced  at  first  a  slight  diminution  of  excretion  and  a 
corresponding  gain  of  the  body  in  weight ;  but  after  a  time  the  excretion  increased 
and  the  weight  of  the  body  decreased.  The  variations  in  excretion  affected  chiefly 
the  urine,  but  sometimes  the  perspiration  and  faeces  were  also  influenced.  The 
urine  was  rendered  alkaline,  but  its  solid  ingredients  were  scarcely  at  all  affected. 
The  conclusion  of  Damourette  and  Hyades,1*  that  salt  increases  the  elimination  of 
urea  and  uric  acid,  is  not  warranted  by  their  own  experiments ;  and  in  the  re- 
searches of  I.  Mayer,15  of  A.  Ott,18  of  C.  Clar,"  and  of  L.  Klemptner,18  neither  the 
sodium  citrate,  acetate,  phosphate,  or  sulphate  increased  nitrogenous  elimination, 
whilst  in  those  of  Dalebe  and  Carberet"  the  alkaline  sodium  salts  reduced  the 
output  of  urea. 

THERAPEUTICS. — The  fact  that  soda,  in  moderate  amount,  has  no  de- 
pressing action,  and  indeed  very  little,  if  any,  influence  upon  the  general 

*  Kowalewsky  records  in  the  Centralbl.f.  Med.  Wissen.,  1887,  the  results  of  an  elab- 
orate study  of  the  effects  of  adding,  either  in  solid  form  or  in  concentrated  solution,  salts 
of  potassium,  sodium,  lithium,  and  ammonium  to  the  blood.  As  it  is  not  possible  at 
present  to  connect  this  influence  with  the  effects  of  therapeutic  doses  of  the  drug  inside 
of  the  body,  we  content  ourselves  with  referring  to  the  paper. 

t  For  a  discussion  of  this,  and  literature  on  the  subject,  see  Limbourg  (Arch./. 
Exper^.  Path.  u.  Pharm.,  1888,  xxiv.).  For  a  series  of  papers  on  the  antagonistic  actions 
of  sodhim,  potassium,  and  calcium  salts  on  the  frog,  by  Sydney  Ringer,  see  Journal  of 
Physiology,  1890,  1894,  1895. 

|  See  Podocaepow  (Virchow's  Archiv,  xxxiii.  507),  Schonlein  (Arch.  f.  d.  Ges. 
Physio!.,  xviii.  26),  Laffout  (Compt.-Rend.  Soc.  Biol.,  1880,  282),  Ringer  and  Sainsbury 
(Lancet,  1882,  ii.  736),  Ringer  (Brit.  Med.  Journ.,  1884).  Limbourg  (Arch.  f.  Exper. 
Path.  u.  Pharm.,  1888,  xxiv.). 


8oo  EXTRANEOUS    REMEDIES. 

system,  renders  it  preferable  to  potash  in  cases  of  acidity  of  the  primae 
viae.  It  is  par  excellence  the  alkali  for  acid  dyspepsia.  On  the  other 
hand,  the  circumstance  clearly  established  by  Roberts,19  that  it  is  less 
powerful  as  a  solvent  of  uric  acid  than  is  its  sister  alkali,  together  with  the 
property,  believed  to  belong  in  a  much  greater  degree  to  potash,  of  pre- 
venting the  formation  of  uric  acid,  makes  soda  of  very  inferior  value  in 
uric  acid  gravel  or  uric  acid  diathesis.  When  in  any  case  it  is  desirable 
simply  to  render  the  urine  alkaline,  and  at  the  same  time  to  avoid  de- 
pressing the  system  generally,  soda  would,  on  theoretical  grounds  at  least, 
seem  preferable. 

It  appears  to  be  well  proved,  clinically,  that  the  alkaline  sodium 
salts  given  one  to  two  hours  before  meals  in  full  doses  are  of  decided 
value  in  the  treatment  of  chronic  hepatic  torpor,  of  catarrhal  jaundice,  and 
especially  of  gall-stones  or  other  affections  associated  with  excessive 
viscidity  of  the  biliary  secretions. 

As  the  result,  however,  of  an  elaborate  series  of  experiments  made  upon  dogs 
with  biliary  fistula,  J.  Glass  *°  concludes  that  the  alkalies  given  by  the  mouth  do  not 
increase  the  alkalescence  or  amount  of  the  bile.  The  caution  necessary  in  apply- 
ing such  experiments  to  human  medicine  has  been  spoken  of  in  an  earlier  chapter. 
Moreover,  it  was  apparently  proved  by  the  experiments  of  S.  W.  Lewaschen  that 
the  sodium  carbonate,  sulphate,  or  phosphate,  given  to  dogs  with  biliary  fistula, 
increases  very  markedly  the  liquidity  of  the  bile  by  diminishing  the  percentage  of 
solids.  The  sodium  salicylate  acted  similarly  to,  but  much  more  powerfully  than, 
the  other  salts.  E.  Dufourt,  experimenting  with  the  sodium  bicarbonate  upon 
dogs,  found  that  there  was  a  very  constant  and  pronounced  increase  both  of  the 
glycogen  and  of  the  sugar  of  the  liver. 

A  possible  therapeutic  use  of  sodium  carbonate  is  suggested  by  the 
experiments  of  W.  H.  Howell,80  who  found  that  in  the  lower  animals  in- 
travenous or  rectal  injections  of  solutions  of  sodium  carbonate  increase 
markedly  in  animals  suffering  from  shock  the  amplitude  of  the  heart- 
beat, and  cause  a  rise  of  arterial  pressure.  Dalebe  and  Carteret Sl  affirm 
that  in  diabetes,  especially  of  the  azoturic  form,  sodium  carbonate  is  a 
very  valuable  remedy. 

Although  so  harmless,  the  sodium  salts  when  in  great  excess  are  de- 
cidedly irritant,  and  it  has  been  shown  by  Stokvis 21  and  Levi '"  that  it  is 
possible  with  the  sodium  chloride  to  produce  albuminuria,  tube-casts,  and 
organic  renal  changes. 

The  following  are  the  antacid  preparations  of  soda  ;  the  pure  bicar- 
bonate should  usually  be  selected,  as  being  the  least  irritant. 

Soon  HYDROXIDUM.  U.  S. — Caustic  Soda  occurs  in  grayish-white 
fragments,  which  deliquesce  on  exposure  and  subsequently  absorb  car- 
bonic acid.  It  is  an  active  escharotic.  The  five  per  cent,  solution  of 
soda  (LIQUOR  SODII  HYDROXIDI,  U.  S. )  has  a  specific  gravity  of  1.056, 
and  is  too  acrid  for  practical  use. 


ANTACIDS.  801 

SODII  CARBONAS  MONOHYDRAS.  U.  S. — Sodium  Carbonate  occurs 
in  strongly  alkaline,  colorless  crystals,  which  rapidly  effloresce  on  ex- 
posure to  the  air,  and  fall  into  a  white  powder.  It  is  very  soluble 
in  water;  by  heat  its  water  of  crystallization  is  driven  off,  and  the  Dried 
Carbonate  is  left.  Commercial  Sodium  Bicarbonate  (Soon  BICARBONAS 
VENALIS)  is  a  white,  opaque  powder,  containing  variable  amounts  of 
soda  not  fully  saturated  with  carbonic  acid.  Pure  Sodium  Bicarbonate 
(Soon  BICARBONAS,  U.  S. )  should  always  be  selected  for  internal  use. 
The  antacid  dose  of  these  preparations  is  ten  to  twenty  grains  (0.6- 
1.2  Gm. ). 

Sodium  Nitrate  (Soon  NITRAS,  U.  S.)  and  Sodium  Acetate  (Soon 
ACETAS,  U.  S. )  are  never  used  in  medicine. 

CALX— CALCIUM. 

When  calcium  carbonate  (marble,  limestone)  has  its  carbonic  acid 
driven  off  by  heat,  certain  white  or  grayish- white  masses  are  left,  consti- 
tuting the  unslaked  lime  of  commerce  (CALX — Lime,  U.  S. ).  When  to 
this  lime  is  added  about  half  its  weight  of  water,  there  is  formed  a  white 
powder,  calcium  hydrate,  or  slaked  lime. 

Unslaked  lime  is  an  active  escharotic  ;  slaked  lime  is  an  irritant,  or, 
when  in  concentrated  form,  a  feeble  escharotic. 

Lime  is  never  used  in  substance  in  medicine,  but  in  the  form  of  a 
watery  solution.  When  in  such  dilute  form  it  acts  as  a  detergent  and 
sedative,  especially  to  mucous  membranes.  Its  official  insoluble  prepara- 
tions are  free  from  irritant  properties  and  are  mild  astringents.  Neither 
the  soluble  nor  insoluble  preparations  of  lime  are  absorbed  to  any  large 
extent,  the  lime  escaping,  if  given  in  considerable  dose,  in  great  part  with 
the  faeces  in  the  form  of  some  insoluble  salt.  Minute  quantities  of  it 
probably  circulate  in  the  blood  in  combination  with  proteids. 

When  a  soluble  salt  of  calcium  is  given  intravenously,  an  insoluble 
form  of  lime  is  probably  rapidly  deposited  in  the  tissue.  Excretion  of 
lime  chiefly  takes  place  through  the  urine,  or  perhaps  more  largely 
through  the  large  intestine. 

PHYSIOLOGICAL  ACTION. — Probably  owing  to  the  difficulty  of  their 
absorption,  even  the  soluble  preparations  of  lime  have  not  been  found 
in  practical  medicine  to  have  any  general  effect  upon  the  body.  Carl 
Franke,  indeed,  states  that  the  intravenous  injection  of  large  amounts  of 
soluble  lime  salts  has  no  effect  upon  rabbits. 

The  soluble  salts  of  lime  are  evidently  not  without  physiological  activity,  and 
have  close  relation  with  the  general  bodily  well-being.  W.  H.  Howell  and  E. 
Cooke"  have  proved  that  the  inorganic  salts  of  the  blood,  milk,  gastric  juice,  etc., 
are  able  to  keep  the  isolated  frog's  heart  beating  with  force  and  regularity  for 
many  hours  without  other  food,  and,  according  to  the  experiments  of  Ringer, 
among  these  salts  those  of  lime  are  especially  important.  Further,  it  seems  to  be 
demonstrated  that  small  doses  of  soluble  calcium  salts  increase  the  energy  of  the 


802  EXTRANEOUS    REMEDIES. 

heart's  action,  as  the  experiments  of  Ringer "  have  been  confirmed  by  Mickwitz 
and  also  by  Binet.  Langendorff  and  Hueck S2  believe  that  their  own  and  previous 
experiments  justify  the  conclusion  that  the  presence  of  calcium  in  the  nourishing 
liquid  is  absolutely  essential  for  the  continuance  of  the  cardiac  action,  not  only  in 
cold  but  also  in  warm-blooded  animals.  Binet  K  states  that  though  the  cardiac  ar- 
rest usually  takes  place  in  systole  in  calcium-salt  poisoning,  yet  if  the  salt  have 
come  directly  in  contact  with  the  heart  in  concentrated  form  there  is  paralytic  ar- 
rest (diastolic).  Further,  according  to  Ringer36  and  to  H.  G.  Beyer,"  the  volun- 
tary and  involuntary  muscles  of  the  frog  are  stimulated  by  small  amounts  of  cal- 
cium ;  and,  according  to  Franke,38  they  are  paralyzed  by  large  amounts  of  the 
drug.  Stefani w  states  that  calcium  chloride  when  applied  locally  in  minute  amount 
increases  the  functional  activity  of  the  motor  nerve-trunks,  but  when  in  large 
amount  produces  rapid  paralysis  ;  whilst  Binet  has  demonstrated  that  the  toxic 
dose  of  the  calcium  salt  directly  paralyzes  the  cerebral  cortex  and  the  motor  centres 
of  the  spinal  cord. 

It  is  certain  that  the  calcium  salts  are  essential  to  all  the  higher  tis- 
sues. It  is  probable  that  under  ordinary  circumstances  a  sufficiency  of 
these  salts  is  furnished  to  the  system  by  the  food,  and  that  no  gain  is  to 
be  achieved  by  their  further  administration.  This  is,  however,  only  a 
probability,  not  a  definitely  demonstrated  fact ;  it  may  be  that  the  soluble 
haloid  salts  have  more  practical  value  than  is  at  present  believed. 

LIQUOR  CALCII  OXIDI.  U.  S. — Solution  of  Lime. — Lime-water  \s  a 
colorless  liquid,  having  the  sp.  gr.  1.0015,  and  containing  about  0.15  per 
cent,  of  lime.  It  has  an  alkaline  taste,  and  is  nearly  destitute  of  irritant 
properties.  On  exposure  to  the  air  it  absorbs  carbonic  acid  and  deposits 
calcium  carbonate.  Twenty  minims  of  syrup  of  lime  (SYRUPUS  CALCIS, 
U.  S. )  equal  a  fluidounce  of  lime-water. 

THERAPEUTICS. — Lime-water  is  used  exclusively  as  a  local  remedy. 
In  vomiting,  from  almost  any  cause  except  acute  gastritis,  equal  parts  of 
lime-water  and  milk  afford  an  elegant,  simple,  and  much-used  remedy. 
If  the  vomiting  be  severe,  all  other  food  should  be  inhibited,  and  one  or 
two  tablespoonfuls  of  the  mixture  given  every  half- hour, — the  quantity, 
as  well  as  the  proportion  of  milk,  being  increased  as  the  stomach  is  able 
to  bear  it.  As  lime-water  when  put  in  milk  prevents  the  formation  of 
dense  coagula,  it  is  often  added  with  advantage  to  that  fluid  when  used 
as  food  for  infants,  or  for  adults  with  weak  digestion.  As  an  alkaline 
astringent,  the  syrup  is  often  useful  in  diarrhoea  in  doses  of  one  to  two 
fluidrachms  (4-7  C.c. ),  well  diluted. 

Externally,  lime-water  has  been  used  as  a  wash  in  various  skin  dis- 
eases, especially  in  tinea  capitis :  it  is  also  applied  to  ulcers,  and  is  said 
to  have  a  very  marked  influence  in  lessening  the  amount  of  discharge. 
When  mixed  with  an  equal  bulk  of  linseed  or  olive  oil  (LINIMENTUM 
CALCIS,  U.  S. ),  lime-water  forms  a  thick,  soapy  liquid  (Carron  Oil,  so 
called  from  the  name  of  the  iron-works  at  which  its  reputation  was  first 
made),  which  is  much  used  in  recent  burns. 

Lime-water  has  the  power  of  dissolving  mucus  and  also  false  mem- 
brane, and  has  therefore  been  introduced  as  a  local  remedy  in  pseudo- 


ANTACIDS.  803 

membranous  croup  and  in  diphtheria.  It  is  sometimes  used  by  causing 
the  patient  to  inhale  the  vapors  of  slaking  lime,  but  a  better  method  is 
to  pulverize  lime-water  by  means  of  an  atomizer  and  direct  the  spray 
upon  the  back  of  the  fauces  while  the  patient  is  respiring  deeply.  The 
application  should  be  made  every  two  or  three  hours. 

CALCIUM    CARBONATE. 

Chalk  is  the  native,  friable  calcium  carbonate,  a  milk-white,  soft 
solid,  of  an  insipid,  earthy  taste,  insoluble  in  water,  wholly  soluble,  with 
effervescence,  in  dilute  muriatic  acid.  CRETA  PR^EPARATA.  U.  S. — 
Prepared  Chalk  is  chalk  freed  from  impurities  by  pulverization,  leviga- 
tion,  and  elutriation  ;  a  white,  perfectly  smooth  powder.  CALCII  CAR- 
BONAS  PR^ECIPITATUS.  U.  S. — Precipitated  Calcium  Carbonate  is  a  white 
powder,  free  from  grittiness,  which  is  made  by  precipitating  calcium 
chloride  with  sodium  carbonate.  Dose  of  either  preparation,  twenty 
grains  to  a  drachm  (1.3-4  Gm. ). 

THERAPEUTICS. — Calcium  carbonate  in  its  different  forms  is  used  in- 
ternally as  an  antacid  and  a  very  mild  astringent.  As  none  of  the  salt? 
which  it  forms  are  purgative,  it,  with  the  other  preparations  of  lime,  is 
the  best  antacid  when  diarrhoea  is  present.  The  crude  chalk  should 
never  be  used,  but  the  other  preparations  are  probably  of  equal  value. 

Some  practitioners  assert,  however,  that  the  oyster-shell  is  more  acceptable  to 
delicate  stomachs,  on  account  of  the  animal  matter  which  it  contains  ;  and,  under 
the  name  of  Castilloes  Powder,  a  mixture  of  salep,  tragacanth,  sago,  of  each  three 
parts,  prepared  oyster-shell  one  part,  and  cochineal  sufficient  to  color  it,  has  been 
much  used  in  obstinate  summer  diarrhoeas.  A  drachm  of  this  is  boiled  in  a  pint  of 
milk,  and  the  decoction  taken  as  food  ad  libitum. 

Chalk  Mixture  (MISTURA  CRET^E,  U.S.)  contains  thirty  grains  of 
chalk  to  the  ounce  ;  dose,  one  to  two  tablespoonfuls  (15-30  Gm. ).  It 
is  often  combined  with  laudanum  or  paregoric  and  tincture  of  kino  or 
catechu. 

Externally,  prepared  chalk  and  precipitated  calcium  carbonate  are 
used  as  desiccants  and  protective  applications  to  idcers  and  chronic  burns, 
also  in  excessive  sweating  of  the  feet,  and  in  intertrigo  and  other  affec- 
tions of  the  skin. 

CALCII  SULPHAS  EXSICCATUS.  U.  S. — Dried  calcium  sulphate,  cr 
plaster  of  Paris,  is  never  used  in  medicine  save  for  mechanical  purposes  in 
the  making  of  plaster  bandages,  splints,  etc. 

CALCII  CHLORIDUM.  U.  S — Calcium  Chloride  is  locally  a  violent  irri- 
tant, but  it  is  strongly  recommended  by  S6e  in  the  treatment  of  gastric 
catarrh  and  fermentative  dyspepsia.  The  results  of  experimental  studies 
as  to  the  action  of  calcium  chloride  upon  the  heart  suggest  the  probability 
that  when  hypodermoclysis  is  indicated  in  conditions  involving  also  car- 


804 


EXTRANEOUS    REMEDIES. 


diac  failure,  the  addition  of  chloride  of  calcium  to  the  normal  saline  so- 
lution might  be  of  great  service.  J.  Bruce  MacCallum  (confirmed  by 
Ott)  has  found  that  calcium  chloride  very  markedly  inhibits  peristalsis  in 
the  rabbit,  and  suggests  its  use  in  nervous  diarrhoea.  Dose,  fifteen  to 
seventy -grains  a  day  (1-5  Gm). 

CALCIUM  IODIDUM. — Calcium  iodide,  containing  eighty  per  cent,  of 
iodine,  has  been  strongly  recommended  by  Germain  S£e  as  superior  to 
the  ordinary  iodides  and  less  apt  to  derange  digestion. 


REFERENCES. 


ANTACIDS. 


1.  CHAMBERS  .   .   .   .  The  Indigestions,  Am.  ed., 

1870,  67. 

2.  RABUTEAU  ....  L'Union    Med.,    1871,   xii. 

186. 

3.  GRANDEAU     .  .   .  J.  de  I'A.  P.,  1864. 

4.  GUTTMANN      .    .     .  V.  A.  P.  A.,  XXXV. 

5.  CURCI L.  M.  R.,  Oct.  15,  1886. 

6.  BEYER M.  News,  Sept.  4,  1886. 

7.  MAYET C.  R.  S.  B.,  1897,  ios.,  iv. 

8.  PODOCAEPOW    .   .  V.  A.  P.  A.,  xxxiii.  507. 

9.  SCHONLEIN    .   .   .  A.  G.  P.,  xviii. 

10.  RINGER  and  SAINSBURY  .  L.  L.,  1882,  ii.  736. 

11.  LAFFOUT    .  .  .   .  C.  R.  S.  B.,  1880,  282. 

12.  MILLS Canada  Med.  Surg.  Journ., 

March.  1886. 

13.  MUNCH Arch.  d.  Vereins  f.  Gemein. 

Arbeit.,  1863,  vi.  369. 

14.  DAMOURETTE  and  HYADES  .  J.  de  Th.,  1880, 

440. 

15.  MAYER Z.  K.  M.,  1881,  82. 

16.  OTT H.  S.  Jb.,  1883,  220. 


17.  CI.AR C.  M  W..  1888,  xxiv. 

18.  KLKMPTNER  .  .   .  Thesis,  Dorpat,  1889. 

19.  ROBERTS     ....  Urinary   and    Renal    Dis- 

eases, Am.  ed.,  1866,  240. 

20.  GLASS A.  E.  P.  P.,  1892,  xxx. 

31.  STOKVIS A.  E.  P.  P.,  xxi. 

22.  LEVI Centralbl.  f.  Allg.  Path.  u. 

Path.  Anal.,  1895,  vi. 

23.  HOVVELL  and  COOKE  .  J.  P.,  1893,  xiv. 

24.  RINGER J.  P.,v.,  vii. 

25.  BINET R.  M.  S.  R.,  1892. 

26.  RINGER N.  Y.  M.  R.,  xxxi. 

27.  BEYER M.  News,  Sept.  1886. 

28.  FRANKE Thesis,  Wiirzburg,  1889. 

29.  STEFANI A.  I.  B.,  1894,  xxii. 

30.  HOWBLL Contrib.    Med.    Research, 

Vaughan. 

31.  DALEBE  and  CARTERET  .  B.  G.  T.,  Nov.  1901. 

32.  LANGENDORFF  and  HUHCK  .  A.  G.  P.,  1903, 

xcvi. 

33.  OTT Ott's     Contributions     to 

Physiology,  part  16, 1905. 


FAMILY   II.— ANTHELMINTICS. 


THESE  are  medicines  which  kill  or  cause  the  expulsion  of  intestinal 
worms.  They  are  sometimes  divided  into  vermicides,  those  which  kill, 
and  vermifuges,  those  which  expel ;  but  there  is  little  or  no  practical  use 
in  the  division.  It  is  of  much  greater  importance  to  establish  the  rela- 
tions between  these  drugs  and  the  different  species  of  entozoa,  since 
clinical  experience  has  demonstrated  that  an  anthelmintic  very  efficient 
against  one  form  of  intestinal  worm  may  be  not  injurious  to  another 
species.  Therapeutically  considered,  the  entozoa  may  be  divided  into 
the  Tapeworms  (T&m&},  the  Round-worms  (Lumt>rzct\  and  the  Seat- 
worms  {Ascarides}.  The  last  of  these  differ  from  the  others  in  that  they 
are  to  be  attacked  solely  by  enemata. 

It  is  obvious  that  the  value  of  an  anthelmintic  depends  not  only  upon 
its  power  of  poisoning  the  articulate,  but  also  upon  its  harmlessness  as 
regards  the  patient.  Thus,  it  is  the  eminent  combination  of  these  quali- 
ties that  renders  the  infusion  of  quassia  so  valuable  in  cases  of  seat-worms, 
while  carbolic  acid,  though  very  efficient,  should  never  be  used  against 
the  same  parasite,  since  it  has  greatly  imperilled,  if  it  has  not  destroyed, 
the  life  of  the  patient  when  so  employed. 

There  are  certain  general  rules  which  govern  the  administration  of 
anthelmintics,  and  which  should  not  be  lost  sight  of.  They  may  be 
summed  up  as  follows  : 

Let  the  alimentary  canal  be  as  empty  as  possible,  so  that  the  drug 
may  act  with  the  greatest  force  upon  the  enemy.  For  this  reason, 
anthelmintics  are  best  administered  early  in  the  morning  ;  and  in  ob- 
stinate cases  the  patient  should  be  required  to  fast  until  dinner-time.  If 
the  drug  be  not  itself  a  purgative,  from  four  to  eight  hours  after  its  ad- 
ministration a  brisk  cathartic  should  be  given  ;  or  a  purgative  dose  of 
calomel  may  be  combined  with  it,  as  the  bilious  purging  induced  by  the 
latter  drug  seems  to  be  especially  obnoxious  to  the  entozoa. 

SPIGELIA— PINKROOT.     U.S. 

The  root  of  Spigelia  Marilandica,  an  herbaceous  perennial,  growing 
in  the  Southern  and  Southwestern  United  States.  It  consists  of  a  knotty 
head,  with  numerous  fine,  crooked,  branching  rootlets.  The  odor  is 
faint  and  peculiar  ;  the  taste  sweetish  and  slightly  bitter.  W.  L.  Dudley 

805 


806  EXTRANEOUS    REMEDIES. 

separated  from  it  an  alkaloid,  spigeline,  which,  according  to  Boorsma,1  is 
actively  poisonous. 

PHYSIOLOGICAL  ACTION. — Full  therapeutic  doses  of  spigelia  produce 
in  man  no  symptoms,  but,  according  to  Hodge  Thompson  (quoted  by 
Eberle),  Eberle,2  and  Spalsberg,s  an  overdose  causes  acceleration  of  the 
pulse,  dilatation  of  the  pupils,  heat  and  dryness  of  the  skin,  flushing  and 
a  swollen  appearance  of  the  face,  with,  in  Eberle' s  cases,  talkative  de- 
lirium. Two  fatal  cases  *  of  poisoning  by  it  are  said  to  have  been  re- 
corded. According  to  H.  A.  Hare,*  toxic  doses  slow  the  pulse  and 
depress  the  heart,  the  respiratory  centre,  and  the  motor  spinal  cord. 

In  Hare's  experiments  toxic  doses  of  spigelia  caused  in  the  dog  hurried  re- 
spiratory movements,  retching,  wide  dilatation  of  the  pupil,  internal  strabismus, 
marked  exophthalmia,  muscular  weakness  and  loss  of  coordination,  and  at  last 
sleep,  passing  into  coma  and  death  from  failure  of  respiration  ;  in  the  frog  exoph- 
thalmia, excessive  muscular  weakness,  loss  of  reflex  activity,  and  slowing  of  the 
heart,  with  at  first  increase  of  power  of  the  systolic  contractions  but  afterwards 
arrest  in  a  condition  of  semi-diastole. 

THERAPEUTICS. — Spigelia  is  a  most  efficient  remedy  in  cases  of  the 
round-worm,  and  is,  when  given  within  the  bounds  of  moderation,  entirely 
safe.  It  appears  to  narcotize  the  worm,  and  requires  the  use  of  a  brisk 
cathartic.  The  fluid  extract  (FLUIDEXTRACTUM  SPIGELIA,  U.  S. ) 
is  efficient  in  doses  of  two  fluidrachms  (7  C.c. ).  A  better  preparation  is 
the  Fluid  Extract  of  Spigelia  and  Senna  (£XTRACTUM  SPIGELIA  ET 
SENN^E  FLUIDUM,  U.  S.  1870),  which  is  much  liked  by  children  on 
account  of  its  agreeable  taste.  The  dose  for  an  adult  is  one-half  a  fluid- 
ounce  (15  C.c. );  for  a  child  two  years  old,  one-half  to  one  fluidrachm 
(2-4  C.c. ),  repeated  every  four  hours  until  it  purges. 

AZEDARACH,  the  bark  of  the  root  of  Melia  Azedarach,  or  Pride  of 
China,  is  used  in  the  South  as  a  remedy  for  the  round-worm.  It  is  said 
to  possess  poisonous  properties  similar  to  those  of  spigelia,  yet  it  is 
affirmed  that  animals  and  children  eat  its  fruit  with  impunity.  It  is  usu- 
ally given  in  decoction  (two  ounces  to  one  and  a  half  pints,  boiled  to  a 
pint),  the  dose  being  for  a  child  a  tablespoonful  (15  C.c)  every  two  or 
three  hours  until  the  bowels  are  affected. 

CHENOPODIUM,  or  Wormseed,  is  the  fruit  of  Chenopodium  anthel- 
minticum,  or  Jerusalem  Oak,  a  rank,  odorous  plant,  growing  about 
waste  places  in  the  suburbs  of  towns  in  the  United  States.  It  consists 
of  minute,  globular,  light  brown  seeds  about  the  size  of  a  pin's  head, 
of  a  nauseous  odor  and  a  pungent  taste,  due  to  the  volatile  oil  which 

*  These  cases  appear  to  have  been  indefinitely  copied,  and  are  of  doubtful  authen- 
ticity. 


ANTHELMINTICS.  807 

they  contain  in  large  quantity.  Wormseed  Oil  (OLEUM  CHENOPODII, 
U.  S. )  is  of  a  light  yellow  color,  becoming  darker  and  less  fluid  by  age, 
of  a  peculiar  powerful  odor  and  a  hot  burning  taste.*  It  has  been  used 
in  hysteria,  but  is  now  employed  only  as  an  anthelmintic  against  the  lum- 
bricus,  and  more  rarely  the  tapeworm.  It  is  very  efficient,  and  ten  drops 
(0.6  C.c. )  of  it  on  sugar  may  be  given  to  a  child  three  years  old,  before 
breakfast,  dinner,  and  supper,  for  two  days,  followed  by  a  brisk  purge. 

Cusso,  U.  S.,  Kousso,  Brayera,  is  the  female  inflorescence  of  Ha- 
genia  abyssinica,  a  tree  of  Abyssinia.  It  occurs  in  compressed  greenish- 
yellow  clusters,  of  a  fragrant  balsamic  odor,  and  a  taste  which  in  a  little 
while  becomes  acrid  and  disagreeable. 

The  crystalline  resin  Kosin,  discovered  by  Pavesi,  is  believed  by  Bedall5  to  be 
the  active  principle  of  kousso.  Leichsenring  affirms  it  to  be  Kosotoxin,  an  amor- 
phous, yellowish-white  substance,  which,  according  to  Handmann,  is  an  active 
paralyzant  to  all  muscles,  including  the  heart,  and  also  of  the  motor  nerv e-endings. 

Brayera  is  a  most  efficient  remedy  against  the  tapeworm,  and  even  in 
large  doses  causes  no  greater  inconvenience  to  the  patient  than  some 
nausea,  abdominal  pain,  and  looseness  of  the  bowels.  It  is  generally  not 
necessary  to  administer  any  purgative  with  it,  and  the  worm  is  discharged 
dead  with  the  last  watery  passages.  A  half-ounce  of  the  powdered  flow- 
ers is  given  suspended  in  water  in  the  morning,  with  the  usual  precau- 
tions as  to  diet.  The  best  preparation  is  the  yellowish-brown,  impure, 
amorphous  kosin  of  commerce,  which  may  be  given  in  doses  of  seven  to 
fifteen  grains  (0.5—1  Gm. )  repeated  every  half-hour  until  four  doses  have 
been  taken,  a  full  dose  of  castor  oil  being  administered  one  hour  later. 
Care  should  be  exercised  in  giving  bray  era  to  pregnant  women,  as  it  is 
stated  that  it  has  produced  abortion. 

SANTONICA— SANTONICA.     U.S. 

Levant  Wormseed  consists  of  the  unexpanded  flowers  and  peduncles 
of  Artemisia  pauciflora,  a  composite  of  Northern  Middle  Europe  and 
Asia.  It  consists  of  pale,  greenish-brown,  smooth  heads  of  four  or  five 
tubular  flowers  of  a  very  strong  aromatic  odor  when  rubbed,  and  a  bitter, 
disagreeable  taste.  It  contains  volatile  oil,  resinous  matter,  and  a  crys- 
talline principle,  Santonin  (SANTONINUM,  U.  S. ),  or  Santoninic  Acid, 
which  occurs  in  colorless,  pearly,  four-sided,  orthorhombic,  very  insoluble 

*  In  the  Maryland  Med.  Journ.,  iv.  20,  T.  R.  Brown  reports  a  case  in  which  death 
was  attributed  to  the  taking  of  an  ounce  or  more  of  wormseed  oil  in  divided  doses.  The 
patient  was  found  in  bed  unconscious,  with  vomited  matters  over  his  surroundings,  after 
some  hours  became  sensible,  relapsed  an  hour  or  two  later  into  heavy  sleep,  was  again 
roused,  and  while  playing  cards  became  aphasic,  deaf  to  conversation,  acutely  sensitive 
to  other  sounds,  and  finally  died  of  hemiplegic  apoplexy.  It  is  plain  that  the  worm- 
seed  was  not  the  direct  immediate  cause  of  all  these  symptoms  or  of  the  fatal  result. 


8oS  EXTRANEOUS    REMEDIES. 

tables.  It  has  a  neutral  reaction,  but  unites  with  alkalies  to  form  salts, 
and  hence  is  freely  soluble  in  alkaline  solutions. 

PHYSIOLOGICAL  ACTION. — Absorption  and  Elimination. — Santonin  is 
only  feebly  irritant.  It  is  absorbed  readily,  probably  as  a  sodium  santo- 
ninate,  and  by  its  elimination  produces  a  very  pronounced  reddish  discol- 
oration of  the  urine,  which  is  characteristic  of  the  poisoning. 

According  to  the  researches  of  Jaffe,85  santonin  is  eliminated  as  a 
new  substance — santogcnin,  and  also  as  a  derivative  of  santogenin — 
B-oxy  santonin. 

The  color  of  the  urine  is  a  very  marked  yellow,  which  has  at  first  an  orange 
tint,  but  after  very  large  doses  becomes  saffron-like,  or  sometimes  even  a  purplish 
red,  which  has  given  origin  to  the  idea  that  blood  was  present  in  it.  According  to 
Manns,'  the  addition  of  an  alkali  to  the  yellow  urine  causes  it  to  become  red. 

The  exact  form  in  which  santonin  is  thrown  off  is  not  established,  but 
probably  it  undergoes  oxidation  in  the  system.  Kletzinsky  asserts  that 
the  drug  receives  in  the  system  six  atoms  of  oxygen.* 

General  Effects. — The  first  and  most  characteristic  symptom  produced 
by  large  doses  of  santonin,  xanthopsia,  or  yellow  vision,  is  probably  due 
to  a  direct  action  of  the  poison  upon  the  retina. 

Xanthopsia  was  first  noticed  by  Calloud.  Usually  it  consists  of  a  very  deep 
yellow  tint  imparted  to  the  landscape  and  to  every  object  looked  at, — an  effect 
perhaps  most  comparable  to  that  of  looking  through  yellow  glass  ;  sometimes  this 
yellow  is  replaced  by  green  ;  and  Heydloff  states  that  he  has  seen  patients  in  whom 
the  tint  was  red,  and  others  in  whom  it  was  blue.  As  was  first  pointed  out  by 
Knies,"  the  period  of  yellow  vision  is  usually  preceded  by  one  of  violet  vision,  and 
during  the  stage  of  yellow  vision  there  is  a  lessening  or  complete  destruction  of  the 
sensibility  towards  the  violet  end  of  the  spectrum.  Two  theories  have  been  ad- 
vanced as  to  the  cause  of  the  yellow  vision  ;  first,  that  it  is  simply  due  to  staining 
of  the  humors  of  the  eye,  but  Rose 7  was  unable  to  find  any  dyestuff  in  any  portion 
of  the  body  except  in  the  medulla  of  the  kidney ;  and  Filehne,34  in  a  very  large 
series  of  studies  upon  human  beings  and  lower  animals  was  unable  to  find  any  staining 
either  of  the  humors  or  of  the  retina  itself.  Moreover,  the  theory  of  staining  does 
not  satisfactorily  account  for  the  violet  vision  which  precedes  the  yellow,  nor  for 
the  later  failure  of  the  power  of  recognizing  violet.  The  second  theory,  that  the 
disturbance  of  vision  is  due  to  the  action  of  the  drug  upon  the  retinal  elements 
themselves,  would  seem  to  be  strengthened  by  the  statement  of  Filehne  that 
changes  in  the  visual  purple  can  be  demonstrated  in  animals  fatally  poisoned  with 
santonin.  The  accuracy  of  this  statement  is,  however,  denied  by  Knies,  who  af- 
firms that  santonin  has  no  influence  upon  the  visual  purple  or  the  function  of  the 
rods  of  the  retina,  so  that  the  matter  would  seem  to  be  still  sub  judice. 

In  poisoning  by  santonin  great  pallor  of  surface,  with  a  blue  color 
around  the  eyes  or  involving  the  whole  countenance,  has  been  gen- 

*  Chrysophanic  acid  produces  a  discoloration  of  the  urine  similar  to  that  caused  by 
santonin.  According  to  Hoppe-Seyler,  the  cause  of  the  coloration  can  readily  be  distin- 
guished by  adding  caustic  soda  to  the  urine,  and  then  shaking  up  with  amylic  alcohol, 
when,  if  the  coloration  proceeds  from  santonin,  the  urine  is  decolorized,  while,  if  it  be 
due  to  chrysophanic  acid,  the  alcohol  takes  up  only  traces  of  the  coloring  matter. 


ANTHELMINTICS.  809 

erally  an  early  symptom  ;  vomiting  has  not  rarely  been  present,  and 
sometimes  has  been  accompanied  by  colicky  pains.  Besides  these  mani- 
festations, giddiness,  mental  apathy  or  stupor,  great  coldness  of  the 
surface,  profuse  sweating,  trembling,  mydriasis,  and  finally  loss  of  con- 
sciousness, with  convulsions,  often  violent  and  accompanied  by  opis- 
thotonos  and  emprosthotonos,  and  failure  of  respiration,  are  the  usual 
phenomena  of  santonin-poisoning.  The  circulation  seems  to  be  very 
little  affected.* 

According  to  Frohner,  moderate  doses  of  santonin  produce  in  domestic  animals 
polyuria,  sometimes  strangury,  and  very  commonly  so  pronounced  sexual  excite- 
ment as  to  suggest  that  the  drug  may  have  value  as  an  aphrodisiac.  The  toxic 
dose  causes  in  dogs  and  other  domestic  animals  accelerated  breathing,  slowing  of 
the  pulse,  universal  trembling,  cramps,  free  salivation,  unconsciousness,  convul- 
sions, dilated  pupils,  and  death,  f.  After  death  the  lesions  are  not  absolutely  con- 
stant, but  hyperaemia  of  the  nerve-centres  and  congestion  of  the  lungs  and  heart 
are  nearly  always  present. 

Santonin  must  have  a  powerful  action  upon  the  nervous  system,  but 
we  have  no  detailed  knowledge  as  to  its  general  physiological  action. 
Santonin  often  increases  the  flow  of  urine,  and,  according  to  Farquharson,* 
it  also  increases  slightly  the  elimination  of  urea. 

THERAPEUTICS. — Santonin  was  introduced  into  therapeutic  use  in 
1830  almost  simultaneously  by  Alms  and  by  Kahler,  and  is  one  of  the 
most  reliable  remedies  that  we  have  in  the  treatment  of  the  lumbricoid 
or  round-worm.  Von  Schroder 9  believes  that  he  has  proved  by  direct 
experiment  that  santonin  is  feebly  toxic  to  the  round-worm  ;  but  in  this 
he  is  in  opposition  to  the  general  clinical  experience  and  the  almost 
universal  belief  of  helminthologists  that  santonin  acts  directly  upon  the 
intestinal  parasite.  It  certainly  is  a  very  efficient  remedy,  but  it  should 
either  be  combined  with  or  followed  in  about  two  or  three  hours  by  a 
brisk  cathartic.  The  combination  of  calomel  and  santonin  has  been 
much  commended. 

As  long  ago  as  1862  Guepin  and  Martin10  recommended  santonin  in 
amaurosis,  asserting  it  to  be  especially  useful  in  those  cases  in  which 
there  had  been  choroiditis  and  iritis.  These  statements  have  been  con- 
firmed by  D.  Dyce  Brown,"  as  well  as  by  Ogston.  G.  Frank  Lydston 
affirms  that  santonin  is  a  valuable  remedy  in  epilepsy.  D.  H.  Bergey  " 
asserts  that  santonin  has  especial  relations  with  the  uterus,  and,  -if  given 
in  full  dose  at  the  time  of  the  molimen,  is  an  efficient  remedy  in  acute 
suppression  of  the  menses. 

TOXICOLOGY. — There  was  at  one  time  a  tendency  in  the  profession  to 
attribute  the  toxic  symptoms  caused  by  santonin  medicinally  given  to 

*  Case,  Arch,  fur  Exper.  Path,  und  Pharm.,  vi.  302. 

t  See  experiments  of  Manns  (Das  Santonin,  Marburg,  1851),  of  Rose  {Virchow's 
Archiv,  1859,  xvi.),  of  T.  Krauss  (Inaug.  Diss.,  Tubingen,  1869),  and  of  Frohner  (Monats- 
hefte  f.  Thierheilk.,  1893,  iv.). 


8io  EXTRANEOUS    REMEDIES. 

contaminating  strychnine.     The  incorrectness  of  this  has  been  demon- 
strated by  Krauss  and  others.      The  following  cases  are  instructive: 

A  child  five  years  old  was  killed  in  half  an  hour  by  an  unknown  quantity,"  and  one 
six  or  seven  years  old  is  said  to  have  been  destroyed  by  six  grains  of  the  acid,  after 
suffering  from  haematuria:14*  four  grains  produced  very  serious  symptoms  in  a 
child  four  years  old.15  In  Grimm's16  case,  a  rather  feeble  child  five  years  old  took 
two  one-grain  doses  of  santonin,  and  was  seized  with  convulsive  tremblings,  which 
increased  in  severity  until  they  became  severe  convulsions,  accompanied  by  uncon- 
sciousness, trismus,  pallor  of  the  face,  cold  sweats,  dilated  pupils,  and  rapid  pulse 
and  respiration.  Thirteen  or  fourteen  hours  after  the  ingestion  of  the  poison,  while 
the  patient  lay  on  her  back,  quiet,  unconscious,  with  moderately  dilated  pupils  and 
a  slow,  feeble  pulse,  death  occurred  suddenly.  Nine-tenths  of  a  grain  of  santonin 
are  said  to  have  caused  complete  unconsciousness  in  a  child  five  years  old."  Six 
grains  of  santonin  caused  in  a  child  five  years  old  epileptiform  convulsions  and 
death  in  thirty-five  minutes  (W.  J.  Kilner18).  One  grain  and  a  half  produced  in  a 
child  three  and  a  half  years  old  symptoms  of  the  utmost  severity,  not  reaching 
their  maximum  until  two  days  after  the  ingestion  of  the  poison  : 19  for  other  cases, 
see  C.  Bevill.20  In  one  case  complete  blindness  persisted  for  nearly  a  week. 

It  is  a  curious  fact  that  some  of  the  text-books  advise  the  use  of 
santonin  in  doses  larger  than  those  which  have  produced  serious  or 
even  fatal  poisoning.  Very  alarming  symptoms  have  been  occasioned 
by  two  one-grain  doses  exhibited  within  three  hours  in  a  child  eight 
years  old  (Grimm)  ;  in  a  child  two  and  a  half  years  old,  four  grains 
apparently  came  very  near  causing  death  (Berg21)  ;  and  in  the  fatal  case 
noted  on  page  792,  only  two  grains  were  taken  by  a  child  five  years  old. 
The  reason  large  doses  have  been  so  often  given  with  impunity  is  the 
great  insolubility  of  the  crystals  of  the  drug.  The  treatment  of  poison- 
ing by  santonin,  after  evacuation  of  the  stomach  and  bowels,  must  at 
present  be  entirely  tentative.  One  case  appears  to  have  been  saved  by 
artificial  respiration  ;  but  Binz 22  has  found  amyl  nitrite,  morphine,  and 
artificial  respiration  alike  useless  in  animals  :  chloral  given  before  the 
poison  appeared  to  be  of  service. 

ADMINISTRATION. — Santonin  is  best  administered  in  troches  (Tno- 
CHISCI  SANTONINI,  U.  S. )  each  one-half  a  grain,  so  that  the  slow  solu- 
tion of  the  santonin  in  the  intestine  shall  produce  the  greatest  possible 
effect  upon  the  worm  with  the  least  absorption  of  the  remedy.  The 
dose  for  an  adult  is  two  to  four  grains  (0.13-0.26  Gm. )  ;  for  a  child 
two  years  old,  one-quarter  to  one-half  a  grain  (0.016-0.03  Gm.).  For 
young  infants,  santonin  is  hardly  a  safe  remedy  in  any  efficient  dose. 
When  a  dose  of  any  size  is  given,  it  should  not  be  repeated  in  less  than 
eight  hours,  and  the  last  dose  should  be  accompanied  by  a  purgative 
amount  of  calomel. 

The  soluble  sodium  santoninate  is  much  more  dangerous  and  less 
efficient  than  santonin  :  the  object  is  to  get  as  much  of  the  remedy  as 

*  This  is  probably  a  mistaken  observation,  the  urine  being  only  blood-colored,  and 
not  containing  blood  (see  page  806). 


ANTHELMINTICS.  811 

possible  in  contact  with  the  worm,  and,  as  in  order  to  do  this  a  slow, 
not  a  rapid,  absorption  is  necessary,  the  insolubility  of  santonin  is  an 
advantage. 

ASPIDIUM.  U.  S. — Filix  Mas,  or  Male  Fern,  is^the  rhizome  of  Dryop- 
teris  filix  mas,  or  male  fern  of  Europe.  Under  the  name  of  Aspidium  * 
the  present  U.  S.  Pharmacopoeia  recognizes  both  it  and  the  rhizome  of 
the  indigenous  D.  marginale.  The  rhizome,  when  perfect,  is  from  six  to 
twelve  inches  long,  and  covered  with  large,  brown,  imbricated  scales. 
Its  taste  is  bitter  and  astringent. 

Aspidium  contains  an  amorphous  acid,  filicic, ^  which,  according  to  the  ex- 
periments of  E.  Poulsson,*3  is  a  very  active  substance,  causing,  in  the  frog,  at  first 
excitement  and  then  paralysis  of  the  central  nervous  system,  and  finally  paralyzing 
the  heart  and  exerting  a  marked  influence  upon  the  muscles  :  producing  in  warm- 
blooded animals  violent  diarrhoea,  with  a  general  paralysis  due  to  depression  of  the 
spinal-centres,  and  finally  cardiac  palsy.  Robert,2*  however,  as  the  result  of  his 
experiments,  believes  that  the  vermifuge  principles  of  male  fern  do  not  depend 
solely  or  even  chiefly  upon  filicic  acid,  but  upon  the  ethereal  oil. 

The  official  oleoresin  (OLEORESINA  ASPIDII,  U.  S. )  thoroughly  rep- 
resents the  crude  drug.  It  is  a  dark,  thick  liquid,  of  a  bitter,  nauseous, 
slightly  acrid  taste.  In  overdose  it  is  a  violent  poison,  producing  ex- 
cessive vomiting  and  purging,  with  general  weakness,  tremors,  cramps 
in  the  extremities,  increased  reflexes,  amaurosis,  and  finally,  in  some 
cases,  violent  tetanic  convulsions,  with  opisthotonos,  stupor  deepening 
into  coma,  and  collapse.  Icterus  is  sometimes  apparent.  Disturbance 
of  the  special  senses  is  a  not  infrequent  symptom  in  aspidium-poisoning. 
Deafness  without  loss  of  vision  has  been  noted  (case  of  Grant26). 
More  commonly  amblyopia  or  complete  amaurosis  occurs.  One  or  both 
eyes  may  be  affected,  and  total  blindness,  with  gray  atrophy,  may  remain 
as  a  permanent  condition  (Katayama  and  Okamoto  ;27  also  Bayer18). 
Experiments  upon  dogs  indicate  that  the  primary  influence  of  the  drug 
is  on  the  ganglion-cells  of  the  retina. 

The  icterus  of  aspidium  poison  has  been  attributed  to  the  inflammation  of  the 
duodenum,  but  Grawitz,  conceiving  that  it  might  be  of  haemic  origin,  found  on  ex- 
amination of  the  blood  of  patients  that  immediately  after  the  taking  of  large  doses 
of  the  extract  of  male  fern  there  was  a  marked  lessening  in  the  number  of  the  red 
blood-corpuscles.  Grawitz,  therefore,  came  to  the  conclusion  that  the  extract  is 
powerfully  destructive  to  the  red  blood-disks,  and  that  the  icterus  was  haemic  in  its 
etiology.  C.  Georgiewsky  has  found  that  in  rabbits  fatally  poisoned  with  male 

*  It  is  probable  that  many  species  of  the  genus  Aspidium  are  active.  Poulsson  (Arch, 
f.  Exper.  Path.  u.  Pharm.,  1895,  xxxv.)  separated  from  the  rhizome  of  Aspidium  spinulo- 
sum  two  acids  closely  allied  to  filicic  acid,  a  yellow  and  a  white  polystichic  acid  ;  and  both 
he  and  Valter  Laur6n  have  found  these  extracts  of  the  plant  to  be  active  taeniacides. 

t  Aspidin  of  R.  Boehm  (Archivf.  Exper.  Path.  u.  Pharm.,  1896,  xxxviii.)  is  distinct 
from  filicic  acid,  and  although  poisonous  both  to  frogs  and  to  higher  animals,  appears 
not  to  be  an  active  taeniacide. 


8i2  EXTRANEOUS    REMEDIES. 

fern  no  destruction  of  the  red  blood-corpuscles  occurs  if  death  takes  place  within 
twenty-four  hours  ;  but  that  if  the  symptoms  be  protracted  over  several  days  there 
is  a  very  distinct  lessening  in  the  amount  of  haemoglobin  in  the  blood  ;  and  that 
after  death  the  characteristic  change  of  the  poisoning  is  a  pronounced  wide-spread 
deposit  of  ferrous  pigments  in  the  liver,  the  spleen,  the  marrow  of  the  bones,  and 
sometimes  in  the  kidney^.  In  these  later  researches,  the  theory  of  Grawitz  that 
the  poison  acts  specially  upon  the  liver-cells  was  not  confirmed. 

After  fatal  poisoning  in  the  lower  animals  by  aspidium,  besides  the 
granular  pigmentation  just  spoken  of,  hemorrhagic  gastro-enteritis  and 
cystitis,  with  violent  parenchymatous  nephritis,  maybe  found  (Frohner  w). 
The  fatal  result  is  partially  due  to  violent  irritation  of  the  gastro-intes- 
tinal  tract  of  the  kidneys  ;  but  Ouirll  is  probably  correct  in  his  belief 
that  it  is  also  largely  the  outcome  of  the  influence  of  the  poison  upon  the 
nerve-centres,  to  which  factor  should  also  be  added  its  action  upon  the 
circulation.  The  minimum  fatal  dose  of  the  oleoresin  is  hardly  known, 
but  eight  grammes  of  the  extract  have  caused  death  in  a  child  about 
three  years  old  ;  six  drachms  of  the  oleoresin  have  several  times  proved 
fatal  in  the  adult:*  in  Paltauf's25  case  the  fatal  result  is  said  to  have  been 
due  to  four  and  a  half  grammes. 

THERAPEUTICS. — Male  fern  is  employed  almost  exclusively  against 
the  tapeworm.  In  its  administration  it  is  necessary  to  regard  strictly  the 
general  rules  applying  with  greater  or  less  force  to  all  anthelmintics,  but 
which  are  especially  imperative  when  a  drug  is  employed  against  the 
tapeworm.  The  patient  should  live  upon  milk  and  a  little  bread  for  one 
day,  and  the  following  morning  take  a  full  dose — one  half  to  one  flui- 
drachm  (2-4  C.c. ) — of  the  oleoresin,  fasting,  and  repeating  it  in  two  or 
three  hours.  At  noon  the  patient  may  eat  freely,  and  in  the  evening  a 
brisk  cathartic  should  be  given. 

PEPO.  U.  S. —  Pumpkin  Seed. —  The  seeds  of  the  ordinary  pump- 
kin are  a  most  valuable  remedy  in  cases  of  tapeworm,  perhaps  even 
more  efficient  than  the  male  fern,  and  perfectly  harmless.  Two  ounces 
(62  Gm. )  of  the  seeds  may  be  beaten  up  with  sugar  into  an  electuary, 
or  with  water  into  an  emulsion,  and  be  taken  fasting  in  the  morning,  the 
patient  having  dieted  the  previous  day.  Some  hours  after  their  adminis- 
tration a  brisk  purge  should  be  given.  I.  G.  Wolff  asserts  that  the 
active  principle  is  a  resin,  which  he  has  found  efficient  in  doses  of  fifteen 
grains  (i  Gm. ). 

TURPENTINE,  in  doses  of  half  a  fluidounce,  has  been  used  in  cases 
both  of  tapeworm  and  of  round-worm.  It  is  efficient,  but  is  liable  to 
produce  unpleasant  effects,  and  should  be  employed  only  when  other 
remedies  have  been  used  without  success  or  are  not  to  be  had.  It 

*  TTierap.  Monatsch.,  1889,  iii.  ;  Munchen.  Med.  Wochen.,  1890,  xxxvii.  ;  Lancet, 
1882;  Deutsch.  Med.  Wochen.,  1891,  xvii. 


ANTHELMINTICS.  813 

should  be  given   in  combination  with  twice  its  bulk  of  castor  oil,   or 
sometimes  in  smaller  doses  as  an  aid  to  other  vermifuges. 

GRANATUM.  U.  S. — Pomegranate  Rind. — The  bark  of  the  pome- 
granate root  is  efficient,  though  very  unpalatable,  against  the  tapeworm. 
The  decoction  of  the  fresh  root  (two  ounces  to  one  pint)  is  to  be  pre- 
ferred; a  pint  of  it  to  be  taken  in  three  doses,  an  hour  apart,  before 
breakfast.  The  dose  of  the  fluid  extract  (FLUIDEXTRACTUM  GRANATI, 
U.  S. )  is  thirty  minims  (2  C.c. ).  As  originally  stated  by  C.  Tanret," 
pomegranate  bark  contains  four  alkaloids;  the  most  important  are  pdle- 
tierine  (pumcine)  and  iso-pelletierine  (iso-punicine),  which  Dujardin- 
Beaumetz  has  shown  to  be  active  t&niacides.  In  the  higher  animals 
these  alkaloids  paralyze  the  peripheral  motor  nerves,  having  a  curare- 
like  action,  without  affecting  sensation  or  muscular  contractility.  G. 
Coronedi "  agrees  with  the  statement  that  the  paralysis  is  peripheral,  but 
believes  that  the  muscles  themselves  are  affected.  The  efficiency  of  pelle- 
tierine  as  an  anthelmintic  has  been  confirmed  by  various  clinicians.  A 
mixture  of  the  tannates  of  the  four  alkaloids  is  recognized  by  the  U.  S. 
Pharmacopoeia  as  PELLETIERIN^E  TANNAS,  U.  S. ,  and  may  be  used  in 
doses  of  four  grains  (0.3  Gm. )  as  a  tceniacide.  Dujardin-Beaumetz  also 
has  employed  it  successfully  in  Meniere'  s  disease,  and  states  that  hypo- 
dermic injections  of  six  grains  produce  in  man  severe  vertigo  and  mus- 
cular weakness,  with  great  retinal  congestion.  We  have  seen  five  grains 
cause  in  the  adult  pronounced  muscular  weakness  amounting  almost  to 
general  paralysis,  and  a  number  of  cases  have  been  reported  in  which  it 
has  produced  in  infants  symptoms  so  severe  as  to  discourage  its  employ- 
ment in  patients  of  that  class.*  Galezowski S2  has  used  pelletierine  in 
paralysis  of  the  third  and  sixth  pairs  of  nerves  with  asserted  good  results. 

THYMOL,  U.  S. ,  has  been  used  by  Neuma  Campi  f  for  the  destruction 
of  tapeworm  ;  he  gives  half  an  ounce  of  castor  oil  in  the  evening,  in  the 
morning  two  drachms  (7  Gm. )  of  thymol  divided  into  twelve  doses,  one 
to  be  taken  every  quarter  of  an  hour,  and  twenty  minutes  after  the  last 
dose  of  thymol  another  dose  of  castor  oil.  Thymol  is  a  specific  against 
hook-worms — the  Ankylostoma  {Uncinaria)  duodenale  and  the  A.  (U.) 
Americana.  After  starvation  for  twenty-four  hours,  a  thirty-grain  dose 
may  be  given  and  repeated  in  twenty-four  hours,  followed  by  a  brisk 
purge,  as  suggested  by  F.  M.  Sandwith.38  Giddiness,  fall  of  temperature 
from  one  to  two  degrees  C. ,  slowness  of  the  pulse  and  respiration,  stag- 
gering, and  even  collapse  are  liable  to  occur;  a  cure  is  almost  invariably 
effected  by  such  doses,  but  probably  smaller  amounts  would  suffice. 

K  AM  ALA. — Kamala. — The    glands   and    hairs    from    the   capsules 
of  Mallotus  philippinensis  are  used  against    the  tapeworm.       It   is   an 

*  See  Bull,  de  Therap.,  Ixxviii.,  Ixxix.,  Ixxx.,  cxi.,  July,  1886;  also  University  Med. 
Magazine,  \.  639. 

t  II  Raccoglitore  Medico,  abstracted  in  Buffalo  Med.  Journ.,  Oct.  1886. 


8i4  EXTRANEOUS    REMEDIES. 

orange-red,  very  inflammable,  granular  powder,  mixing  with  water  with 
some  difficulty,  and  containing  traces  of  a  volatile  oil  and  coloring 
resinoids,  to  one  of  which  Anderson  has  given  the  name  of  Rottlerin. 
Kamala  is  actively  purgative,  indeed  drastic,  and  may  cause  nausea  and 
vomiting.  A  tincture  of  it  may  be  used.  Dose  of  the  powder,  one  to 
two  drachms  (4-8  Gm. )  in  syrup,  given  in  the  morning,  and  repeated  in 
ten  hours  if  it  does  not  purge. 

ACIDUM  PICRUM. — Picric  or  carbazotic  acid,  on  account  of  its  corrosive  char- 
acter, is  used  internally  exclusively  in  the  form  of  the  ammonium  picrate,  which, 
according  to  Erb,*7  is  rapidly  absorbed  and  eliminated  in  the  urine,  and  produces, 
in  doses  of  fifteen  grains,  yellowness  of  the  conjunctiva,  skin  and  urine,  often 
accompanied  by  gastric  disturbances.  Von  Beck  K  reports  urticaria  and  measles- 
like  eruptions  produced  by  the  long  use  of  the  drug  ;  and  Achard  and  Clerc s9  have 
seen  violent  general  erythematous  swelling  of  the  limbs  produced  by  the  local  appli- 
cation of  the  solution  of  picric  acid. 

According  to  Binz,*°  picric  acid  acts  similarly  to  but  much  less  powerfully 
than  does  quinine  upon  infusoria.  W.  Erb  found  that  a  single  dose  of  eight  grains 
will  produce  in  the  rabbit  falling  temperature,  weakness,  diarrhoea,  collapse  ending 
in  death,  sometimes  preceded  by  convulsions.  The  blood  of  animals  slowly  killed 
by  the  picrate  was  a  dirty-brown  color,  with  distinct  nuclei  in  the  red  blood-disks 
and  floating  free  in  the  serum.  The  alterations  in  the  red  blood-corpuscles  occurred 
during  life,  and  could  be  produced  by  mixing  ammonium  picrate  with  blood  out- 
side of  the  body.  Ammonium  picrate  has  been  commended  as  an  antiperiodic,  but 
is  of  no  value;  nor  does  it  seem  useful  as  an  anthelmintic  or  in  trichiniasis.  (See 
Erb.)  Hammond41  declares  that  the  salts  of  picric  are  specific  in  exophthalmic 
goitre.  According  to  Erb,  the  ammonia  salt,  nine  to  twelve  grains  a  day,  may  be 
given  with  safety. 

REFERENCES. 

ANTHELMINTICS.  21.  BERG Wiirtemberg  Med.  Corres- 

pondenzbl.,  1862. 
i.  BOORSMA    ....  P.  J.  Tr.,  1898.  22    BINZ A.  E.  P.  P.,  vi.  300. 

2-  EBERLE Mat*na       .Medlca        and  23.  POULSSON  ....  A.  E.  P.  P.,  1891,  xxix. 

fherap  ,  i.  KOBERT Th.  M.,  1893. 

3.  SPALSBERG     .  .  .  fc  M  S.  J    1885.  25   PALTAUF s  Jb    ^^, 

«•  HARE M   News,  March  12, 1887.  26   GRANT S.  Jb.,  ccxlix. 

5-  BEDALL SydSoc.  Year-Book,  1868,  27.  YANAMATSU     and     OKAMOTO  .  Viertelj.     f. 

Gericht.     Med.    u.    Off. 

6-  MANNS ^    Santonin,    Marburg,  San ^  ^  viij    Supp, 

28.  BAYER Prag.      Med.      Wochens.. 

7-  ROSE V.  A.  P.  A.,  xvi.  233;  xvni.  l888  xjj 

15;    xix.    522;    xx.    245;       ^    FROHNER    .   .   .    .  Monats.       Prakt.     Thier- 

heilk.,  1890. 

8.  FARQUHARSON  . . .  B.  M.  J.,  1872.  TANRET  .  .  B.  G.  T.,  xcviii.  316. 

9.  VON  SCHRODER  .  A.  E.  P.  P.,  xix.  304.  CORONEDI  ....  La  Sperimentale,  1892. 
10.  GUEPIN    and    MARTIN  .  Ann.   de    Therap.,       ^    GALEZOVVSKI     .  .  B.  M.  J.,  Nov.  28,  1885. 

33.  SANDWITH  ....  Anchylostomiasis.  1894. 
ji.  BROWN    ...       .  Brit,  and  For.  Med.-Chir.       ^   FlLEHNE  .  A.  G.  P.,  1900,  Ixxx. 

35-  JAFFE P.  J.  Tr.,  1897.  lix. 

12'  BERGEY Amer-  Therap.,  July,  1892.         ^  KNIES A  of  Op    IgOQj  xxix 

P.  J.  Tr.,  vin.  996-  37.  ERB Die     Pikrinsaiire,     Wiirz- 

14.  B.  G.  T.,  Ixxiv.  362.  burg  I865 

38.  VON  BECK.   .   .  .  Charite-Annalen,     1892, 
16.  GRIMM     Schweizer  Zeitsch.  f.  Med.-  ^jj 

Chir.,  u.  Geb.,  1852,  493-         39.  ACHARD  and  CLERC  .  G.  H.  M.  C.,  1900,  xlvii. 

S.  Jb.,  cci.  128.  4<)    BlNZ V.  A.  P.  A.,  xlvi.  130. 

18.  KILNER St.  Thomas's  HosP.Rep.,x.       4,    HAMMOND  .   .   .   .  N.  Y.  M.  J.,  Jan.  1890. 

20.  BEVILL T.  G.,  iii.  428. 


FAMILY   III.— DIGESTANTS. 


IN  this  family  are  associated  a  few  remedies  which  are  used  to  aid  the 
alimentary  canal  in  dissolving  the  various  articles  of  food. 

PEPSIN. 

As  is  well  known,  there  is  secreted  by  the  gastric  glands  a  peculiar 
albuminous  body,  which  has  the  power  not  only  of  coagulating  albumin, 
but  also,  with  the  aid  of  acidulated  water,  of  redissolving  it.  To  this 
principle  the  name  of  pepsin  has  long  been  given.  A  discussion  of  its 
nature  and  properties  would  be  more  in  place  in  a  work  on  physiology 
than  in  one  on  therapeutics.  The  U.  S.  Pharmacopoeia  now  recognizes 
a  stronger  and  weaker  pepsin.  PEPSINUM,  U.  S. ,  or  Pepsin,  is  required 
by  the  Pharmacopoeia  to  be  able  to  digest  three  thousand  times  its  weight 
of  freshly  coagulated  egg  albumin.  The  U.  S.  Pharmacopoeia  of  1890 
recognized  a  Saccharated  Pepsin  containing  ninety  per  cent,  of  sugar  of 
milk. 

The  dried  stomach  of  calves  has  been  used  from  time  immemorial  for  the  pur- 
pose of  coagulating  milk,  by  housewives,  with  whom  it  is  customary  to  place  the 
dried  viscus  in  wine,  and  to  call  the  liquid  thus  formed,  as  well  as  the  prepared 
stomach,  rennet.  It  is  stated  by  James  Gray l  that  rennet-wine  should  be  of  such 
strength  that  one  teaspoonful  of  it  will  coagulate  a  pint  of  milk.  Rennet  is  said  to 
have  been  long  employed  in  England  as  a  domestic  remedy  in  dyspepsia.2  In 
South  America  the  inner  coat  of  the  gizzard  of  the  ostrich  is  stated  to  be  put  to  a 
similar  use  (E.  S.  Wayne8),  and  in  our  own  country  the  dried  gizzards  of  chickens 
and  turkeys  are  no  less  famous  among  medically  inclined  housewives. 

Various  processes  have  been  suggested  for  the  preparation  of  the 
drug,  but  none  of  them  yields  a  pure  proximate  principle,  if  indeed  pep- 
sin have  really  such  nature  and  be  not  an  albuminous  body  of  varying 
constitution. 

Whatever  form  of  pepsin  be  used,  if  good  effects  are  to  be  obtained 
from  it  it  must  be  given  with  acid,  unless  indeed  there  be  reason  to  be- 
lieve that  this  constituent  of  the  gastric  juice  is  not  wanting.  Alcohol 
destroys  the  digesting  power  of  pepsin,  and  therefore  wines  are  inferior 
preparations  of  it.  The  reactions  of  pepsin  with  organic  and  inorganic 
matters  are  very  complex,  and  not  well  understood  :  consequently  we 
think  the  physician  should  eschew  all  elixirs  or  compound  preparations 

815 


8i6  EXTRANEOUS    REMEDIES. 

of  the  drug,  using  only  the  powdered  pepsin  or  a  glycerole  of  pepsin,  or 
a  freshly  prepared  digestive  solution  of  water  and  muriatic  acid,  or  glyce- 
rin, water,  and  muriatic  acid.  If  other  remedies  are  to  be  given  it  is 
no  great  hardship  to  write  a  second  prescription  for  them. 

THERAPEUTICS. — It  is  a  question  of  some  importance  to  decide  how 
far  pepsin  is  valuable  and  reliable  as  a  medicine.  It  is  evident  that  any 
influence  for  good  which  it  possesses  is  dependent  upon  its  solvent 
power,  and  that  this,  therefore,  is  a  measure  of  its  value.  Only  a  small 
portion  of  commercial  pepsin  approximates  in  power  the  official  stand- 
ard. Moreover,  the  pepsin  in  life  must  soon  pass  out  of  the  stomach. 
One  of  two  conclusions  seems  to  be  inevitable  :  either  the  doses  of  pepsin 
habitually  used  are  preposterously  small  or  else  pepsin  acts  upon  the 
stomach  itself  in  some  way  as  a  stimulant.  Clinically,  pepsin  has  been 
used  with  asserted  advantage  in  the  /oss  of  digestive  power  in  adults, 
whether  primary  or  occurring  in  the  course  of  other  affections.  Proba- 
bly four-fifths  of  the  drug  which  has  been  given  has  been  inert,  either 
originally  or  from  the  method  of  its  administration  ;  and  in  the  great 
majority  of  cases  the  good  that  has  been  achieved  has  been  due,  not 
to  the  pepsin,  but  to  the  regulation  of  the  diet  and  habits  of  the  patient 
and  to  the  drugs  which  have  been  exhibited  along  with  the  animal  fer- 
ment. The  value  of  pepsin  has  been  overestimated,  and  it  has  been  given 
to  adults  in  ridiculously  small  doses  :  at  least  half  a  drachm  (2  Gm.) 
of  the  ordinary  commercial  article,  or  of  the  Saccharated  Pepsin,  U.  S. , 
should  be  exhibited  at  a  dose.  The  testimony  as  to  the  usefulness 
of  pepsin  in  diseases  of  young  children  is  very  strong.  To  such  it  is 
generally  given  in  doses  proportionately  much  larger  than  those  usually 
exhibited  to  adults.  The  use  of  small  doses  of  pepsin  in  children  is 
therefore  much  more  rational  than  in  adults  ;  and  our  own  experience 
is  in  close  accord  with  what  seems  to  us  the  dictates  of  common  sense  : 
in  the  chronic  indigestion  and  consequent  diarrhoea  of  young  children  it 
may  be  tried  with  great  hope  of  benefit.  To  a  baby  six  months  old  five 
grains  (0.3  Gm.)  of  the  saccharated  pepsin  may  be  given  in  a  little 
acidulated  water  after  each  feeding.  Pepsin  (U.S.)  given  in  doses 
of  ten  to  fifteen  grains  (0.7—1  Gm. )  to  the  adult  probably  has  some 
digestive  value. 

PANCREATIN,  U.  S.,  has  been  extensively  used  in  dyspepsia  as  a 
digestant  in  lieu  of  pepsin.  For  action  it  requires  the  presence  of  an 
alkali,  and  in  the  acid  gastric  juice  would  not  only  not  act,  but  would 
itself  in  all  probability  be  digested  and  destroyed  as  a  ferment ;  *  and  it 
is  of  no  value  except  for  the  preparation  of  predigested  foods. 

EXTRACTUM    MALTI. 

Malt  is  the  seeds  of  the  ordinary  barley  caused  to  enter  the  incipient 
stage  of  germination  by  artificial  means  and  dried.  It  is  prepared  by  soak- 
ing the  grains  in  water  and  leaving  them  in  heaps  in  a  room  of  moderate 


DIGEST  ANTS.  817 

temperature,  and  by  occasional  turning  preventing  the  heat  given  off 
during  the  process  of  germination  from  accumulating ;  then  finally  killing 
the  germ  with  heat.  The  color  varies  from  pale  amber  to  black,  according 
to  the  degree  of  the  heat  used  in  drying.  There  is  formed  during  germi- 
nation a  peculiar  ferment,  diastase,  one  part  of  which  is  able  to  convert 
about  two  thousand  parts  of  starch  into  dextrin  and  glucose.  The  Ex- 
TRACTUM  MALTI  of  the  U.  S.  Pharmacopoeia  is  made  by  rapidly  evapo- 
rating an  infusion  of  malt  to  the  consistency  of  a  thick,  honey -like  liquid 
at  a  temperature  not  above  130°  F.  It  should  contain  practically  all  the 
diastase  of  the  malt.  The  odor  of  the  extract  of  malt  is  slight  and  pecu- 
liar, the  taste  sweet,  and  the  reaction  to  paper  distinctly  acid.  It  dis- 
solves freely  in  water,  and  is  precipitated  by  alcohol,  tannic  acid,  mercuric 
chloride,  and  various  other  metallic  salts.  Commercial  malt  extracts 
vary  greatly  :  some  of  them  are  practically  preparations  of  glucose, 
others  are  of  the  nature  of  strong  or  weak  beers.  True  extract  of  malt 
contains  no  alcohol  at  all.  Extract  of  malt  has  been  much  used  in 
cases  of  disease  with  failing  nutrition,  and  especially  when  the  power  of 
digesting  substances  is  feeble.  When  it  contains  largely  either  glucose 
or  alcohol  it  affords  food -material  to  the  system  ;  but  the  important  ques- 
tion for  the  therapeutist  is,  How  far  is  it  possible  in  disease  to  aid  in  the 
digestion  of  starchy  substances  in  the  stomach  and  intestines  by  the  use 
of  diastase  ?  R.  H.  Chittenden  and  G.  W.  Cummins  have  made  a  series 
of  investigations  in  order  to  determine  the  conditions  which  are  necessary 
for  the  amylolytic  action  of  diastase.  They  find  that  it  acts  better  in  a 
neutral  than  in  an  alkaline  solution  ;  that  proteid  matters  when  present 
in  the  alkaline  solution  prevent  the  retarding  influence  of  an  alkaline 
carbonate  ;  that  neutral  peptone  exerts  a  direct  stimulant  effect  on  the 
amylolytic  action,  but  that  the  greatest  amylolytic  action  is  observed  in 
the  presence  of  proteid  matter  partially  saturated  with  acid,  although  a 
larger  percentage  of  acid-proteids  may  cause  complete  destruction  of  the 
ferment.  These  results  seem  to  prove  that  diastase,  when  taken  into  the 
stomach,  must  sooner  or  later  be  completely  destroyed  by  the  gastric 
juice,  and  that  in  order  for  it  to  have  any  distinct  effect  upon  digestion  it 
must  be  given  at  the  beginning  of  the  meal.  In  cancer  of  the  stomach 
and  other  diseases  in  which  the  gastric  juices  lack  acidity,  the  action  of 
diastase  upon  starch  must  be  more  pronounced  ;  but  unfortunately  the 
failure  of  the  starch-digestion  is  usually  associated  with  gastric  hyper- 
acidity. 

PAPAIN. 

The  Carica  Papaya  is  an  herbaceous  tree  universally  cultivated  in 
tropical  countries  for  its  fruit,  the  papaw,  the  juice  of  which  yields  a 
peculiar  ferment,  to  which  the  name  of  Papain  was  given  by  Wurtz, 
but  which  is  now  generally  known  by  the  name  originated  by  Pekolt, 
Papayotin.  This  substance  is  a  ferment,  which  has  the  power  of  dis- 
solving fibrin,  muscular  fibres,  tissues,  etc. 

52 


8l8  EXTRANEOUS    REMEDIES. 

According  to  \Vurtz,  one  part  of  papain  in  alkaline  solution  at  a  temperature 
of  40°  C.  is  capable  of  dissolving  one  hundred  and  seventy-five  parts  of  moist 
fibrin,  which  it  converts  into  a  peptone.  VVurtz  affirms  that  it  makes  no  differ- 
ence whether  the  solvent  solution  be  alkaline  or  acid,  but  Brunton,  Wyatt,  and 
Martin  state  that  as  little  as  one-half  per  cent,  of  hydrochloric  acid  arrests  the 
digestion.  Albrecht,  however,  reaffirms  that  hydrochloric  acid  hastens  the  action 
of  papain,  and  states  that  the  official  preparation  in  use  in  the  Paris  hospitals  is  an 
acid  one.  Further,  in  an  elaborate  series  of  experiments,  August  Hirschler 5  reaches 
the  result  that  digestion  goes  on  most  rapidly  in  acid  solutions,  that  it  is  very  feeble 
in  alkaline  solutions,  and  ceases  entirely  when  the  alkalinity  becomes  excessive.  It 
is  stated  that  in  order  to  convert  fibrin  entirely  into  pure  peptone,  so  that  nitric  acid 
will  produce  no  precipitate,  the  proportion  of  the  ferment  must  be  at  least  three  per 
cent.,  and  the  digestion  must  continue  for  forty-eight  hours. 

Papain  first  coagulates  milk,  then  precipitates  it,  and  finally  digests 
it  into  a  thin  fluid.  Taken  into  the  stomach,  papain  has  no  action  upon 
the  living  tissues,  but  one  grain  of  it  injected  directly  into  the  blood  is 
sufficient  to  cause  death  in  a  very  short  time  in  rabbits  or  in  dogs.  Its 
action  on  albuminoids  is  said  to  resemble  that  of  trypsin  rather  than  that 
of  pepsin.  (See  Martin.6) 

Papain  has  been  used  in  medicine  as  a  substitute  for  pepsin,  in  doses 
of  five  to  ten  grains  (0.3-0.6  Gm. ).  It  has  also  been  very  highly  recom- 
mended for  the  purpose  of  destroying  organic  tissues  of  low  type,  as  in 
diphtheria  (A.  Jacobi7),  in  the  thickening  of  chronic  eczema,  in  warts, 
and  in  pyogenic  membranes  surrounding  old  sinuses  or  abscesses.  It  is 
not  caustic,  but  simply  dissolves  the  diseased  tissues,  and  is  said  to  cause 
no  pain.8  It  should  be  applied,  one  part  each  of  papain,  glycerin,  and 
water.  In  our  laboratory  experiments  commercial  papain  of  the  most 
esteemed  brands  has  failed  to  exert  any  solvent  power  over  albuminous 
substances,  and  it  is  probably  a  remedy  of  little  value. 


REFERENCES. 

DIGESTANTS  5-  HlRSCHI-ER    •   •    •  Ungar.     Arch.     f.     Me.L, 

1893,  i. 

1.  GRAY Ed.  M.  J.,  Jan.  1853.  6.  MARTIN B.  M.  J.,  July  25,  1885. 

2.  M.  T.  G.,  April,  1857.  7.  JACOBI T.  G.,  ii. 

3.  WAYNE Amer.  Journ.  Pharm.,  1868.         8.  Birmingham    Med.    Rev., 

4.  N.  Y.  M.  R.,  xl.  398.  May.  1886. 


FAMILY   IV.— ABSORBENTS. 


THIS  class  contains  remedies  which  are  used  for  the  purpose  of 
absorbing  acrid  and  deleterious  materials,  such  as  offensive  discharges 
on  the  exterior  of  the  body,  and  acrid  secretions,  or  the  irritant  products 
of  the  partial  decomposition  of  food,  in  the  alimentary  canal.  For  the 
first  purpose  very  fine  dry  earth  and  plaster  of  Paris  are  used  to  some 
extent  in  practice  ;  but,  as  their  employment  is  purely  within  the  prov- 
ince of  the  surgeon,  we  shall  say  no  more  about  them  here. 

CHARCOAL. 
Charcoal  is  official  in  the  U.  S.  Pharmacopoeia  in  two  forms  : 

CARBO  LIGNI.  —  Charcoal  prepared  from  wood. 

CARBO  ANIMALIS. — Animal  Charcoal,  prepared  from  bone. 

Charcoal  for  medicinal  purposes  should  be  made  out  of  a  light,  porous 
wood  :  that  prepared  from  the  young  shoots  of  the  willow  or  of  the  pop- 
lar is  almost  exclusively  employed.  It  is  a  black,  brittle  substance,  and 
should  have  more  or  less  lustre.  It  has  a  very  remarkable  power  of  ab- 
sorbing many  times  its  own  bulk  of  gases,  and,  when  exposed  to  the  air, 
increases  rapidly  in  weight.  It  should  therefore,  when  intended  for 
medicinal  purposes,  be  powdered  as  soon  as  it  is  burnt,  and  put  in  small, 
completely  filled,  closely  sealed  bottles. 

Animal  charcoal,  or  bone-black,  formed  as  it  is  by  the  partial  burning 
of  bones,  contains  a  large  percentage  of  calcium  phosphate  and  carbon- 
ate. Purified  Animal  Charcoal  (CARBO  ANIMALIS  PURIFICATUS,  U.  S. ) 
is  prepared  by  removing  the  lime  salts  by  dilute  muriatic  acid. 

THERAPEUTICS. — Internally,  charcoal  is  employed  as  an  absorbent  in 
fermentative  intestinal  dyspepsia,  cardialgia,  and  similar  disorders.  As 
moist  charcoal  is  not  an  absorbent,  it  is  evident  that  it  is  of  very  little 
value  ;  its  habitual  employment  is  generally  combined  with  that  of  laxa- 
tives for  fear  of  accumulation  in  the  alimentary  canal.  Dose  of  charcoal 
from  one  to  two  drachms  (4-8  Gm. ).  Except  in  a  mechanical  way,  it 
is  perfectly  innocuous  in  any  dose. 


819 


FAMILY  V.— DISINFECTANTS. 


DISINFECTANTS  are  agents  which  are  used  for  the  purpose  of  pre- 
venting the  growth  of  bacteria.  This  may  be  accomplished  in  two  ways, 
— either  by  killing  the  germs  (germicides)  or  by  rendering  the  media  un- 
favorable for  the  growth  of  the  micro-organisms  (antiseptics).  All 
chemical  germicides  become,  however,  when  in  dilute  solution,  antiseptic, 
so  that  the  natural  division  of  these  agents,  as  given  above,  does  not 
serve  well  as  a  basis  of  a  classification  for  systematic  study.  Disinfectants 
may  be  conveniently  divided  into  forces,  and  material  chemical  groups  as 
follows  : 

I.   Forces ;  heat  and  cold. 

II.  Metallic  salts,  including  certain  salts  of  mercury,  silver,  copper, 
zinc,  and  iron. 

III.  Halogens,    including    chlorine   and    the    hypochlorites,    iodine, 
bromine,  and  their  various  compounds. 

IV.  Oxidizing  disinfectants,  including  especially  hydrogen  dioxide 
and  potassium  permanganate. 

V.  Carbon  compounds,  including  carbolic  acid,  cresylic  acid,  creosote, 
salicylic  acid,  benzoic  acid,  thymol,  menthol,  alcohol,  formaldehyde,  the 
volatile  oils  and  allied  drugs. 

VI.  Acids  and  alkalies,  including  especially  sulphurous  acid,  boric 
acid,  hydrofluoric  acid,  and  their  salts. 

I.— COLD   AND   HEAT. 

Cold. — The  effect  of  low  temperature  in  preventing  the  growth  of 
micro-organisms  is  well  known  and  daily  taken  advantage  of  by  the 
housewife  in  the  preservation  of  foodstuffs.  Very  few  bacteria  will  multi- 
ply at  a  temperature  lower  than  40°  F.  On  the  other  hand,  cold  cannot 
be  considered  as  a  germicidal  agent,  for  it  has  been  shown  that  even  the 
extraordinarily  low  temperature  of  liquid  air  does  not  destroy  the  vitality 
of  the  typhoid  bacillus  and  other  test  organisms. 

Heat. — As  a  germicide  fire  is  absolutely  efficient,  but  destructive. 
The  lower  degrees  of  heat  have  been  used  without  moisture  (dry  heat), 
and  with  moisture  (moist  heat). 

Moist  heat  is  much  more  efficient  than  is  dry  heat. 

According  to  Sternberg,  while  most  micro-organisms  are  destroyed  in  the 

presence  of  moisture  by  a  temperature  of  62°  C.  (143°  F. ),  certain  of  the  more 

resistant    species   of   bacteria    will   withstand  a   heat    considerably    higher    than 

this  ;  but  all   bacteria  free  from  spores  are  destroyed  by  the   heat  of   boiling 

820 


DISINFECTANTS.  821 

water  in  one  to  two  minutes.  On  the  other  hand,  some  spores  are  able  to  with- 
stand boiling  water  for  several  hours.  To  destroy  with  certainty  all  forms  of  life 
requires,  according  to  Steinberg,5  an  exposure  to  moist  heat  of  a  temperature  of 
115°  C.  (239°  F. )  for  half  an  hour.  This  temperature  can  of  course  be  produced 
only  under  pressure.  The  most  satisfactory  manner  of  using  this  method  of  ster- 
ilization is  by  means  of  the  autoclave,  an  apparatus  so  arranged  as  to  prevent  the 
escape  of  the  steam  until  the  pressure  within  the  autoclave  has  reached  nine  to 
ten  pounds,  at  which  time  the  temperature  will  approximate  115°  C. 

Dry  heat  is  much  inferior  in  its  germicidal  effect  to  moist  heat. 

Wolf1  found  that  dry  air  at  140°  C.  was  scarcely  more  destructive  than  its 
watery  vapor  at  100°;  Koch,  that  five  minutes'  exposure  to  steam  was  equal  to  an 
hour  or  an  hour  and  a  half  with  the  dried  air.  The  results  reached 'by  Koch  and 
Wolffhiigel*  are  in  accord  with  other  evidence,  and  may  be  considered  correct. 
They  are  as  follows  : 

1.  A  temperature  of  100°  C.  (212°  F.),  dry  heat,  maintained  for  one  hour  and 
a  half,  will  destroy  bacteria  which  do  not  contain  spores. 

2.  Spores  of  mould-fungi  require  for  their  destruction  in  hot  dry  air  a  tem- 
perature of  from  110°  to  115°  C.  (23o°-239°  F.)  maintained  for  one  hour  and  a 
half. 

3.  Bacillus-spores   require  for  their  destruction  in  hot  air  a  temperature  of 
140°  C.  (284°  F. )  maintained  for  three  hours. 

4.  In  dry  air  the  heat  penetrates  objects  so  slowly  that  packages,  such  as  pillows 
or  small  bundles  of  clothing,  are  not  disinfected  after  an  exposure  of  from  three  to 
four  hours  to  a  temperature  of  140°  C.  (284°  F. ). 

5.  Exposure  to  a  temperature  of  140°  C.  ( 284°  F. )  in  dry  air  for  a  period  of 
three  hours  injures  most  objects  requiring  disinfection  (clothing,  bedding,  etc.)  to 
a  greater  or  less  degree. 

George  H.  Roh£ 3  found  that  rolls  of  blankets  exposed  in  a  chamber  heated  to 
280°  F.  for  three  hours  were  very  slightly  affected  in  their  interior.  This  is  in 
strict  accord  with  the  teaching  of  Parsons  and  Klein,*  of  the  London  Local 
Governing  Board,  and  of  other  observers. 

Dry  heat  is  so  inferior  to  moist  heat  that  it  is  at  present  never  em- 
ployed as  a  germicide.  Quarantine  and  other  health  stations  are  or 
ought  to  be  supplied  with  apparatus  for  exposing  infected  articles  to  the 
prolonged  action  of  hot  steam  in  chambers,  etc.  For  ordinary  household 
purpose,  however,  the  physician  is  forced  to  rely  upon  boiling,  which, 
when  maintained  for  thirty  minutes,  may  be  considered  as  practically 
efficient. 

II.— METALLIC   SALTS. 

.  HYDRARGYRUM  CHLORIDUM  CORROSIVUM. — The  bichloride  of  mer- 
cury has  long  been  recognized  as  one  of  the  most  powerful  germicides 
known. 

In  1870  John  Dougall  announced  that  corrosive  sublimate,  i  part  in  6500,  would 
kill  spermatozoa,  and  i  part  in  6000  infusoria  ;  the  later  researches  of  Koch,  Jalan 
de  la  CroSx,  and  Sternberg  have  confirmed  this  result,  and  shown  that  corrosive 
sublimate  is  one  of  the  most  powerful  of  known  germicides.  Micrococci  and  bacilli 
in  active  growth  without  spores  are  killed  by  solutions  of  i  in  20,000,  while  solutions 


822  EXTRANEOUS    REMEDIES. 

of  i  in  1000  will  rapidly  destroy  the  spores  of  B.  anthracis  and  B.  subtilis.  Results 
contrary  to  these  have,  it  is  true,  been  obtained  by  Klein,  of  London,  who  asserts 
that  a  one  per  cent,  solution  of  the  mercuric  chloride  is  no  more  a  germicide  than 
is  vinegar  ;  but  the  evidence  to  the  contrary  is  so  strong  that  it  seems  almost  a  cer- 
tainty that  there  was  some  error  in  Klein's  experiment.  According  to  the  detailed 
experiment  of  Koch,  the  spores  of  B.  anthracis  are  absolutely  incapable  of  germi- 
nating in  a  proteid  solution  if  as  little  as  i  part  of  corrosive  sublimate  in  300,000  be 
present.  Sternberg  has  confirmed  the  experiments  of  Koch. 

It  must  be  remembered  that  corrosive  sublimate  is  so  readily  decomposed  by 
ammonia  and  other  substances  usually  present  in  a  mass  of  filth  that  it  is  not  availa- 
able  for  disinfectant  purposes  on  a  large  scale  ;  even  when  the  amount  of  organic 
matter  is  small,  the  usefulness  of  corrosive  sublimate  is  often  destroyed  by  its 
chemical  instability  :  thus,  it  should  not  be  employed  for  the  destruction  of  germs  in 
fecal  discharges.  A  standard  solution  of  i  part  in  1000  may  be  used  for  bedding, 
which  can  be  soaked  in  it,  for  washing  the  floors  and  walls  of  infected  apartments, 
and  for  disinfecting  the  hands  of  surgeons  and  gynaecologists.  After  the  corrosive 
sublimate  has  done  its  work  it  should  be  removed  by  free  washing  with  pure 
water.  Even  in  the  cases  just  spoken  of  corrosive  sublimate  is  often  inferior  to 
formaldehyde. 

For  various  surgical  purposes  the  sublimate  may  be  used  in  strengths 
varying  from  1:2000  to  i:  10,000.  It  is  well  to  add  to  the  solutions  of 
corrosive  sublimate  an  equal  quantity  of  ammonium  chloride  or  else  a 
small  proportion  of  tartaric  or  hydrochloric  acid,  as  these  substances 
lessen  the  liability  to  precipitation. 

HYDRARGYRUM  IODIDUM  RUBRUM.  U.  S. — The  biniodide  of  mer- 
cury, although  not  nearly  so  widely  employed  as  the  bichloride,  seems  to 
be  even  more  active  as  a  germicide.  According  to  the  experiments  of 
Burgess,1  a  i  :  5000  solution  of  the  biniodide  is  equivalent  in  strength  to 
a  i  :  2000  solution  of  the  bichloride.  Sternberg  has  found  that  a 
i  :  20,000  solution  of  the  biniodide  is  equivalent  to  i  :  15,000  solution  of 
the  bichloride  of  mercury. 

The  probable  reason  why  the  mercuric  iodide  has  not  come  into  use 
as  a  germicide  is  the  fact  that  it  is  almost  insoluble  in  water.  It  may  be 
readily  dissolved,  however,  by  the  addition  of  potassium  iodide  or 
lithium  iodide  to  the  solution.  Rosenberger  and  England "  suggest  the 
double  lithium  mercuric  iodide,  which  is  freely  soluble  in  water,  is  not  pre- 
cipitated by  the  fixed  alkalies,  and  according  to  their  experiments  is 
actively  germicidal. 

ARGENTI  NITRAS.  U.  S. — The  salts  of  silver  rank  next  to  the  salts 
of  mercury  as  the  most  powerful  germicides  we  possess.  According  to 
Miquel,  silver  nitrate  prevents  the  growth  of  atmospheric  germs  when 
present  in  the  proportion  of  i  part  to  12,500.  According  to  Boer,  a 
i  :  4000  solution  destroys  typhoid  bacillus  in  two  hours,  but  it  required  a 
i  :  2500  solution  to  kill  the  diphtheria  bacillus  in  the  same  time.  Behring 
found  that  a  i  :  10,000  solution  is  capable  of  destroying  the  anthrax 
spores  in  forty-eight  hours. 


DISINFECTANTS.  823 

Unfortunately,  the  silver  nitrate  is  an  extremely  unstable  salt,  being 
decomposed  by  the  alkalies,  the  mineral  acids,  albumin,  and  even  decom- 
posing in  the  air  on  exposure. 

Various  other  less  active  metallic  salts  have  been  used  in  the  past  as 
disinfectants  but  are  of  very  little  practical  value,  and  have  been  superseded 
by  the  numerous  active  modern  germicides.  Many  of  these  salts  act 
chiefly  by  the  capability  which  they  have  of  taking  sulphur  away  from  sul- 
phuretted gases,  and  thereby  lessening  odor;  so  that  they  are  rather 
deodorants  than  disinfectants.  The  most  used  of  these  disinfectants  are 
the  zinc  sulphate,  zinc  chloride,  and  lead  nitrate,  the  latter  forming  the 
basis  of  the  so-called  Ledoyeri  s  Disinfectant  Solution.  They  should,  'all 
of  them,  be  totally  disregarded.  Old  iron,  and  the  impure  ferrous  sul- 
phate {Copperas),  have  to  some  extent  resisted  modern  innovation,  and 
have  been  believed  to  have  the  power  of  oxidizing  organic  matter  and  of 
attacking  disease  germs,  which  makes  them  of  value.  Of  the  two,  cop- 
peras is  certainly  the  more  efficacious;  but  in  an  official  study  Dr.  A. 
J.  McLaughlin  *  has  shown  that  it  has  no  dominant  influence  over  putre- 
factive changes  unless  present  to  the  extent  of  five  per  cent. — that  its 
saturated  solution  does  not  affect  pathogenetic  organisms,  and  that  the 
same  solution  mixed  with  half  its  bulk  of  faeces  fails  to  disinfect  the  mass 
after  three  days. 

III.— HALOGENS. 

CHLORUM— CHLORINE. 

When  chlorine  is  brought  into  contact  with  organic  substances  and 
moisture,  it  unites  with  the  hydrogen  of  the  water  and  liberates  nascent 
oxygen,  which  rapidly  oxidizes  and  destroys  the  organic  compound. 
When  chlorine  comes  in  contact  with  sulphuretted  hydrogen,  it  removes  its 
hydrogen  and  thereby  destroys  it.  On  account  of  its  destructive  action 
on  organic  matter,  its  being  extremely  obnoxious  to  animal  life,  and  its 
comparative  expensiveness,  chlorine  gas  is  at  present  never  used  to  disin- 
fect rooms,  ships'  holds,  or  similar  places.  Inspired  in  sufficient  amount, 
chlorine  gas  produces,  both  in  man  and  in  the  lower  animals,  narcotism, 
and  finally  death  from  paralysis  of  the  respiratory  centre.*  The  germi- 
cidal  influence  of  chlorine  is  very  great. 

Fisher  and  Proskauer  found  that  dried  anthrax  spores  mantained  their  integrity 
for  one  hour  when  exposed  to  the  action  of  a  dry  chlorine  atmosphere  containing 
44.7  parts  of  chlorine  in  100  ;  but  when  the  air  and  the  spores  were  moist,  one  hour's 
exposure  to  an  atmosphere  containing  four  per  cent,  of  chlorine  produced  complete 
disinfection.  If  the  exposure  were  continued  for  three  hours,  one  per  cent,  of  chlo- 
rine was  an  efficient  germicide  :  and  if  the  spores  were  exposed  for  twenty-four  hours, 
the  effective  proportion  of  chlorine  could  be  still  further  reduced.  In  Sternberg's ' 
experiments,  six  hours'  exposure  of  vaccine  lymph  dried  upon  ivory  points  to  an 
atmosphere  containing  i  part  of  chlorine  in  200  was  sufficient  to  destroy  the  infec- 
tive property  of  the  lymph,  while  the  bacteria  of  putrid  urine  were  destroyed  after 

*  Consult  Arch.f.  Exper.  Path.  u.  P/iarm.,  xiii. 


824  EXTRANEOUS    REMEDIES. 

six  hours'  exposure  to  an  atmosphere  containing  i  part  of  chlorine  in  400.  Klein  * 
also  found  that  after  the  compartment  of  a  stable  in  which  pigs  had  died  of  swine- 
plague  had  been  thoroughly  fumigated  for  six  hours  with  chlorine,  healthy  animals 
could  be  placed  therein  with  safety. 

The  result  of  all  our  knowledge  upon  the  subject  of  the  disinfectant 
properties  of  chlorine,  iodine,  and  bromine  has  been  summed  up  by 
George  H.  Roh63  as  follows: 

1.  Chlorine  is  an  efficient  disinfectant  when  present  in  the  proportion  of  i  part 
in  100,  provided  the  air  and  the  objects  to  be  disinfected  are  in  a  moist  state  and 
the  exposure  continues  for  upwards  of  an  hour. 

2.  Chlorine,  when  used  in  sufficient  concentration  to  act  as  a  trustworthy  disin- 
fectant, injures  colored  fabrics  and  wearing  apparel. 

3.  Bromine  is  an  efficient  disinfectant  in  the  proportion  of  i  part  in  500,  pro- 
vided the  air  be  in  a  moist  state  and  the  exposure  continues  for  upwards  of  three 
hours. 

4.  Iodine,  in  solution,  is  an  efficient  disinfectant  in  the  proportion  of  i  part  in 
500,  the  exposure  continuing  for  two  hours. 

5.  The  use  of  chlorine,  and  in  a  greater  degree  of  bromine,  requires  consider- 
able experience  in  management :  when  carelessly  handled  these  elements  may  cause 
inconvenient  or  even  dangerous  symptoms  in  persons  using  them  ;  hence  they  are 
not  suitable  as  disinfectants  for  popular  use. 

For  purposes  of  practical  disinfection  chlorine  is  usually  obtained 
from  the  decomposition  of  one  of  the  hypochlorites. 

CALX  CHLORINATA.  U.S. — Chlorinated  Lime. — Bleaching-powder 
is  a  grayish-white  substance  occurring  in  powder  or  friable  lumps,  having 
a  hot,  acrid,  astringent  taste,  and  an  odor  resembling  that  of  chlorine.  It 
is  made  by  the  action  of  chlorine  upon  calcium  hydrate,  or  slaked  lime, 
and  should  contain  at  least  thirty  per  cent,  of  chlorine.  It  probably 
varies  in  its  chemical  constitution,  but,  according  to  the  most  recent 
views,  is  chiefly  composed  of  the  calcium  hypochlorite  and  chloride. 
When  exposed  to  the  air  it  slowly  evolves  hypochlorous  acid,  which, 
being  an  unstable  compound,  undergoes  spontaneous  decomposition,  and 
finally  sets  free  fourteen-fifteenths  of  its  chlorine.  When  an  acid  is  added 
to  chlorinated  lime,  the  chlorine  gas  is  rapidly  evolved.  If  a  specimen  of 
bleaching-powder  be  very  moist,  it  generally  contains  an  over-proportion 
of  the  deliquescent  calcium  chloride,  is  correspondingly  unable  to  liberate 
chlorine,  and  is  therefore  of  inferior  value. 

The  experiments  of  J.  R.  Duggan4  indicate  that  the  hypochlorites 
are  among  the  very  best  of  our  practical  germicides.  He  found  that  o.  25 
of  one  per  cent.  ( i  part  to  400)  of  chlorine  as  hypochlorite  is  an  effective 
germicide  even  when  allowed  to  act  for  only  two  minutes  ;  while  0.06  of 
one  per  cent.  (6  parts  to  10,000)  will  kill  the  spores  of  B.  anthracis  and 
B.  subtilis  in  two  hours. 

Bleaching-powder  usually  contains  from  twenty-five  to  forty  per  cent, 
of  available  chlorine.  For  most  purposes,  a  solution  made  with  i  part 


DISINFECTANTS. 


825 


of  this  preparation  to  100  parts  of  water  is  strong  enough,  for  it  will  con- 
tain from  0.25  to  0.40  of  one  per  cent,  of  chlorine  as  hypochlorite.  As  is 
stated  above,  the  smaller  of  these  quantities  is  sufficient  to  destroy  spores 
almost  instantly.  There  are  very  few  purposes  to  which  disinfectants  are 
applied  that  are  not  fulfilled  by  this  solution  of  i  to  100  of  bleaching- 
powder.  It  is  not  dangerously  poisonous,  is  said  not  to  injure  the  fibre  of 
clothing,  bedding,  etc. ,  and  is  very  cheap,  since  it  is  worth  only  about 
five  cents  per  pound.  For  the  destruction  of  disease-germs  in  urine,  fecal 
discharges,  sputum,  etc. ,  a  saturated  solution  of  bleaching -powder  appears 
to  be  in  all  respects  the  best  disinfectant  known :  for  the  purification  of 
cesspools,  sewers,  or  similar  receptacles,  or  of  masses  of  infected  filth,  chlo- 
rinated lime  stands  at  the  head  of  known  germicides.  * 

LIQUOR  SODE  CHLORINATE.  U.  S. — Solution  of  Chlorinated  Soda, 
Labarraque' s  Solution,  is  made  by  triturating  chlorinated  lime  with  a 

*  There  are  not  many  affairs  in  life  in  which  the  public  have  been  so  superabundantly 
fleeced  as  in  the  matter  of  disinfection.  A  most  extraordinary  part  of  this  swindling  is 
the  ease  with  which  distinguished  members  of  the  medical  profession  have  given  certifi- 
cates of  efficiency  and  value  to  comparatively  inert  and  extraordinarily  expensive  pro- 
prietary compounds.  Oddly  enough,  the  cat  that  has  drawn  the  chestnuts  out  of  the  fire 
for  avaricious  manufacturers  has  not  even  had  the  sense  to  smell  the  odor  of  its  own  paws 
when  burning !  There  is  no  proprietary  disinfectant  whose  value  corresponds  with  its 
selling  price.  The  following  table  was  compiled  some  years  since  by  A.  W.  Harlan,  of 
Chicago.  The  cost  represents  the  same  germicidal  power. 
Name.  Full  Cost. 

Corrosive  sublimate $o.oo^j 

Chlorine OIA 

Copper  sulphate oi>& 

Mercury  biniodide 02^ 

Mineral  acids 03$ 

Bromine 08 

Ammonia  gas 13$ 

Chloroform 14! 

Chromic  acid 15 

Potassium  chlorate i6| 

Silver  iodide 20 

Picric  acid 2o| 

Iodine 2if 

Silver  nitrate 22^ 

Potassium  permanganate y>\ 

Carbolic  acid 34f 

Benzoic  acid 5° 

Salicylic  acid 69 

Osmic  acid 4-62i90 

Thymic  acid 4-8° 

Anhydrous  prussic  acid      ....   n.oo 

Dr.  H.  C.  Wood,  Jr.,  has  compiled  for  the  present  edition  (i2th)  the  following  table 
on  the  basis  of  one  cent's  worth  of  corrosive  sublimate.  In  comparing  these  tables  it 
should  be  remembered  that  the  constitution  of  some  of  these  proprietary  disinfectants  has 
entirely  changed. 


Name.  Full  Cost. 

Corrosive  sublimate $o.oo$j 

Little's  sol.  phenyl 13.00 

Fifty  per  cent,  chlor.  zinc,  Squibb's  35.00 

Feuchtwanger's  disinfectant     .     .  35.00 
Ph6nol  sodique  (Hance  Bros.   & 

White) 51.00 

Platt's  chlorides 66.00 

Girondin 80.00 

Williamson's  sanitary  fluid  .     .     .  80.00 

Bromo-chloralum 80.00 

Blackman's  disinfectant  ....  96.00 
Squibb's  solution  impure  carbolic 

acid 112.50 

Burchardt's  disinfectant  ....  182.50 

Ph6nol  sodique,  French   ....  255.00 

Listerine 495-oo 


Name.  Full  Cost. 

Mercury  bichloride fo.oi 

Chlorinated  lime o.oj 

Cresol 0.06 

Bacillol 0.24 

Lysol 0.23 


Name.  Full  Cost. 

Creolin $0.50 

Platt's  chlorides 3.19 

Sanitas 11.72 

Listerine  .  .  62  81 


826  EXTRANEOUS    REMEDIES. 

solution  of  sodium  carbonate.  It  is  a  greenish-yellow  liquid,  having  a 
slight  odor  of  chlorine  and  a  sharp  saline  taste.  It  contains,  among 
other  substances,  sodium  hypochlorite,  and  possesses  the  therapeutic  and 
disinfectant  properties  of  the  chlorinated  compound.  Owing  to  its  liquid 
form,  its  comparative  freedom  from  odor,  and  its  depositing  sodium 
chloride  on  evaporation,  it  is  the  most  elegant  of  all  the  chlorine  prepa- 
rations for  use  in  the  sick-room.  Properly  diluted,  Labarraque's  solution 
may  be  employed  for  all  the  therapeutic  purposes  for  which  chlorine 
water  is  used.  The  dose  is  half  a  fluidrachm  to  two  fluidrachms  (2-7  C.c. ) 
in  half  a  tumblerful  of  water. 

According  to  Duggan,  a  two  per  cent,  solution  of  sodium  hypochlorite, 
representing  six  per  cent,  of  available  chlorine,  will  kill  the  anthrax  spores 
in  thirty  minutes.  Sternberg  found  that  it  required  seven  per  cent,  of  a 
commercial  Labarraque's  solution  to  kill  the  anthrax  spores  in  two  hours. 
It  must  be  remembered  that  the  commercial  preparations  of  both  chlor- 
inated lime  and  chlorinated  soda  vary  enormously  in  strength.  The 
Committee  on  Disinfection  of  the  American  Public  Health  Association, 
1885,  found  that  commercial  specimens  of  Liqitor  Sod<z  Chlorates  varied 
in  the  amount  of  available  chlorine  from  3.8  to  o.oi  per  cent,  and  chlo- 
rinated lime  from  33. 5  to  24.  i  per  cent,  of  available  chlorine. 

LIQUOR  CHLORI  COMPOSITUS.  U.  S. — Compound  Solution  of  Chlo- 
rine.— This  preparation,  which  replaces  the  old  chlorine  water,  is  made  by 
adding  hydrochloric  acid  to  a  solution  of  potassium  chlorate,  and  should 
contain  0.4  per  cent,  of  chlorine  with  some  chlorine  peroxide. 

Inlet  nally  chlorine  has  been  used  in  various  diseases,  especially  in 
maglignant  typhus,  but  at  present  is  rarely  if  ever  so  employed.  It  is 
stated  to  be  stimulant  and  tonic  to  the  stomach,  and  is  thought  by  some 
to  have  an  especial  influence  upon  the  liver.  It  has  been  employed  in 
chronic  hepatic  affections;  the  dose  is  half  a  fluidrachm  to  two  fluidrachms 
(2-7  C.c.)  in  three  or  four  fluidounces  of  water.  Chlorine  water  is  a 
powerful  irritant,  capable  of  producing  severe  inflammation  of  the  skin  or 
toxic  gastro-enteritis.  Properly  diluted,  it  forms  an  excellent  stimulant, 
disinfectant,  detergent  wash  for  foul  ulcers,  and  may  be  used  as  a  gargle 
in  malignant  sore  throat. 


IV.— OXIDIZING   DISINFECTANTS. 

POTASSII    PERMANGANAS— POTASSIUM     PERMANGANATE.    U.  S. 

This  salt  occurs  in  slender,  prismatic  crystals  of  a  dark  purple  color, 
inodorous,  of  a  sweetish,  disagreeable  taste,  and  forming  with  water  a 
solution  varying  from  a  purplish  black  to  a  beautiful  reddish  lilac,  accord- 
ing to  the  strength.  When  kept  dry,  and  not  exposed  to  the  atmosphere, 
potassium  permanganate  is  a  permanent  salt,  but  whenever  in  solution  it 
is  brought  into  contact  with  an  organic  body  it  at  once  gives  up  its  oxy- 


DISINFECTANTS.  827 

gen  to  the  latter  and  is  converted  into  potassa  and  black  manganese  oxide. 
The  statements  concerning  the  germicidal  power  of  potassium  per- 
manganate differ  very  materially. 

Sternburg,1  in  one  series  of  experiments,  found  that  0.12  per  cent,  solution 
would  kill  the  pus  cocci  in  two  hours  and  was  equivalent  to  0.8  per  cent,  solution 
of  carbolic  acid.  In  a  second  series  of  experiments  the  same  author  found  that  it 
required  a  two  per  cent,  solution  to  destroy  the  infection  of  mouse  septicaemia  as 
compared  with  a  1.2  per  cent,  solution  of  carbolic  acid.  According  to  Koch,  a  five 
per  cent,  solution  will  destroy  the  anthrax  spores  in  one  day. 

The  difference  in  the  results  of  experimenters  has  been  shown  by 
Sternberg  *  to  depend  upon  the  amount  of  organic  material  present  :  when 
this  is  large,  the  salt  is  so  rapidly  destroyed  by  the  organic  material  that 
it  has  no  chance  to  act  upon  the  contained  micro-organisms. 

It  affords  a  very  elegant  disinfectant  and  germicidal  wash  for  wounds, 
ulcers,  abscesses,  fetid  ozcena,  otorrhoea,  leucorrhcea,  etc.  In  dilute  solu- 
tion its  local  influence  is  stimulant  and  beneficial.  When  employed  in 
the  form  of  powder  it  even  affects  living  tissues,  acting  as  a  mild  caustic, 
and,  as  such,  may  often  be  applied  with  advantage  to  sloughing  ulcers. 
As  a  wash,  the  strength  may  vary  from  one  to  twenty  grains  to  the  ounce. 

P.  W.  MacDonald 2  has  found  the  potassium  permanganate  to  be 
very  effective  in  dysentery.  As  soon  as  the  diagnosis  is  reached,  the 
whole  of  the  lower  intestine  should  be  washed  out,  night  and  morning, 
with  a  solution  of  potassium  permanganate  (from  two  to  four  grains  to 
a  pint). 

The  injection  of  a  strong  solution  of  potassium  permanganate  in  the 
immediate  neighborhood  of  snake-bites  is  said  to  be  very  effective.  The 
action  of  the  permanganate  in  these  cases  is  that  of  a  destructive  oxidizant. 

In  a  series  of  laboratory  experiments  we  have  determined  that  potas- 
sium permanganate  is  capable  of  destroying  many  alkaloids,  acting  very 
rapidly  upon  cocaine  and  morphine,  but  slowly  upon  strychnine,  and 
Fodera 5  has  found  it  antidotal  also  to  helleborein  and  veratrine.  We  have 
also  found  that,  as  was  first  pointed  out  by  William  Moor,"  administered 
shortly  after  the  alkaloid  it  is  of  practical  value  in  morphine-poisoning. 
These  results  are  in  accordance  with  those  obtained  by  other  experi- 
menters, and  with  numerous  recorded  cases  of  opium-poisoning.*  The 
permanganate  should  be  given  in  small  doses  by  the  mouth  at  intervals 

*  Moor  (  Therapeitlische  Monatshcfte,  1903,  vol.  xvii,  page  562)  asserts  that  potassium 
permanganate  forms  with  albumin  a  substance  which  has  the  power  of  destroying  mor- 
phine, and  concludes,  therefore,  that  the  permanganate  is  capable  of  following  and  neu- 
tralizing the  poison  in  the  blood.  The  chemical  evidence,  however,  of  his  conclusions  is 
not  satisfactory,  and  we  have  found  that  the  hypodermic  injection  of  the  permanganate  in 
the  lower  animals  does  no  good  whatsoever  in  morphine-poisoning.  Fodera  asserts  that 
the  hypodermic  injection  of  potassium  permanganate  has  a  certain  antidotal  value  to 
morphine  and  strychnine  even  when  injected  at  a  distant  point,  but  that  if  the  alkaloid  is 
injected  before  the  potassium  permanganate,  the  antidote  has  no  effect  upon  the  course 
of  the  poisoning. 


828  EXTRANEOUS    REMEDIES. 

during  the  acute  stage  of  opium-poisoning,  as  it  has  been  shown  that  there 
is  a  continuous  excretion  from  the  walls  of  the  stomach  of  morphine,  which 
is  subsequently  reabsorbed  either  from  the  stomach  or  intestines. 

AQUA  HYDROGENII  DIOXIDI.  U.  S. — Solution  of  Hydrogen  Dioxide 
{Solution  of  Hydrogen  Peroxide}. — This  is  a  colorless,  odorless,  slightly 
acid,  aqueous  solution  of  Hydrogen  Dioxide  (H2O,  =  33.92)  containing, 
when  freshly  prepared,  about  three  per  cent.,  by  weight,  of  the  pure 
dioxide,  corresponding  to  about  ten  volumes  of  available  oxygen.  It  was 
discovered  by  The'nard  in  1818.  It  consists  of  water,  to  a  portion  of 
which,  by  the  presenting  to  it  of  oxygen  in  a  nascent  state,  an  additional 
atom  of  this  element  has  combined  with  the  hydrogen,  forming  the  diox- 
ide (HO)2,  or  H2Oj  ;  a  small  amount  of  free  acid*  is  always  left  in  it  as  a 
preservative.  It  is  apt  to  undergo  decomposition,  and  should  be  kept  in 
a  cold  place,  and  not  too  tightly  stoppered,  particularly  in  hot  weather, 
lest  there  should  be  such  a  brisk  evolution  of  oxygen  in  a  confined  space 
as  to  cause  an  explosion.  Hydrogen  dioxide  has  been  employed  to  a 
considerable  extent  in  the  arts  for  bleaching  and  cleansing  human  hair, 
engravings,  very  fine  textile  fabrics,  etc. 

THERAPEUTICS. — The  original  statement  of  B.  W.  Richardson,  that 
hydrogen  dioxide  is  a  powerful  oxidizant  of  organic  matters,  is  undoubt- 
edly correct.  It  is  an  active  coagulant  of  albumin,  and  when  brought  in 
contact  with  mucous  membranes  or  ulcerated  surfaces  evolves  gas,  at  the 
same  time  forming  a  dense  white  coating.  With  pus  it  effervesces  very 
actively,  and  rapidly  destroys  the  corpuscles,  which  immediately  become 
granular,  lose  their  shape,  and  break  up  into  detritus.  It  is  also  a  power- 
ful deodorant,  quickly  oxidizing  hydrogen  sulphide  and  similar  gases. 
Further,  it  is  a  very  powerful  germicide. 

Pane '  states  that  he  has  demonstrated  that  ( i )  Hydrogen  peroxide  in 
a  solution  of  i  to  100  has  an  energetic  germicidal  power.  (2)  The  solu- 
tion of  H2O2,  in  nutritive  substances,  i  to  352,  not  only  impedes  the 
development,  but  after  some  days  kills  the  spores  of  the  bacillus  of  char- 
bon.  (3)  The  solution  of  H2O2,  in  nutritive  substances,  from  i  to  352  to 
5052,  impedes  the  development  of  the  spores  of  the  bacilli  of  charbon, 
but  does  not  deprive  them  of  their  germinating  power  when  they  are 
transferred  to  another  nutritive  substance. 

Sternberg,  however,  believes  the  germicidal  value  of  hydrogen  per- 
oxide has  been  greatly  overestimated.  He  experimented  with  a  solu- 
tion of  hydrogen  peroxide  containing  4. 8  per  cent,  of  H.,O2  and  five  per 
cent,  of  sulphuric  acid.  In  his  experiments  this  solution  in  the  strength 
of  twenty  per  cent,  (representing  0.8  per  cent.  H.,O,)  killed  the  anthrax 
spores  in  two  hours,  and  ten  per  cent,  of  this  solution  destroyed  the  pus 
cocci  in  the  same  time  :  these  effects  Sternberg  believes  were  largely  due 
to  the  sulphuric  acid  which  he  has  found  will  destroy  the  pus  cocci  in  two 

*  The  existence  of  this  free  acid  endangers  the  teeth  when  the  Hydrogen  Dioxide 
Solution  is  used  habitually  as  a  tooth-wash. 


DISINFECTANTS.  829 

hours  in  proportion  of  i  :  200.  On  the  other  hand,  Gifford 6  found  that  an 
almost  neutral  fifteen  per  cent,  volume  solution  of  hydrogen  dioxide  (about 
four  per  cent,  by  weight)  destroyed  the  anthrax  spores  in  five  minutes  and 
the  pus  cocci  in  one  to  two  minutes.  This  solution  diluted  with  four 
parts  of  water  (0.8  per  cent.  H./).,)  failed  to  kill  the  pus  cocci  in  thirty 
minutes.  Gifford  asserts  that  the  bactericidal  effect  of  hydrogen  dioxide 
does  not  depend  upon  the  liberated  oxygen,  and  that  the  presence  of 
large  amounts  of  organic  matter  rapidly  decomposes  the  agent  and  inter- 
feres with  its  germicidal  properties. 

The  cost  of  hydrogen  dioxide  is  entirely  too  great  to  permit  the 
use  of  it  as  a  general  antiseptic,  or,  as  has  been  proposed,  for  the  puri- 
fication of  water.  On  the  other  hand,  for  some  of  the  purposes  of  the 
surgeon  it  is  invaluable,  its  liquid  form  making  it  especially  adapted  to 
the  cleansing  and  disinfection  of  putrid  cavities,  deep  infected  wounds, 
abscesses,  etc.  Its  influence  is  always  immediate  and  fugacious,  so  that 
it  cannot  replace  other  antiseptics  for  the  permanent  dressing  of  wounds. 
Theoretically,  it  is  capable  of  being  used  for  the  disinfecting  of  hands  and 
instruments. 

As  a  local  application  in  specific  inflammations  of  mucous  membranes 
hydrogen  peroxide  is  of  the  greatest  value.  In  scarlet  fever  and  diphtheria 
the  official  solution  may  be  applied  by  mop  to  the  pharynx,  often  with 
extraordinarily  good  results.  Diluted  one-half,  it  may  be  injected  into 
the  nasal  cavities  when  they  are  affected.  Injection  of  a  solution  of  from 
twenty  per  cent,  to  full  strength  has  received  commendation  in  the  treat- 
ment of  gonorrhoea  and  chancre.  The  official  solution  has  also  been  used 
with  alleged  great  success  as  a  local  styptic.  As  a  local  application  to 
mucous  membranes,  the  official  solution  may  be  used  ;  the  stronger  solu- 
tions are  sometimes  too  irritating. 

As  an  internal  remedy,  hydrogen  dioxide  was  strongly  recommended 
by  John  Day  in  diabetes,  low  fever,  and  other  typhoid  conditions.  On 
account  of  its  non-absorbability,  however,  it  is  probably  of  no  value  as  a 
systemic  remedy  in  these  or  any  other  diseases. 

In  H.  C.  Wood's  experiments  hydrogen  dioxide  was  found,  when 
injected  intravenously,  to  produce  immediate  wide-spread  coagulation  of 
the  blood  ;  and  put  into  the  stomach  in  solution  it  must  destroy  itself  by 
acting  upon  the  organic  contents  and  secretions.  It  is  certain  that  death 
has  been  caused  both  in  the  lower  animals  and  in  man  by  injecting  the 
solution  into  the  pleural  or  peritoneal  cavity.  It  has  seemed  to  us 
probable  that  these  deaths  were  due  to  shock,  the  outcome  of  the  intense 
local  irritation  of  the  pleura  or  peritoneum,  but  the  cases  reported  by  E. 
G.  Janeway  suggest  that  they  have  been  caused  by  embolic  arrest  of 
circulation  in  the  nerve-centres. 

In  the  case  reported  by  Laach,*  six  injections  into  the  pleural  cavity,  each  con- 
taining 0.8  cubic  centimetre  of  a  three  per  cent,  solution  of  hydrogen  peroxide, 
were  administered,  but  at  the  seventh  the  patient  complained  of  faintness,  the  pulse 
failed,  respiration  became  oppressed,  and  death  occurred  in  ten  minutes.  In  E.  G. 


830  EXTRANEOUS    REMEDIES. 

Janeway's  case  collapse  with  temporary  hemiplegia  followed  immediately  upon  the 
injection  of  hydrogen  peroxide  into  a  sacculated  empyema.  It  must  be  remem- 
bered, however,  that  there  are  on  record  a  number  of  cases  in  which  injection  of 
simple  water  into  the  pleura  has  produced  collapse,  paralysis,  or  convulsions  ;  so 
that  it  appears  doubtful  whether,  after  all,  the  hydrogen  peroxide  itself  and  not  the 
fluid  containing  it  has  been  the  cause  of  the  symptoms  in  the  case  just  alluded  to. 
On  the  other  hand,  probability  is  lent  to  the  theory  that  the  symptoms  above  spoken 
of  are  due  to  emboli  by  the  statements  of  Colasanti  and  Brugnola,*  that  hypodermic 
injections  of  the  dioxide  rapidly  kill  the  rabbit  by  causing  general  gaseous  oxygen- 
emboli  ;  that  in  the  dog  they  produce  a  local  emphysema,  followed  by  convulsions, 
urobilinuria,  and  other  disturbances. 

BENZOYL-ACETYL-PEROXIDE. — Benzozone. — Acetozone. — The  pure  peroxide 
occurs  in  a  white  crystalline  mass,  slightly  soluble  in  alcohol ;  prone  to  undergo 
decomposition  spontaneously,  and  capable  when  heated  in  a  confined  space,  or 
when  powdered  or  ground,  of  exploding.  It  is  slowly  dissolved  and  decomposed 
by  water,  and  in  contact  with  alkaloids  and  organic  matters  of  all  kinds  it  under- 
goes rapid  change  with  oxidation  of  the  decomposing  substances. 

Acetozone  of  the  markets  is  the  benzoyl-acetyl-peroxide  diluted  with  a  neutral 
drying  powder,  so  that  it  contains  fifty  per  cent,  of  the  pure  drug.  Fifteen  grains 
of  the  pure  drug,  or  thirty  grains  of  the  commercial  drug,  may  be  dissolved  in  one 
and  a  half  gallons  of  water,  thus  forming  an  active  solution  which  must,  howrever, 
be  used  within  thirty-six  hours  after  making.  Benzoyl-acetyl-peroxide  is  a  very 
active  germicide  ;  experiments  in  the  laboratories  of  the  United  States  Government 
in  the  Philippines  show  that  one  part  of  the  hydrolized  substance  to  177  of  water, 
containing  only  0.05  per  cent,  of  active  oxygen,  destroys  all  germs,  including 
spores,  almost  instantly,  and  even  at  a  dilution  of  i :  3000  vegetating  germs,  as  a 
rule,  are  killed  within  one  minute,  but  the  spores  require  a  longer  time.  On 
comparing  these  results  with  similar  ones  with  hydrogen  peroxide,  i :  1000,  and 
phenol  5  per  cent.,  it  was  shown  that  hydrogen  peroxide,  although  it  contained  ten 
times  as  much  active  oxygen  as  the  solution  of  benzoyl-acetyl-peroxide,  was  by  no 
means  as  effective,  and  the  same  may  be  said  of  phenol.  It  was  further  shown 
that  one  part  in  a  thousand  absolutely  destroys,  and  that  one  to  thirty  thousand 
distinctly  inhibits,  the  growth  of  the  comma  bacilli.  In  the  experiments  of  the  dis- 
covery of  acetozone  (Peer  and  Novy4),  one  drachm  of  it  a  day  given  to  a  dog 
weighing  eight  kilos  for  weeks  produced  no  sensible  effect,  and  it  is  probable  that 
it  is  not  taken  into  the  blood  at  all.  Charles  L.  Bliss  states  that  peroxide  is  elimi- 
nated in  the  form  of  hippuric  acid. 

Benzoyl-acetyl-peroxide  has  been  used  in  the  United  States  Philippine  hospitals 
as  an  intestinal  germicide  with  most  excellent  results  in  cholera,  given  in  double 
capsules  in  doses  from  0.2-0.32  grammes  (4-5  grains)  every  two  to  four  hours.  It 
was  found  that  when  the  stomach  was  full  at  the  time  of  administration  vomiting 
frequently  occurred,  probably  due  to  the  decomposition  of  the  peroxide  by  the 
organic  matter  present,  since  no  irritation  was  produced  when  the  stomach  was 
empty.  Benzoyl-acetyl-peroxide  has  been  employed  primarily  by  Wasdin,  and 
subsequently  by  Harris  and  others  (T.  G.,  1902-1903),  in  typhoid  fever,  with  al- 
leged most  extraordinary  results  in  the  reduction  of  the  local  and  general  symp- 
toms,— one  hundred  and  thirty  to  two  hundred  and  ten  grains  being  administered 
in  the  twenty-four  hours. 

Acetozone  has  been  used  locally  as  a  germicide  with  alleged  excellent  results 
in  gonorrhoea,  malignant  oedema,  tinea  tonsurans,  infected  ulcers,  and  similar  affec- 
tions. In  surgical  cases  the  dry  acetozone  may  be  applied  directly  to  the  wound. 
When  it  is  desired  to  especially  affect  the  intestinal  tract,  the  drug  should  be  given 
in  double  capsules  so  as  to  insure  as  far  as  may  be  its  entrance  unchanged  into  the 
duodenum. 


DISINFECTANTS.  831 


V.— CARBON  COMPOUNDS. 

PHENOL.     U.  S. 

Phenol  (  Carbolic  Acid,  Phenic  Acid,  Phenylic  Alcohol}  is  a  substance 
obtained  from  coal-tar  by  distilling  at  a  temperature  of  between  300°  and 
400°  F. ,  adding  to  the  distillate  a  hot  concentrated  solution  of  potassa, 
and,  after  this,  water,  separating  the  light  oily  matters  which  rise  to  the 
top,  and  adding  muriatic  acid  to  the  heavy  alkaline  bottom  layer,  when 
impure  carbolic  acid  separates.  This  impure  carbolic  acid  (AciDUM 
CARBOLICUM  CRUDUM,  U.  S. ,  1890)  is  of  a  dark  color,  and  contains 
several  congeneric  bodies,  especially  xylic  and  cresylic  acids.  These 
acids  are  as  active  germicides  as  is  phenol,  so  that  crude  carbolic  acid  is 
very  largely  used. 

PHENOL,  U.  S. ,  1900,  is  Hydroxybenzene  obtained  either  from  coal-tar 
or  made  synthetically  and  containing  at  least  ninety-six  per  cent,  of  the  pure 
principle.  It  occurs  at  ordinary  temperatures  in  minute,  colorless,  trans- 
parent plates,  or  long  rhomboidal  needles,  often  fused  into  a  mass,  having 
a  hot,  corrosive,  peculiar  taste  and  odor,  resembling  but  decidedly  dif- 
ferent from  those  of  creosote.  If,  on  exposure  to  the  air,  phenol  be- 
comes brown,  it  contains  impurities.  When  opportunity  is  afforded,  solid 
carbolic  acid  absorbs  water  from  the  atmosphere  and  melts  into  an  oily- 
looking,  colorless  liquid.  It  is  inflammable,  neutral  to  test-paper,  but 
combines  with  bases  ;  soluble  in  about  twenty  parts  of  water,  very  soluble 
in  alcohol,  acetic  acid,  ether,  glycerin,  and  the  volatile  and  fixed  oils. 
Nitric  acid  converts  it  into  picric  acid. 

PHENOL  LIQUEFACTUM.  U.  S. — Liquefied  Phenol  vs,  made  by  adding 
distilled  water  to  phenol  in  such  quantity  as  to  make  a  colorless  or  slightly 
reddish  liquid  containing  by  weight  86.4  per  cent,  of  phenol  and  13.6  per 
cent,  of  water. 

PHYSIOLOGICAL  ACTION. — Local  Action. — In  concentrated  form  car- 
bolic acid  is  a  mild  escharotic,  its  momentary  application  to  the  sound  skin 
producing  burning  pain  and  a  white  discoloration  which  changes  to  a 
reddish  stain,  gradually  fading  away  as  the  skin  desquamates.  If  the 
application  be  prolonged  an  eschar  forms. 

Carbolic  acid  in  sufficient  concentration  is  poisonous  to  all  forms  of 
protoplasm  ;  thus,  even  its  weak  solution  arrests  the  movements  in  cili- 
ated cells  and  in  white  blood-corpuscles  (T.  M.  Prudden,1  Labe"e2).  It 
appears,  however,  to  act  especially  upon  the  central  nervous  system  and 
upon  the  peripheral  nerve-endings:  as  was  simultaneously  pointed  out 
by  Erasmus  Wilson3  and  J.  H.  Bill,4  it  is  a  local  anaesthetic. 

Phenol  is  one  of  the  oldest  and  one  of  the  most  popular  of  all  germi- 
cides, but  its  power  and  reliability  are  usually  overestimated. 


832  EXTRANEOUS    REMEDIES. 

According  to  Van  Erlingen,74  a  five  per  cent,  solution  destroys  the  viability 
of  anthrax  spores  after  thirteen  days'  exposure.  On  the  other  hand,  Koch  has 
found  that  a  three  per  cent,  solution  of  carbolic  acid  will  destroy  the  anthrax  spores 
in  two  days.  According  to  Nocht,  the  activity  of  carbolic  acid  varies  very  greatly 
at  different  temperatures.  Thus  at  room  temperature  a  five  per  cent,  solution 
failed  to  destroy  the  anthrax  spores  after  several  days'  exposure,  but  when  kept  at 
a  temperature  of  37.5°  C.  the  same  solution  was  sufficient  in  three  hours.  It  is  evi- 
dent, however,  that  the  common  statement  that  five  per  cent,  solution  of  carbolic 
acid  is  equivalent  to  i  :  1000  of  corrosive  sublimate  is  not  true,  since  the  i  :  1000  solu- 
tion of  corrosive  sublimate  will  destroy  the  viability  of  the  anthrax  spores  in  two 
or  three  minutes. 

Of  the  less  resistant  germs,  phenol  is  an  efficient  destroyer. 

Thus,  Burgess 75  found  that  a  i :  40  solution  destroyed  the  bacillus  coli  communis 
in  five  minutes,  corresponding  to  i :  2000  corrosive  sublimate  solution.  In  Stern- 
berg's  experiments  0.8  per  cent,  destroyed  the  pus  cocci  in  two  hours'  exposure. 
Boer  has  determined  that  in  the  absence  of  spores  i :  300  solution  is  efficient  against 
the  anthrax  bacillus  in  two  hours. 

Absorption  and  Elimination. — Phenol  is  readily  absorbed  through  the 
gastro-intestinal  mucous  membrane  as  well  as  through  the  skin.  Hoppe- 
Seyler5  found  it  in  the  blood,  where  it  probably  circulates  as  an  alkaline 
carbolate  and  also  uncombined.  It  is  rapidly  eliminated,  having  been 
detected  in  the  urine  by  Alm6n,6  by  Patrouillard,7  by  Salkowski,8  by  Hoppe- 
Seyler,  by  Waldenstrom,9  and  by  Hauxmann9 :  Hoppe-Seyler  detected 
it  in  the  saliva,  and  it  probably  occurs  in  all  the  secretions.  The 
researches  of  Baumann,10  which  have  been  substantially  confirmed,  show 
that  the  carbolic  acid  is  changed  into  a  peculiar  sulphocarbolic  acid,  a 
sort  of  ether-sulph-acid,  having  the  formula  C6H.O.SO2.OH,  which  finally 
unites  with  alkalies  and  is  eliminated  as  a  sulphocarbolate  ;  when  large 
quantities  are  administered,  some  of  it  escapes  unchanged. 

In  a  fatal  case  of  poisoning  Patrouillard  obtained  an  oily  fluid,  believed  to  be 
pure  carbolic  acid,  by  shaking  the  urine  with  ether,  allowing  the  mixed  fluids  to 
separate,  and  removing  the  ethereal  layer  and  evaporating. 

Although,  as  stated,  phenol  is  to  some  extent  thrown  off  from  the 
system,  a  portion  of  it  is  burned  up  in  the  body.  The  black  coloring 
matter  of  the  characteristic  urine  of  carbolic-acid  poisoning  is  in  all  proba- 
bility an  educt  from  pheiiol,  formed  by  its  partial  oxidation. 

Hauxmann  has  proved  that  this  black  coloring  matter  is  not  altered  haematin  or 
any  fixed  coloring  principle,  by  finding  that  the  urine  is  cleared  up  by  heating  after 
the  addition  of  an  acid  ;  and  his  conclusion  is  corroborated  by  the  observation  of 
Stevenson,11  of  Guy's  Hospital,  who  determined  that  the  black  urine  does  not  contain 
more  than  a  normal  proportion  of  iron.  When  carbolic  acid  is  oxidized  outside  of 
the  body,  as  by  the  action  of  potassium  permanganate,  oxalic  acid  is  formed  ;  and 
Salkowski  has  shown  that  when  phenic  acid  is  given  to  animals  oxalic  acid  appears 
in  the  urine.  Other  observers  have,  however,  failed  to  detect  these  oxalates. 
Fr.  Schaffer,"  A.  Uerbach,11  and  E.  Baumann  and  C.  Preusse  u  found  that  the  phenol 


DISINFECTANTS.  833 

was  at  least  in  part  oxidized  into  hydrochinone  and  partly  into  a  greenish-black  sub- 
stance upon  which  the  coloring  of  the  urine  seems  to  depend.  The  researches  of 
L.  Brieger 15  led  him  to  the  conclusion  that  when  carbolic  acid  is  taken  in  not  too 
large  quantities  a  portion  of  it  unites  with  sulphuric  acid  and  a  portion  of  it  is  con- 
verted into  various  colored  oxidation  products,  some  of  which  are  very  poisonous. 
According  to  the  experiments  of  W.  Kochs,16  this  change  occurs  in  the  large 
abdominal  glandular  viscera. 

Schmiedeberg17  has  come  to  the  conclusion  that  no  phenol  is  oxidized 
in  the  body,  but  that  it  is  all  eliminated  in  combination  with  sulphuric 
acid,  or  to  a  less  extent  with  glyco-uronic  acid.  The  evidence  is,  how- 
ever, too  strong  against  this  view,  and  the  true  conclusion  seems  to  be 
that  when  carbolic  acid  is  taken  in  great  excess  it  is  in  part  eliminated  as 
carbolic  acid,  and  that  the  remainder  of  it  (the  whole  of  it  when  taken 
in  moderate  amount)  in  part  escapes  in  cmnbination  with  an  alkali  as 
sulphocarbo lie  and  glyco-uronic  acids  and  is  in  part  oxidized  in  the  system. 
Reale 18  affirms  that  when  the  sulphuric  acid  has  all  been  appropriated 
phosphoric  acid  is  attacked  by  the  phenol  and  a  phospho-carbolate  formed. 

Production  of  Carbolic  Acid  in  the  Animal. — Stadeler19  discovered  that  when 
sulphuric  acid  was  freely  added  to  cow's  urine  the  latter  yielded  upon  distillation 
carbolic  acid,  and  concluded  therefrom  that  normal  urine  contains  carbolic  acid. 
He  has  been  corroborated  by  Buliginsky  w  and  by  Hoppe-Seiler  ; J1  so  that  phenol 
is  certainly  a  constituent  not  only  of  the  urine  of  cattle,  but  also  of  that  of  men, 
dogs,  horses,  and  probably  other  animals.  Baumann  has  succeeded  in  producing 
carbolic  acid  out  of  fibrin  by  a  protracted  digestion  with  the  pancreatic  glandular 
substance,  and  Nencki  and  Brieger  have  found  that  it  is  constantly  present  in  normal 
human  faeces.  It  is  probable,  as  asserted  by  Salkowski,  that  the  acid  is  formed  in 
the  organism  as  a  late  product  of  the  pancreatic  digestion.  Its  elimination  by  the 
urine  is  enormously  increased  in  ileus  (one-hundredfold,  Salkowski) ,  and  dimin- 
ished in  anaemia,  phthisis,  scorbutus,  scrofula,  and  cancer  (Brieger).  Hoppe- 
Seyler's  theory,  that  the  acid  does  not  pre-exist  in  the  urine,  but  is  produced  out  of 
indican  during  the  processes  employed  for  separating  it,  is  not  tenable.  It  appears 
to  be  formed  from  the  albuminous  substances,  tyrosine  being  an  intermediate  prod- 
uct, since  Brieger  has  found  that  the  taking  of  large  doses  of  tyrosine  is  followed 
not  by  elimination  of  tyrosine  but  by  a  great  increase  of  the  urinary  phenol.  It  is 
quite  possible  that  the  phenol  is  formed  in  the  intestine  by  fermentative  changes,  as 
Baumann  has  noticed  the  closely  allied  substance  indol  produced  by  the  putrefac- 
tive changes  in  a  mixture  of  albuminous  substance  with  a  small  quantity  of  pancreas 
and  a  little  ammonium  carbonate.*  In  this  connection  it  is  interesting  to  note  that 
Christiani "  has  not  been  able  to  find  phenol  in  the  urine  of  chickens  fed  upon  vege- 
table diet,  although  a  notable  amount  is  present  when  a  flesh  diet  is  allowed.  In  a 
series  of  experiments  I.  Munk  M  obtained  three  grammes  as  the  average  excretion  of 
twenty-four  hours  from  a  horse. 

General  Effects. — The  largest  therapeutic  doses  of  carbolic  acid  pro- 
duce no  distinct  symptoms.  Reserving  the  details  as  to  the  effects  of 
toxic  doses  for  the  section  on  Toxicology,  it  is  sufficient  for  our  present 
purpose  to  state  that  the  prominent  symptoms  induced  by  lethal  doses 
are  disturbance  of  respiration,  stupor  deepening  into  coma,  rapid,  feeble 

*  See  Pfluger's  Archiv,  xii.  862 
53 


834  EXTRANEOUS    REMEDIES. 

pulse,  muscular  weakness,  abolished  reflexes,  collapse,  fall  of  tempera- 
ture, and  albuminous  or  bloody  urine,  ending  in  death  from  central  para- 
lytic asphyxia.  In  some  cases  convulsions  occur. 

According  to  Isidor  Neumann,14  to  Ernest  Labe"e,  and  to  Salkowski,  a  poison- 
ous dose  of  phenol  causes  in  the  frog  a  paralysis  which  usually  affects  first  the  hind 
legs,*  but  eventually  spreads  to  the  front  legs  and  involves  all  parts  of  the  body. 
After  a  time  there  are  developed  tetanic  convulsions,  which  are  apparently  reflex 
in  their  nature,  and  are  said  to  be  excited  by  external  stimuli  or  irritations. 

Upon  mammals  carbolic  acid  acts  in  very  much  the  same  way  as  it  does  upon 
the  batrachian.  According  to  W.  Kempster,25  in  the  mouse  and  rat  it  causes  in- 
tense muscular  weakness,  followed  by  violent  convulsions  and  stupor.  In  the 
rabbit  (Neumann,  Salkowski)  phenylic  alcohol  produces  muscular  weakness,  often 
accompanied  by  tremblings  and  restlessness,  at  last  giving  place  to  violent  convul- 
sions. As  has  been  pointed  out  by  Turtschaninow,26  the  tremors  first  commence 
as  peculiar  tremulous  contractions  of  isolated  muscles,  and  then  of  muscle  groups 
which  are  irregular,  and  not  at  all  symmetrical.  Early  in  the  poisoning  the  respi- 
ration is  affected  ;  and  death,  which  usually  occurs  in  the  midst  of  convulsions, 
is  owing  to  a  paralysis  of  the  respiration,  since  in  acute  cases  the  heart  is  found 
beating  continuously  immmediately  after  death.  According  to  the  researches  of 
Jules  Lemaire,27  in  the  dog  symptoms  very  similar  to  those  detailed  above  are 
caused  by  lethal  doses  of  the  drug  ;  and  Husemann 28  states  that  in  mammals  and 
in  birds  the  characteristic  phenomena  of  carbolic-acid  poisoning  are  clonic  convul- 
sions, sinking  of  the  temperature,  diminution  of  sensibility,  dyspnoea,  free  saliva- 
tion and  secretion  of  tears,  keratitis,  and  conjunctivitis.  According  to  the  latter 
authority,  albuminuria  and  haematuria  are  occasional  phenomena. 

Carbolic  acid,  being  a  universal  poison,  acts  upon  the  whole  system; 
so  that  the  detailed  study  of  its  physiological  effects  when  given  internally 
is  simply  an  endeavor  to  determine  what  tissues  are  most  susceptible  to 
its  influence. 

Nervous  System. — The  influence  of  carbolic  acid  on  the  cerebrum  is 
not  very  intense  in  the  lower  animals,  but  in  the  higher  species,  and 
especially  in  man,  results  in  the  early  production  of  stupor. 

The  convulsions  are  not  peripheral,  since  they  do  not  occur  in  a  limb 
whose  connection  with  the  spine  has  been  severed  by  division  of  the  nerve, 
and  do  take  place  in  a  leg  which  has  been  protected  against  the  local 
action  of  the  poison  by  tying  the  artery  (Salkowski,  Labe"e).  They  are, 
therefore,  either  cerebral  or  spinal.  Although  there  is  a  distinct  conflict 
of  evidence,  it  seems  established  that  the  convulsions  are  of  spinal  origin. 

Labe"e  and  J.  R.  Haynes  failed  to  get  them  after  section  of  the  cord,  but  in  the 
far  more  numerous  experiments,  upon  frogs  and  mammals,  of  Salkowski,  of  Berb 
and  Jogel,29  of  J.  S.  Stone,50  and  of  T.  Gies,sl  convulsions  occurred  after  destruction 
of  the  medulla,  section  of  the  cord,  and  other  operative  procedures  separating  the 
brain  from  the  lower  nervous  system.  The  failures  of  the  first-named  experiments 
are  explainable  by  the  facts  that  the  paralyzing  influences  of  carbolic  acid  are 
usually  first  manifested  upon  the  hind  legs,  and  that  very  large  doses  of  the  acid 
were  employed. 

*  According  to  Lemaire  when  a  frog  is  allowed  to  swim  in  water  impregnated  with 
carbolic  acid,  the  front  legs  are  first  affected. 


DISINFECTANTS.  835 

The  spinal  convulsions  are  accompanied  by  increased  reflex  activity, 
which  is  lost  as  the  paralytic  state  is  reached,  so  that  carbolic  acid  appears 
first  to  stimulate  and  then  depress  the  spinal  centres.  Stone  asserts  that 
the  stimulation  is  preceded  by  a  primary  depression,  due  to  stimulation 
of  Setschenow's  inhibitory  centre  in  the  medulla. 

In  carbolic-acid  poisoning  the  nerves  and  muscles  are  not  distinctly 
paralyzed  (Salkowski,  Hoppe-Seyler),  but  the  very  careful  experiments 
of  Gies  have  proved  that  the  muscles  are  less  sensitive  and  more  easily 
exhausted  than  is  normal. 

Circulation. — The  action  of  carbolic  acid  upon  the  heart  is  not  a  very 
marked  one,  but  there  can  be  little  doubt  that  in  sufficient  amount  the 
drug  depresses  the  heart. 

After  death  from  acute  poisoning  the  heart  is  usually  found  to  be  beating  regu- 
larly (Salkowski),  but  in  some  cases  of  slow  poisoning  the  death  has  seemed  to  be 
ultimately  caused  by  cardiac  diastolic  arrest.  In  Hoppe-Seyler's  manometrical 
studies  the  arterial  pressure  was  not  affected  until  convulsions  came  on,  when  it 
rose  from  the  effects  of  the  general  muscular  contraction.  It  afterwards  fell  very 
decidedly  and  permanently. 

Reduction  of  the  arterial  pressure  has  been  shown  by  Gies  to  be  the 
characteristic  effect  of  the  carbolic  acid  :  in  his  experiments  moderate 
doses  of  the  acid  failed  to  affect  the  pressure  after  section  of  the  cord, 
whilst  in  the  normal  animal  neither  asphyxia  nor  stimulation  of  a  sensi- 
tive nerve  elevated  the  lowered  pressure,  although  the  heart  was  beating 
forcibly, — facts  that  demonstrate  that  carbolic  acid  paralyzes  the  vaso- 
motor  centre  in  the  medulla  before  it  markedly  affects  the  heart. 

Respiration. — According  to  Salkowski,  Lab6e,  and  other  authorities, 
in  the  first  stages  of  phenol-poisoning  the  respiration  is  remarkably 
increased  in  frequency.  This  acceleration  Salkowski  believes  to  be  due 
partly  to  a  stimulant  action  upon  the  peripheral  vagi  and  partly  to  a 
similar  influence  upon  the  respiratory  centres. 

Salkowski  states  that  the  respirations  are  very  shallow,  and  that  the  diaphragm 
scarcely  participates  at  all  in  them,  but  that  if  the  cervical  vagi  be  cut  they  become 
much  slower,  deep,  and  regular.  On  the  other  hand,  if  carbolic  acid  be  given  to  an 
animal  suffering  from  section  of  the  pneumogastrics,  the  slow  breathing  is  very 
much  accelerated.  From  the  former  of  these  facts  the  German  investigator  draws 
the  conclusion  that  the  accelerated  breathing  produced  by  phenylic  alcohol  is  in 
part  due  to  a  stimulation  of  the  peripheral  vagi,  and  from  the  latter  fact  that  it 
partly  arises  from  a  similar  action  upon  the  respiratory  centres. 

The  final  paralysis  of  respiration  by  carbolic  acid  is  almost  certainly 
due  to  a  direct  action  upon  the  respiratory  centres. 

Temperature. — According  to  the  researches  of  Hobart  A.  Hare," 
phenol  injected  into  rabbits  produces  a  very  distinct  fall  in  the  bodily 
temperature,  which  is  usually,  but  not  always,  coincident  with  the  low- 
ering of  the  arterial  pressure.  In  the  calorimetric  studies  made  by  Hare 
the  action  upon  heat-production  and  heat-dissipation  in  the  normal  ani- 


836  EXTRANEOUS    REMEDIES. 

mal  appeared  to  be  various,  sometimes  production  and  sometimes  dissi- 
pation being  alone  affected,  while  in  other  cases  both  functions  were 
altered.  Some  years  ago  Emil  Erls 3S  found  that  in  mild  putrid  pois- 
oning in  animals  carbolic  acid  diminished  greatly  the  fever-heat ;  when 
the  poisoning  was  more  severe  it  had  no  influence.  The  calorimetric 
studies  made  by  Hare  upon  fevered  animals  were  fairly  constant  in  their 
results,  although  the  method  of  experimentation  was  not  satisfactory, 
because  the  acid  was  given  to  the  fevered  animals  at  a  time  when  it  was 
uncertain  what  would  have  been  the  production  of  heat  without  its  in- 
fluences. Nevertheless,  the  experiments  indicate  that  carbolic  acid  may 
affect  the  thermogenetic  functions  of  the  body  in  two  ways  :  first,  by  di- 
minishing the  production  of  heat ;  second,  by  increasing  the  dissipation 
of  heat. 

Effects  upon  Tissues. — Post-mortem  examinations  of  animals  killed  by 
carbolic  acid  have  yielded  varying  results.  In  Lemaire's  investigation, 
nothing  abnormal  was  detected  except  intense  injection  of  the  alimentary 
mucous  membrane,  a  pseudo-membranous  and  purulent  inflammation  of 
the  bronchial  tubes,  with  a  disseminated  lobular  pneumonia  and  con- 
gestion of  the  lungs  and  of  the  nerve-centres.  Bruckmiiller,  in  Neu- 
mann's investigation,  found  the  cells  of  the  liver  and  kidneys  in  a  state 
of  fatty  degeneration.  This  process,  which  seemingly  was  the  counter- 
part of  the  changes  in  phosphorus-poisoning,  was  always  more  advanced 
in  the  kidneys  than  in  the  liver.  Neumann  states  that  it  was  always 
present  in  his  numerous  autopsies,  and  that  it  is  a  constant  phenomenon  ; 
but  Salkowski  was  unable  to  find  it  in  a  number  of  examinations.  In 
man  the  post-mortem  appearances  are  very  much  the  same  as  in  ani- 
mals. If  the  acid  has  been  ingested  in  a  concentrated  form,  white, 
hardened  spots  are  found  upon  the  mucous  membrane  of  the  mouth, 
oesophagus,  stomach,  and  even  intestines.  They  are,  of  course,  due  to 
the  local  action  of  the  poison,  and  are  sometimes  blackish  in  the  centre, 
or  even  blackish  throughout,  and  very  generally  are  surrounded  by  a  red 
inflammatory  zone.  The  liver,  spleen,  kidneys,  and  indeed  all  the  or- 
gans, are  found  filled  with  dark,  imperfectly  coagulated  blood,  such  as  is 
habitually  found  after  death  from  asphyxia.  According  to  Husemann, 
the  fatty  degeneration  of  the  liver  and  kidneys  is  neither  in  man  nor  in 
animals  a  constant  or  characteristic  phenomenon  of  carbolic  acid  poison- 
ing. Reuder54  found  the  renal  epithelium  degenerated  in  a  man  who 
had  been  fatally  poisoned  by  the  drug. 

THERAPEUTICS. — In  the  doses  in  which  it  is  usually  given,  phenol 
exerts  no  perceptible  effect  upon  the  system.  It  has  been  used  to  a 
considerable  extent  in  zymotic  diseases  for  the  purpose  of  destroying 
the  germs  in  the  blood,  but  is  of  no  value  for  such  purpose.  There  is 
no  reason  for  believing  that  micrococci  or  bacteria  are  more  sensitive  to 
its  action  than  is  the  human  organism;  and  clinical  experience  in  zymotic 
diseases  has  certainly  demonstrated  the  uselessness  of  the  acid.  Our 
physiological  knowledge  conforms  with  clinical  experience  in  showing 


DISINFECTANTS.  837 

that  carbolic  acid  is  of  no  value  in  constitutional  diseases,  and  it  is  em- 
ployed directly  in  medicine  only  for  its  local  effects. 

Internally,  carbolic  acid  is  a  very  valuable  remedy  in  the  treatment  of 
various  forms  of  nervous  irritability  of  the  gastro-intestinal  mucous  mem- 
branes, especially  when  there  is  also  a  tendency  to  fermentative  changes 
in  the  food,  as  the  result  of  imperfect  digestion.  In  nervous  vomiting, 
and  in  gastrodynia,  it  may  be  given  in  doses  of  from  one  to  two  grains, 
repeated  at  intervals  varying  from  fifteen  minutes  to  two  hours,  according 
to  the  symptoms  of  the  case.  In  diarrhoea  of  irritation,  as  well  as  of 
relaxation,  it  is  often  of  the  greatest  service.  The  combination  of  one 
or  two  grains  of  carbolic  acid  with  ten  to  twenty  grains  of  bismuth,  given 
in  emulsion  or  in  capsules,  is  one  of  the  most  generally  useful  of  diar- 
rhoea mixtures.*  In  gangrene  of  the  lungs  the  internal  administration  of 
carbolic  acid  combined  with  the  use  of  a  weak  solution,  ten  drops  to  the 
ounce,  by  atomization,  is  said  to  be  of  great  service.  The  use  of  carbolic 
acid  as  an  antipyretic,  as  inaugurated  by  H.  M.  Desplats,35  has  not  found 
favor,  and  is  scarcely  justifiable. 

The  use  of  phenol  in  tetanus,  as  originally  proposed  by  Baccelli,  has 
in  a  number  of  cases  been  attended  by  apparently  beneficial  results. 
Ascoli  **  has  collected  thirty-four  cases  with  only  one  death. 

Exactly  how  phenol  acts  has  not  been  determined  ;  Heddaeus 8T  believes  that  it 
neutralizes  the  toxin  in  the  same  manner  as  does  the  antitoxin.  It  is  to  be  given  hypo- 
dermically  in  the  form  of  two  per  cent,  solution,  from  five  to  fifteen  grains  (0.3-1 
Gm.)  in  the  twenty-four  hours.  (See  H.  C.  Wood,  Jr.38)  Courmont  and  Doyon69 
in  a  research  upon  mice,  guinea-pigs,  and  rabbits  found  that  in  these  animals  car- 
bolic acid  is  useless  against  tetanus  infection. 

The  external  use  of  carbolic  acid  belongs  to  the  domain  of  surgery 
rather  than  of  medicine,  and  we  shall  discuss  it  very  briefly.  As  a  caustic, 
carbolic  acid  is  not  available  when  large  masses  of  tissue  are  to  be  de- 
stroyed, but  it  may  often  be  employed  with  advantage  against  condylomata 
and  similar  growths.  Even  in  such  cases,  to  be  efficient,  it  must  be  in 
the  most  concentrated  form.  In  diphtheria,  ulcerated  sore  throat,  and 
aphthous  stomatitis  its  concentrated  solution  in  glycerin  may  carefully  be 
applied,  by  means  of  a  camel' s-hair  brush  or  a  mop,  as  a  mild  caustic 
scarcely  capable  of  destroying  sound  tissue.  In  various  forms  of  indo- 
lent ulcer  and  in  ill-conditioned  wounds  carbolic  acid  affords  a  very  useful 
stimulant  application  ;  in  burns,  properly  diluted  with  oil  (ten  drops 
to  one  fluidounce),  it  is  one  of  the  very  best  remedies  that  can  be  used, 
relieving  pain  by  its  anaesthetic  properties  and  at  the  same  time  lessening 
suppuration  and  facilitating  cicatrization.  • 

The  use  of  carbolic  acid  as  a  local  anaesthetic  has  been  entirely  done 
away  with  by  the  discovery  of  the  powers  of  cocaine. 

*  In  dispensing  this,  if  capsules  be  used,  the  two  ingredients  should  be  thoroughly 
mixed  before  putting  in  :  if  an  emulsion  be  employed,  the  bottle  should  be  stood  on  its 
cork  or  laid  upon  its  side,  to  prevent  permanent  separation  of  the  bismuth. 


838  EXTRANEOUS    REMEDIES. 

So  far  as  we  know,  the  first  to  suggest  and  employ  deep  injections  of 
carbolic  acid  as  a  means  of  combating  deep-seated  inflammations  was  J. 
A.  Eames  ;39  but  the  method  has  been  especially  studied  by  C.  Hueter.40 

Hueter  employs  a  two  per  cent,  solution,  a  weaker  one  not  being  efficient  and 
a  stronger  one  endangering  the  coagulation  of  the  blood  and  of  the  exudation  in 
the  inflamed  tissue.  Of  this  solution  he  uses  at  one  time  never  more  than  half  a 
drachm,  and  generally  less  than  this.  After  anaesthetizing  the  skin  by  the  local  ap- 
plication of  carbolic  acid,  he  introduces  the  hollow  needle  into  the  centre  of  the 
inflammation  obliquely,  so  as  to  diminish  as  far  as  possible  the  chances  of  the  in- 
troduction of  air.  To  avoid  the  danger  of  throwing  the  acid  directly  into  the  circu- 
lation, the  needle  is  not  connected  with  the  syringe  until  it  is  seen  that  no  blood 
comes  out  through  it.  If  the  extent  of  inflamed  tissue  be  large,  several  injections 
are  practised  at  one  time  :  in  acute  cases  they  are  usually  repeated  twice  a  day,  in 
chronic  cases  every  day  or  every  other  day.  Hueter  has  made  about  a  thousand 
of  these  "  parenchymatous  injections,"  and  only  ten  times  has  any  inflammation 
been  excited  by  them.  The  pain  is  usually  very  slight,  and  the  relief  apparent  in 
one  or  two  days  at  most. 

In  chronic  synovitis  carbolic  acid  may  be  thrown  into  the  joint  once 
in  two  or  three  days,  and  the  method  has  been  practised  by  Hueter  with 
asserted  extraordinary  success  in  glandular  swellings  and  inflammations, 
phlegmons  of  all  grades  and  characters,  erysipelas,  poisoned  wounds, 
inflamed  burse,  hydrocele,  and  even  in  bone  disease. 

The  practice  has  been  followed  with  satisfaction  by  Aufrecht 41  in  ery- 
sipelas, by  Senator,"  Mader,45  and  Kunze"  in  acute  and  subacute  rheu- 
matism, by  Hagen  **  in  several  diverse  inflammations,  and  by  I.  Schmidt M 
in  chronic  synovitis.  These  injections  have  been  practised  by  Hagen  with 
asserted  excellent  results  in  severe  angina  (the  injections  were  in  the 
neighborhood  of  the  second  tracheal  cartilage):  by  Moses  K.  Taylor47 
in  one  hundred  and  fifty  cases  of  buboes  and  other  enlarged  glands,  with 
uniform  success:  by  Mutschler78  with  success  in  anthrax.  The  total  evi- 
dence seems  to  show  that  this  method  of  treatment  is  both  safe  and 
effective. 

TOXICOLOGY. — Probably  on  account  of  the  ease  with  which  it  is  pro- 
cured and  the  quickness  of  its  action,  carbolic  acid  is  among  the  most 
popular  of  poisons.  According  to  Harris,48  out  of  five  hundred  and 
forty-nine  fatal  cases  of  poisoning  with  it  which  occurred  in  England  during 
four  years  four  hundred  and  twenty  were  suicidal. 

The  symptoms  usually  appear  in  a  very  short  time  after  the  ingestion 
of  the  poison,  and  when  the  dose  has  been  sufficient  may  develop  so 
rapidly  that  death  occurs  within  three  minutes.  Usually  the  patient  lives 
from  one  to  ten  hours,  and  life  has  been  protracted  for  sixty  hours.* 

Taylor49  records  a  case  in  which  about  an  ounce  is  supposed  to  have  been 
ingested,  and  in  which  the  man  fell  in  a  stupor  within  ten  seconds  after  taking  the 

*  Case,  Sydenham  Soc.  Year-Book,  1871-72,  446 ;  amount  taken,  one  and  a  half 
ounces  of  the  commercial  acid. 


DISINFECTANTS.  839 

fatal  draught,  two  minutes  afterwards  was  totally  unconscious,  pulseless,  with  irreg- 
ular distant  gasping  respirations,  and  in  less  than  a  minute  later  was  dead,  appar- 
ently from  cardiac  paralysis,  since  the  impulse  of  the  heart  was  entirely  lost  before 
the  cessation  of  respiration. 

Usually,  but  not  always,  a  burning  pain  is  first  felt  in  the  mouth, 
oesophagus,  and  stomach,  followed  in  a  few  minutes  by  nausea,  cold 
sweats,*  and  stupor  deepening  rapidly  into  insensibility  and  collapse. 
During  the  period  of  insensibility,  complete  abolition  of  reflex  move- 
ments and  anaesthesia  of  the  mucous  membranes  have  sometimes  been 
noted  :f  indeed,  it  is  scarcely  doubtful  that  in  all  cases  both  sensibility 
and  reflex  movements  are  profoundly  affected.  Convulsions  are  only 
exceptionally  present.  The  symptoms  of  collapse  are  usually  well  de- 
veloped, and  the  pulse  is  generally  feeble  and  very  frequent,  but  has 
been  recorded  as  being  reduced  to  from  40  to  50  per  minute.  J  Haemo- 
globinuria  has  been  noted.  Dyspnoea  is  often  extreme  ;  the  respira- 
tions may  be  stertorous,  are  usually  very  rapid,  and,  in  the  advanced 
stages,  shallow.  In  very  rapid  cases  they  are  irregular  and  suspended 
at  intervals.  Total  temporary  amaurosis,  with  contraction  of  the  pupil, 
has  been  noted. § 

In  some  cases  of  carbolic  acid  poisoning  a  great  amendment  has 
occurred  and  consciousness  been  restored,  but  after  some  hours  rather 
sudden  fatal  collapse  has  come  on.||  The  minimum  fatal  dose  of  car- 
bolic acid  is  not  known  ;  but  half  an  ounce  has  several  times  caused 
death,^[  and  a  little  over  a  drachm  is  reported  to  have  killed  a  man  sixty- 
four  years  old  ; M  in  a  case  of  puerperal  metro-peritonitis  fifty  drops  con- 
tributed towards  the  fatal  result  (A.  D.  L.  Napier51). 

The  free  external  use  of  carbolic  acid  is  by  no  means  devoid  of 
danger ;  Falckson,52  after  two  hours'  exposure  to  carbolic  acid  spray, 
recovered  from  his  urine  thirty  grains  of  carbolic  acid,  and  he  describes 
a  marasmus  or  chronic  poisoning  resulting  from  the  surgical  use  of  the 
remedy.  The  symptoms  are  said  to  be  headache,  loss  of  appetite, 
bronchial  irritation,  which  finally  may  become  very  severe,  severe  pains 
in  the  region  of  the  kidney,  recurring  vomiting,  pruritus,  or  various 
paraesthesise,  and  loss  of  power  in  the  legs.  (See  also  Wallace.58) 

A  single  vaginal  injection  has  produced  very  severe  constitutional  results.5* 
R.  Kohler 55  reports  the  cases  of  two  journeymen  joiners,  suffering  from  scabies, 
who  applied  externally  each  about  a  half-ounce  of  carbolic  acid,  in  watery  solution. 
One  of  them  was  found  dead.  His  fellow,  who  suffered  from  unconsciousness  and 

*  The  excessive  sweating  sometimes  seen  in  carbolic-acid  poisoning  Th.  Gies  believes 
to  be  of  central  origin,  since  in  a  poisoned  cat  with  one  sciatic  nerve  cut  no  sweat  came 
from  the  injured  part. 

t  Case,  Journ.  de  Pharnt.  et  de  Chim.,  Dec.  1871. 

%  Case,  Med.  Times  and  Gaz.,  April,  1871. 

§  Case,  Berlin.  Klin.  Wochenschr.,  xix.  748. 

||  Case,  Brit.  Med.  Journ.,  Feb.  1861. 

U  Med.  Times  and  Gazette,  1870,  ii.  474 ;  Phila.  Med.  and  Surg.  Rep.,  Jan.  1870; 
Lancet,  1878,  ii.  510. 


84o  EXTRANEOUS    REMEDIES. 

drunken  delirium  ending  in  unquiet  sleep,  after  his  recovery  stated  that  directly 
after  rubbing  himself  with  the  solution  he  had  giddiness,  that  seven  or  eight  minutes 
later  his  companion  complained  of  burning,  but  that  of  what  took  place  after  this 
he  knew  nothing.* 

It  is  scarcely  necessary  to  refer  in  detail  to  cases  in  which  serious  re- 
sults have  followed  the  surgical  use  of  carbolic  acid,  t  A  very  severe 
case  of  poisoning  is  recorded,  in  an  infant,06  produced  by  the  use  of  car- 
bolized  cotton  wool.  The  local  application  of  carbolic  acid  has  in  a 
number  of  instances  been  followed  by  local  gangrene,  £  which  A.  Franken- 
burger 51  has  attributed  to  thrombosis,  but  Harrington 77  believes  has  been 
due  to  a  direct  chemical  action. 

The  diagnosis  of  carbolic-acid  poisoning  during  life  ought  in  most 
cases  to  be  practicable  ;  for,  although  the  symptoms  simulate  some  forms 
of  apoplexy  too  closely  for  the  diagnosis  to  be  made  from  them,  very 
generally  the  odor  of  the  drug  can  be  perceived  about  the  person  of  the 
victim,  and  close  examination  of  the  mouth  will  nearly  always  reveal 
traces  of  the  local  action  of  the  phenol,  in  the  form  of  white,  hardened,  or 
corrugated  patches  of  mucous  membrane.  Either  these  or  a  blackish 
urine  in  conjunction  with  the  symptoms  are  diagnostic.  After  death 
a  strong  odor  of  phenol  can  almost  always  be  perceived  when  the 
body  is  opened,  and  the  mucous  membrane  of  the  stomach  affords  very 
reliable  evidence  as  to  the  cause  of  death.  According  to  A.  Hiller,  the 
urine  of  phenol-poisoning  as  first  passed  varies  from  a  clear  yellow  to  a 
golden  yellow,  and  upon  standing  in  the  air  becomes  dark  olive  and  finally 
often  blackish-green.  Sometimes  it  is  grass-green,  but  it  may  appear  to 
be  normal.58  This  carbolic  acid  urine,  if  treated  with  nitric  acid  and 
afterwards  with  potassa,  becomes,  after  a  certain  degree  of  concentration, 
blood-red  or  brown-red,  changing  through  pea-green  to  violet.  Carbolic 
acid  mixed  with  urine  does  not  answer  this  test.59§  The  absence  of  car- 
bolic acid  urine  proves  that  the  case  is  not  one  of  poisoning.  Baumann 
and  Hueter**  declare  that  the  earliest  symptom  of  the  poisoning  is  the 
disappearance  of  the  sulphates  from  the  urine.  || 

In  a  case  of  carbolic-acid  poisoning  emetics  are  generally  useless, 
owing  to  the  existing  paralysis  of  the  stomach,  and  the  stomach-pump 
must  be  employed  to  empty  the  viscus.  As  antidotal  to  carbolic  acid, 
alkalies  in  excess  have  been  specially  commended  by  Husemann,  who 

*  For  other  fatal  cases  consult  Bull.  Thcrap.,  IXXY.  285. 

f  Consult  British  Medical  Journal,  March  i,  1873, — death  from  absorption  by  a 
wound  four  inches  long ;  New  York  Medical  Gazette,  April,  1871  ;  British  Medical 
Journal,  1868,  220,— two  fatal  cases;  Med.  Times  and  Gas.,  1878,  ii.  461 ;  Wiener  Med. 
Wochenschrift,  1879,  xxix.  1233. 

J  For  cases,  seeMfd.  Times  and  Gazette  1870,  ii. ;  L'Abeille  Med.,  1871 ;  Med.  News, 
1890,  i. ;  Bull.  Soc.  Med.  d.  Hop.  d.  Paris,  1889,  vi.;  Schmidt's  Jahrb.,  cclvii.  197. 

%  For  method  of  detecting  carbolic  acid  in  urine,  see  Land.  Med.  Rec.,  1877,  455. 

||  To  detect  the  diminution  of  sulphates  in  the  urine,  remove  any  albumin  present  by 
boiling,  acidify  with  acetic  acid,  and  add  barium  chloride  in  excess.  This  reagent  gives 
a  milky  cloud  of  barium  sulphate  in  the  presence  of  sulphates,  but  a  mere  haze  or  no 
alteration  in  carbolic-acid  poisoning. 


DISINFECTANTS.  841 

employs  saccharated  lime  ;  *  whilst  formerly  the  free  ingestron  of  oils 
was  strongly  urged  by  authorities.  In  1878  Baumann  and  Hueter61 
stated  that  if  a  dilute  sulphuric  acid  or  a  soluble  sulphate  be  given  freely 
to  the  animal  poisoned  with  carbolic  acid  the  latter  will  be  converted  into 
a  harmless  sulphocarbolic  acid.f 

The  present  evidence  regarding  the  antidotal  value  of  the  sulphates  in  car- 
bolic-acid poisoning  is  not  entirely  clear.  David  Cerna,"  in  an  elaborate  series 
of  experiments  upon  animals,  employed  the  magnesium  sulphate  with  entire 
success.  Cafawy6*  reached  experimental  results  similar  to  those  of  Cerna.  S. 
Tauber,64  however,  challenged  the  correctness  of  this,  affirming  that  the  doses  used 
by  Cerna  were  not  really  lethal,  and  giving  a  number  of  experiments  in  which 
neither  the  sodium  sulphate  nor  the  pyrosulphate  evinced  any  antidotal  influence 
in  the  poisoned  rabbits.  He  further  concluded,  as  the  result  of  his  experiments, 
that  the  sodium  sulphite  is  of  distinctly  antidotal  value.  On  the  other  hand,  Jos. 
Szydlowsky65  saved  a  pulseless  and  apparently  dying  child,  ten  hours  after  the 
ingestion  of  the  carbolic  acid,  by  hypodermic  injections  of  ether  and  the  adminis- 
tration of  dilute  sulphuric  acid  and  sodium  sulphate. 

The  best  conclusion  that  can  be  formed  from  the  present  evidence  is 
that  which  was  reached  in  1 894  by  Pio  Marfori "  as  the  result  of  his  own 
experiments, — namely,  that  the  soluble  sulphates,  given  either  through 
the  gastro-intestinal  canal  or  injected  hypodermically,  are  distinctly  anti- 
dotal to  carbolic  acid,  but  that  there  is  a  limitation  to  their  power,  so  that 
if  too  much  phenol  has  been  taken  the  sulphates  will  prove  of  no  value. 

Within  the  last  few  years  alcohol  has  been  highly  recommended  by 
Phelps,  Fraser,  and  others,  as  an  efficient  antidote  against  carbolic  acid. 
There  seems  to  be  no  doubt  concerning  the  value  of  alcohol  in  overcoming 
the  local  irritant  influence  of  carbolic  acid,  but  according  to  Ascher T6  its 
effect  does  not  depend  upon  any  chemical  antagonism  between  the  two, 
but  is  simply  a  process  of  dilution  plus  the  astringent  action  of  alcohol. 
This  has  been  confirmed  by  Clarke  and  Brown  "  who  found  that  mixtures 
of  phenol  and  alcohol  were  as  toxic  as  watery  solutions  of  phenol,  but  that 
when  the  stomach  was  washed  out  with  dilute  alcohol  the  local  lesions 
were  almost  absent. 

The  practical  treatment  of  phenol  poisoning  should  be  lavage  of  the 
stomach  with  ten  per  cent,  solution  of  alcohol  (or  whiskey),  followed  by 
administration  of  magnesium  sulphate,  the  use  of  stimulants  as  indicated 
and  the  treatment  of  the  subsequent  gastritis  with  demulcent  remedies. 

GLYCERITUM  PHENOLIS.  U.  S. — Glycerite  of  Phenol  is  a  twenty 
per  cent,  solution  of  phenol  in  glycerin,  and  is  an  excellent  preparation. 

*  Dissolve  sixteen  parts  of  sugar  in  forty  parts  of  distilled  water,  and  add  five  parts 
of  caustic  lime  ;  digest  for  three  days,  stirring  from  time  to  time,  filter,  and  evaporate  to 
dryness.  The  product  thus  obtained  dissolves  easily  in  water. 

t  For  a  study  of  sulphocarbolic  acid,  see  La  Tribune  Med.,  July,  1884,  328.  M.  F. 
Vigier  affirms  that,  while  not  poisonous  to  the  higher  animals,  it  is  an  active  antiferment. 
M.  Rabuteau  (Compt.-Rend.  Soc.  Biol.,  1882,  iii.  42)  finds  that  the  acid  is  simply  a  feeble 
purgative. 


842  EXTRANEOUS    REMEDIES. 

Dose.    Phenol  gr.   i-ii    (0.07-0.13  Gm. );     Phenol  Liquefactum,  n\,i-ii 
(0.05-0.1  C.c. );   Glyceritum  Phenolis,rc^\-^  (0.25-0.5  C.c. ). 

CREOSOTUM.  U.  S.— CREOSOTE— CREASOTE. 

This  substance  b  defined  by  the  U.  S.  Pharmacopoeia  to  be  a  mixture 
of  phenols,  chiefly  guaiacol  and  creosol,  obtained  during  the  distillation 
of  wood-tar,  preferably  of  that  derived  from  the  beech  {Fagus  syhatica, 
Linn£).  The  creosote  of  commerce  is  an  oleaginous  liquid,  colorless,  or 
brownish  or  reddish,  having  a  caustic  taste  and  a  penetrating  disagree- 
able odor,  which  whilst  resembling  that  of  carbolic  acid  markedly  differs 
from  it  in  being  more  smoky.  It  is  neither  acid  nor  alkaline  in  reaction, 
and  forms  in  water  two  solutions,  having  respectively  the  strength  of  one 
to  ten  and  one  to  eighty.  As  it  occurs  in  commerce  it  varies  in  consti- 
tution; and,  indeed,  even  creosote  conforming  to  the  official  tests  varies 
in  the  proportion  of  its  ingredients.  It  is  stated  that  the  beech- wood 
creosote  ranges  in  the  amount  of  guaiacol  from  sixty  to  ninety  per  cent. 
It  has  been  much  confused  with  carbolic  acid,  and  for  many  years  most 
of  the  creosote  of  the  drug-stores  was  an  impure  carbolic  acid.  For 
the  tests  distinguishing  creosote  from  carbolic  acid,  see  United  States 
Dispensatory. 

PHYSIOLOGICAL  ACTION. — The  physiological  effects  of  creosote  have 
never  been  carefully  and  thoroughly  studied.  It  certainly  rivals  carbolic 
acid  in  its  antiseptic  power. 

Sternberg  has  found  that  a  i :  200  solution  of  creosote  destroyed  the  pus  cocci 
in  two  hours'  exposure.  Bucholz10  ranks  creosote  as  superior  to  carbolic  acid, 
but  inferior  to  salicylic  acid. 

Creosote  is,  when  applied  locally,  a  paralyzant  to  the  nerves,  and 
probably  to  all  higher  tissues  ;  indeed,  it  has  been  generally  believed  to 
be  physiologically  almost  identical  with  carbolic  acid.  It  differs,  however, 
greatly  from  carbolic  acid  in  its  toxicity  and  in  its  therapeutic  usefulness. 

The  symptoms  of  creosote-poisoning  are  similar  to  those  caused 
by  carbolic  acid, — namely,  burning  in  the  gullet  and  stomach,  vertigo, 
faintness,  unconsciousness,  collapse,  blackish  urine,  stertorous  breathing, 
and  great  cardiac  depression.  Zawadzki  *  reports  a  death  alleged  to  have 
been  produced  by  three  six-drop  doses  of  creosote,  taken  in  the  twenty- 
four  hours. 

Freudenthal *  reports  the  case  of  a  woman  who  took  six  hundred  drops  of 
creosote  in  a  very  short  time,  the  ingestion  being  followed  almost  immediately  by 
unconsciousness,  with  intense  trismus,  contracted,  immobile  pupils,  and  general 
cyanosis,  but  in  which  recovery-  occurred  without  the  administration  of  remedies. 

*  For  other  cases  of  creosote-poisoning,  see  Muller  (  Wurtemb.  Correspondenz-Blatt, 
1869),  T.  Stevenson  ( Guy's  Hasp.  Rep.,  1875,  xx.  144),  Piirckhauer  (Friedreich's  Blatter 
f.  Gericht.  Med.,  1883,  430),  F.  Grinell  (Med.  News,  xl.  345)  Manouvriez  (Soc.  Med.- 
Mgale  de  France,  vii.  108),  and  Faisans  (Bull.  Med.  Soc.  Med.  d1  Hop.  de  Paris,  1896). 


DISINFECTANTS.  843 

He  further  states  that  subsequently  this  same  patient,  by  increasing  the  dose  of 
creosote,  was  able  to  take  five  hundred  drops  daily  without  ill  effect.* 

The  absorption  and  elimination  of  creosote  are  very  rapid. 

Saillet,*  within  the  nine  hours  following  the  administration  of  eight  centi- 
grammes, obtained  from  the  urine  forty-eight  milligrammes  ;  after  sixteen  centi- 
grammes, one  hundred  and  eleven  milligrammes  ;  and  it  would  appear  that  about 
two-thirds  of  the  dose  escapes  from  the  body  through  the  kidneys  in  the  time  men- 
tioned. Imbert*  recovered  one  gramme  of  guaiacol  from  the  urine  after  the  hypo- 
dermic injection  of  two  grammes  ;  after  two  grammes  of  a  mixture  of  guaiacol  and 
creosol,  sixty  centigrammes  ;  and  so  on  :  so  that  it  would  appear  that  a  portion  of 
the  creosote  is  destroyed  in  the  body.  This  conclusion  is,  however,  rendered 
doubtful  by  the  fact  that  the  creosote  escapes  through  other  channels  than  the 
kidneys. 

Creosote  has  been  found  abundant  in  the  sputa  of  phthisical  patients, 
and,  indeed,  Catillon 5  affirms  that  it  is  chiefly  thrown  off  through  the 
lungs.  It  occurs  in  the  urine  probably  in  part  as  oxidized  educts,  but 
chiefly  as  creosol  and  guaiacol  sulphates  :  so  that,  as  shown  by  Hobert  A. 
Hare,'  sulphuric  acid  and  the  soluble  sulphates  are  antidotal  to  it.* 

THERAPEUTICS. — Creosote  has  been  used  in  medicine,  first,  as  a 
germicide  ;  second,  for  its  local  effects.  On  account  of  its  supposed 
influence  on  the  tubercle  bacillus  it  was  introduced  in  the  treatment  of 
phthisis.  It  has  received  in  this  disease  much  commendation,  espe- 
cially from  Sommerbrodt,  who  has  reported  thirteen  years' s  experience 
with  it.  He  insists  on  the  necessity  of  the  purity  of  the  creosote,  and  of 
the  use  of  large  doses — one  to  two  grammes  per  day — for  many  months 
or  years.  Our  own  experience  is  in  accord  with  the  general  drift  of  the 
clinical  results  obtained  by  authors,  in  showing  that  whilst  creosote  is  a 
valuable  remedy  in  phthisis,  it  is  not  a  specific,  and  will  rarely,  if  ever, 
bring  about  a  cure  :  that  it  acts  in  these  cases  by  poisoning  the  bacilli  is 
beyond  belief.  Any  such  action  must  be  purely  local, — i.e.,  due  to 
creosote  excreted  in  the  lung, — since  F.  Holscher  and  Richard  SeifertT 
found  that  in  young  rabbits  and  dogs  to  which  guaiacol  had  been  freely 
given  the  serum  of  the  blood  was  at  no  time  capable  of  checking  the 
development  of  bacilli  in  agar-agar  :  the  conclusion  of  the  experimenters 
just  named,  that  guaiacol  during  absorption  becomes  converted  into  an 
albuminous  compound  which  has  no  influence  upon  the  lower  organisms, 

*  Imbert  finds  that  the  proportion  of  creosote  eliminated  diminishes  with  the  increase 
of  the  dose.  Thus,  after  an  enema  of  one  gramme,  fifty-four  to  sixty  per  cent,  was  found 
in  the  urine ;  after  two  grammes,  forty-eight  per  cent. ;  after  four  grammes,  thirty  per  cent. 
When  four  grammes  were  administered,  the  expectorations  showed  its  presence  for  twelve 
hours.  After  a  subcutaneous  injection,  Imbert  was  not  able  to  recover  from  the  excretions 
more  of  the  creosote  than  after  it  had  been  given  by  enema.  Although  there  were  severe 
persistent  pain  and  swelling,  no  suppuration  or  sloughing  ever  followed  these  injections. 
Imbert  also  found  that  the  elimination  ceased  at  the  end  of  twelve  hours  after  large  as 
well  as  small  doses  (Bull.  Gin.  Thfrap.,  1892,  cxxii.).  For  methods  of  finding  creosote 
in  the  urine,  see  also  Bull.  G£n.  Therap.,  May,  1892. 


844  EXTRANEOUS    REMEDIES. 

is  plausible.  The  theory  that  creosote  exercises  an  antiseptic  effect  in 
plithisis  is  also  contradicted  by  the  researches  of  Schill  and  Fischer 
(quoted  by  Sternberg),  who  found  that  a  one  per  cent,  solution  of  creosote 
failed  to  destroy  the  tubercle  bacilli  in  the  sputum  after  two  hours'  ex- 
posure. It  seems  to  be  established  that  creosote  is  largely  eliminated 
with  the  sputa  ;  but  Bogdonovitch  and  other  clinicians  or  experimenters 
have  found  the  bacilli  abundant  and  active  in  the  sputa  of  phthisical 
persons  taking  the  remedy.  Brissonet 8  and  Holscher  and  Seifert  present 
evidence  to  show  that  guaiacol  neutralizes  in  the  blood  those  poisonous 
products  of  bacillary  growth  which  are  the  cause  of  the  fever,  sweating, 
disordered  digestion,  etc. ,  of  the  phthisical  patient ;  in  other  words,  that 
creosote  acts  chemically  in  the  blood.  At  present  this  seems  to  be  nothing 
more  than  an  ingenious  theory.  In  our  experience,  creosote  acts  most 
favorably  in  cases  with  very  free  expectoration,  and  we  have  seen  it  do  so 
much  good  in  simple  pulmonary  catarrh  not  resting  upon  a  tubercular 
basis,  that  we  believe  it  to  be  simply  a  valuable  alterative,  stimulant  ex- 
pectorant, which  also  may  do  good  by  checking  intestinal  fermentation 
and  improving  the  digestion. 

On  account  of  its  local  action  as  a  nerve  paralyzant,  creosote  is  fre- 
quently employed  with  great  advantage  in  nausea,  vomiting,  or  diarrhoea 
dependent  upon  excessive  irritability,  without  acute  inflammation,  of  the 
gastric  or  intestinal  mucous  membrane  ;  it  has  thus  been  successfully 
used  in  the  vomiting  of  pregnancy  or  of  hysteria,  in  cholera  morbus, 
cholera  infantum,  lienteric  diarrhoea,  typhoid  fever,  and  even  in  dysentery. 
When  in  these  cases  there  is  a  tendency  to  fermentation  of  the  contents 
of  the  stomach  or  bowels,  creosote  is  especially  valuable,  and  may  often 
be  combined  advantageously  with  an  alkali  or  chalk.  Whether  it  is  in 
these  affections  superior  to  carbolic  acid  is  doubtful. 

Externally,  creosote  has  been  employed  for  exactly  the  same  purposes 
as  has  carbolic  acid.  The  skin  diseases  to  the  treatment  of  which  creo- 
sote has  been  supposed  to  be  best  suited  are  those  of  a  scaly  character. 
In  burns  its  efficacy  has  been  insisted  on,  especially  when  there  is  excess 
of  suppuration  or  of  fungous  granulations.  Also  in  chilblains  it  is  stated 
to  be  a  useful  application.  Mixed  with  four  parts  of  lard,  it  is  said  to 
have  proved  very  serviceable  in  erysipelas.  When  applied  to  wounds  it 
acts  as  a  haemostatic,  stopping  the  capillary  hemorrhage,  but  it  pos- 
sesses no  power  to  arrest  the  bleeding  from  large  vessels.  Accordingly, 
creosote-water  has  been  applied  locally  in  menorrhagia,  and  to  arrest 
uterine  hemorrhage  and  the  bleeding  from  leech-bites.  Wherever  there 
are  foul  ulcers,  gangrenous  surfaces,  or  inflamed  serous,  mucous,  or 
glandular  tissues  giving  rise  to  fetid  discharges,  creosote  may  be  sub- 
stituted for  carbolic  acid  ;  as  examples  may  be  mentioned  fetid  leucor- 
rhcea,  puerperal  metritis,  fetid  otorrhoea,  putrid  or  diphtheritic  sore  throat, 
chronic  empyema,  and  chronic  fistula.  The  strength  of  the  application 
may  vary  from  that  of  pure  creosote  to  a  one  per  cent,  solution. 

Th«  most  important  use  of  creosote  is  as  a  stimulating  expectorant, 


DISINFECTANTS.  845 

not  only  in  pulmonary  tuberculosis,  but  in  other  forms  of  chronic  bronchitis, 
especially  in  which  there  is  a  large  amount  of  expectoration. 

On  the  theory  of  the  antiseptic  action  of  creosote  in  phthisis  numerous 
attempts  have  been  made  to  bring  creosote  in  direct  contact  with  the 
tuberculous  lung.  Thus,  its  solution  in  oil  has  been  by  various  prac- 
titioners injected  directly  into  the  pulmonary  parenchyma.9  Dor's 
method  consisted  of  injecting  into  the  trachea  from  five-tenths  to  two 
centimetres  of  the  five  per  cent,  solution  of  creosote  in  olive  oil  pre- 
viously boiled.  Neither  theory  nor  result  seems,  however,  to  justify  these 
violent  procedures.  The  inhalations  of  the  vapor  of  creosote  have  been 
very  largely  used  by  means  of  respirateurs  or  other  mechanical  con- 
trivances, and  the  British  Pharmacopoeia  recognizes  VAPOR  CREOSOTI 
(twelve  minims  to  eight  fluidounces  of  boiling  water). 

The  ordinary  dose  of  creosote  is  from  three  to  five  minims  (0.12-0.3 
C.  c. )  three  to  six  times  a  day,  in  chronic  cases  increased  to  one  or  even 
two  fluidounces  a  day,  as  borne  by  the  patient.  Creosote  in  capsules 
should  be  taken  upon  a  full  stomach.  Large  doses  of  it  should  always  be 
freely  diluted  with  water  and  glycerin,  or  milk,  or  cod-liver  or  other  oils, 
to  avoid  local  irritation.  The  hypodermic  use  of  creosote,  as  practised  by 
Perom  in  phthisis  (ten  per  cent,  solution  in  oil  of  sweet  almonds),  is  not  to 
be  favored.  Dose  of  creosote-water  (AQUA  CREOSOTI — one  per  cent. 
U.  S. ),  half  to  one  fluidrachm  (2-4  C.c. ). 

CREOSOTUM  CARBONICUM.  —  Creosote  Carbonate.  —  Creosotal.  —  A 
mixture  of  the  phenol-carbonates  of  the  several  constituents  of  creo- 
sote, containing  about  ninety  per  cent,  of  creosote.  It  is  a  thick, 
oleaginous,  pale  yellow,  almost  tasteless  liquid,  insoluble  in  water,  soluble 
in  fatty  substances.  It  has  been  highly  recommended,  especially  by  Ley- 
den,  as  a  substitute  for  pure  creosote  in  phthisis,  bronchitis,  and  other  pul- 
monic  diseases,  as  having  the  advantages  of  being  less  disagreeable  to  the 
taste  and  better  tolerated  by  the  digestive  apparatus.  It  is  decomposed 
in  the  system,  and  is  capable  of  producing  blackish  urine.  It  is,  how- 
ever, much  less  poisonous  than  is  creosote,  and  probably  when  large  doses 
are  exhibited  escapes  in  part  from  the  alimentary  canal.  Fifteen  drachms 
of  it  are  asserted  to  have  been  given  in  a  day  without  unpleasant  symp- 
toms; and  it  has  been  used  hypodermically  after  warming,  so  as  to  in- 
crease its  fluidity.  It  may  be  given  in  capsules,  or  preferably  in  emulsion 
in  milk.  Ordinary  dose,  five  to  ten  grains  (0.3-0.6  Gm.),  administered 
three  to  six  times  a  day. 

GUAIACOL.  U.  S. — Methyl  Pyrocatechin. — Monomethyl  Ether. — 
Guaiacol  is  a  phenoloid  body,  constituting  from  sixty  to  ninety  per 
cent,  of  creosote,  from  which  it  may  be  obtained  by  fractional  distillation, 
or  it  may  be  prepared  synthetically.  It  occurs  as  a  colorless  crystalline 
solid,  and  also  as  a  syrupy  liquid  of  an  agreeable  aromatic  odor.  It  is 
soluble  in  fifty-three  parts  of  water  and  very  freely  in  alcohol  and  ether. 


846  EXTRANEOUS    REMEDIES. 

Guaiacol  acts  in  concentrated  form  as  an  irritant  and  as  a  germicide. 
As  originally  pointed  out  by  Andre,  it  has  also  distinct  anaesthetic  properties 
which  are  not,  however,  sufficiently  pronounced  to  make  the  drug  useful 
as  a  local  anaesthetic.  In  the  experiments  of  J.  Kuprianow  l  guaiacol  was 
found  to  be  distinctly  inferior  to  creosote  and  to  carbolic  acid  in  general 
germicidal  influence,  but  to  be  especially  poisonous  to  the  tubercle  bacillus. 

Guaiacol  is  absorbed  and  eliminated  with  the  greatest  rapidity. 
Linossier  and  Lannois 3  were  able  to  recognize  it  in  urine  passed  fifteen 
minutes  after  its  local  application  to  the  skin,  and  to  obtain  from  the  urine 
of  the  next  twenty-four  hours  nearly  half  of  the  whole  amount  used.  In 
the  experiments  of  Eschle s  the  greatest  part  of  the  ingested  guaiacol  or 
guaiacol  carbonate  was  eliminated  within  twenty-four  hours,  about  half  of 
it  going  out  with  the  urine  in  combination  with  sulphuric  acid;  of  the 
remainder  the  greater  part  was  eliminated  as  glycuronic  acid. 

The  general  physiological  action  of  guaiacol  has  not  been  studied  to 
any  extent,  but  appears  to  be  similar  to  but  less  powerful  than  that  of 
carbolic  acid. 

The  suggestion  of  Guinard 4  that  guaiacol  be  used  externally  as  an 
antipyretic  in  phthisis  has  led  to  its  trial  in  pneumonia,  typhoid  fever, 
and  other  acute  diseases.  The  thoroughly  cleansed  skin  of  the  abdomen 
or  chest  is  painted  by  means  of  a  camel' s-hair  brush  with  from  twenty  to 
fifty  minims,  and  an  impermeable  dressing  applied  to  prevent  evaporation. 
The  fall  of  temperature  produced  by  the  guaiacol  used  in  the  manner 
described  follows  with  great  certainty,  but  has  too  often  been  excessive 
and  accompanied  by  pronounced  collapse  to  allow  the  drug  to  be  con- 
sidered a  practical  antipyretic. 

Guaiacol  is  used  as  a  substitute  for  creosote  in  tubercular  and  other 
chronic  catarrhs,  and  is  very  effective.  It  is  also  used  locally  in  lupus  and 
other  forms  of  surgical  tuberculosis.  Thus,  in  tuberculosis  of  the  bladder, 
and  even  in  chronic  cystitis,  from  fifteen  to  thirty  minims  of  a  five  to  twenty 
per  cent,  solution  in  sterilized  olive  oil  may  be  injected  daily  into  the  blad- 
der. Inhalations  of  the  aqueous  solution  (i  :  600)  have  been  considerably 
used  in  pulmonic  tuberculosis,  but  it  is  not  probable  they  have  any  effect 
except  upon  the  catarrh  of  the  mucous  membranes.  Dose,  five  to  ten 
minims,  which  may  be  given  in  soft  capsules,  preferably  in  emulsion. 

GUAIACOLIS  CARBONAS.  U.  S.  —  Guaiacol  Carbonate. — Duotal. — 
This  derivative  of  guaiacol  occurs  as  a  neutral,  white,  almost  tasteless  and 
odorless  crystalline  powder,  insoluble  in  water,  soluble  in  forty-eight  parts 
of  alcohol.  It  is  much  used  as  a  substitute  for  guaiacol  on  account  of  its 
freedom  from  taste  and  of  its  being  less  irritant.  It  is,  however,  much 
less  active  than  is  guaiacol,  both  as  a  local  and  general  agent.  In  the 
experiments  of  W.  Hesse5  it  was  found  to  be  so  slightly  poisonous  that 
it  seems  probable  that  when  it  is  taken  internally  much  of  it  passes 
through  the  alimentary  canal  unabsorbed.  Guaiacol  carbonate  is  com- 
monly given  in  dose  oi  fifteen  to  twenty  grains  (1-1.33  Gm. ). 


DISINFECTANTS.  847 

PHENYLIS  SALICYLAS.  U.  S. — Salol. — This  is  a  white,  nearly  taste- 
less, insoluble  crystalline  powder,  which  is  prepared  by  replacing  one  atom 
of  the  hydrogen  of  salicylate  acid  by  phenol.  It  is  decomposed  by  alkalies, 
and,  consequently,  is  broken  up  in  the  intestinal  tract,  yielding  about 
thirty-six  per  cent,  of  phenol,  and  sixty-four  per  cent,  of  salicylic  acid. 
Although  less  powerful  as  a  poison  than  are  its  united  ingredients,  prob- 
ably because  it  is  broken  up  slowly  in  the  intestines  and  escapes  with  the 
faeces  to  some  extent  unchanged,  salol  is  capable  of  producing  concurrent 
symptoms  of  salicylic-acid  and  carbolic-acid  poisoning.  *  Kumagawa  has 
found  that  it  increases  nitrogenous  elimination. 

Salol  was  originally  introduced  into  medicine  by  Sahli1  as  an  anti- 
rheumatic,  but  is  at  present  employed  almost  solely  as  an  intestinal  disin- 
fectant. According  to  Lesnik  *  it  has  practically  no  influence  upon  ordi- 
nary bacteria.  Its  effectiveness  as  an  intestinal  antiseptic  evidently 
depends  upon  the  carbolic  and  salicylic  acid,  which  are  liberated  by  its 
decomposition.  In  the  experiments  of  Kumagawa2  on  animals,  large 
doses  of  salol  failed  to  lessen  the  elimination  of  indican  by  the  urine  or 
the  number  of  bacteria  in  the  intestines  ;  nevertheless,  in  typhoid  fever, 
intestinal  indigestion,  and  allied  complaints,  salol  may  be  considered  as 
probably  the  most  effective  of  our  intestinal  antiseptics. 

Externally  salol  has  been  used  as  an  antiseptic  dressing,  but  is  of  very 
little  value. 

One  hundred  grains  a  day  of  salol  have  frequently  been  given  without 
serious  effect,  probably  because  the  larger  proportion  of  the  salol  has 
escaped  unchanged  with  the  faeces.  Hesselbach  claims  that  the  long- 
continued  use  of  salol  is  dangerous  when  the  kidneys  are  diseased, 
on  account  of  the  irritating  influence  of  carbolic  acid  on  these  organs. 
The  ordinary  dose  is  from  ten  to  fifteen  grains  (0.6-1  Gm. );  as  an  intes- 
tinal disinfectant,  administered  in  capsules  one  hour  after  meals. 

Geosote  and  Eosote  are  respectively  valerianic  acid  compounds  of  guaiacol  and 
creosote,  which  have  been  highly  commended  by  Heifer  in  doses  of  0.2-0.4  grammes 
three  to  four  times  a  day,  given  in  capsules. 

ORTHOGUAIACOL-SULPHONIC  ACID,  or  Theocol,  occurs  as  a  white,  micro-crys- 
talline, odorless,  permanent  powder,  of  a  faint  bitter  saline  taste,  soluble  in  water 
and  dilute  alcohol.  It  has  a  powerful  reducing  action  on  silver  salts  and  ferric  com- 
pounds, and  at  once  decolorizes  permanganate  solution.  Hatch6  claims  it  to  be  of 
great  value  in  bronchitis,  pneumonia,  phthisis,  and  all  forms  of  infective  inflamma- 
tions of  the  lungs.  He  thinks  it  attacks  the  bacilli. 

*  Ewald  affirms,  as  the  result  of  experimental  research,  that  salol  is  not  decom- 
posed in  the  stomach,  but  immediately  upon  its  entrance  into  the  intestines,  and  that 
the  products  of  decomposition  appear  almost  at  once  in  the  urine  in  the  form  of  sali- 
cyluric  acid,  which  yields  a  red  precipitate  with  ferric  chloride.  Ewald  proposes  taking 
advantage  of  this  fact  in  order  to  determine  the  rate  at  which  food  passes  from  the 
stomach.  The  urine  of  seven  persons  in  sound  health  afforded  the  salicyluric  acid  reac- 
tion in  from  one-half  to  three-quarters  of  an  hour  after  the  ingestion  of  the  drug,  but  in 
seven  cases  of  gastric  dilatation  with  weakness  of  the  muscular  coat  of  the  stomach  two 
to  three  hours  were  required.  More  recent  clinical  experiments,  however,  throw  great 
doubt  upon  the  value  of  the  test  (see  Berlin.  Klin.  Wochensch.,  1889,  xxvi.,  975). 


848  EXTRANEOUS    REMEDIES. 

CRESOL.  U.  S. — Homologous  with  phenol  are  the  three  isomeric 
compounds,  orthocresol,  metacresol,  and  paracresol,  a  mixture  of  which  is 
recognized  by  the  U.  S.  Pharmacopoeia  under  the  name  of  Cresol.  It 
occurs  as  a  colorless  or  straw-colored  refractive  phenol-like  liquid,  soluble 
in  sixty  parts  of  water  and  miscible  in  all  proportions  with  alcohol  and 
glycerin.  It  is  a  later  product  of  the  fractional  distillation  of  coal-tar,  and 
is  practically  the  substance  which  has  long  been  known  in  commerce  as 
Cresol,  Crcsylol,  or  Cresylic  Acid. 

Cresol  is  soluble  in  sixty  parts  of  water  at  25°  C. ,  but  the  official 
LIQUOR  CRESOLIS  COMPOSITUS,  U.  S.(  is  miscible  with  water  in  all  pro- 
portions. In  the  compound  solution  of  cresol,  as  in  the  various  proprietary 
preparations  of  cresol,  the  germicide  is  kept  in  solution  by  means  of  alkali 
and  linseed  oil;  it  contains  fifty  per  cent,  of  cresol  and  is  the  official 
non-proprietary  form  of  cresol.  Lysol  is  a  dark-brown,  oily  liquid, 
which,  according  to  Schwyzer,1  contains  fifty  per  cent,  of  cresols,  held  in 
solution  by  means  of  an  alkali,  linseed  oil,  and  glycerin.  The  addition 
of  lime  salts  and  the  use  of  hard  water  in  making  solutions  of  compound 
solution  of  cresol,  on  account  of  the  insolubility  of  the  lime  soaps,  produces 
a  turbidity  of  the  solution,  which,  however,  it  is  claimed  does  not  interfere 
with  its  germicidal  activity. 

Although  it  seems  established  that  cresol  is  a  more  active  germicide 
than  phenol,  what  knowledge  we  have  of  its  physiological  activities  is  de- 
rived so  largely  from  studies  of  proprietary  preparations,  whose  real  com- 
bination is  a  matter  of  doubt,  and  is  so  imperfect  that  positive  conclusions 
as  to  its  exact  value  must  be  drawn  with  caution  especially  as  the  three 
cresols  differ  somewhat  in  their  properties. 

Henri  Delplanque8  affirms  that  cresol  is  stronger  than  carbolic  .acid  as  a  germi- 
cide and  has  only  one-fourth  of  its  toxicity.  Frankel9  found  that  a  0.3  percent, 
solution  of  cresol  destroyed  the  staphylococcus  aureus,  and  the  streptococcus 
erysipelatus  in  five  minutes,  while  a  two  per  cent,  solution  of  carbolic  acid  required 
fifteen  minutes  to  accomplish  the  same  result.  The  statement  of  Frankel  that  the 
compound  of  cresol  with  sulphuric  acid  is  soluble  in  water,  scarcely  irritant,  and 
more  powerful  as  a  disinfectant  than  is  carbolic  acid,  seems  to  us  highly  improbable. 
Weiss  found  that  a  three-fourths  per  cent,  solution  of  lysol  destroyed  various 
bacteria  (pus  cocci,  typhoid  bacillus,  etc.)  in  five  minutes,  and  the  anthrax  spores 
in  one  hour.  According  to  the  results  of  Burgess,5  however,  lysol  is  not  greatly 
superior  to  carbolic  acid.  That  cresol  is  poisonous  has  been  proven  by  Faust,10  and 
Fries 2  has  collected  thirty-eight  cases  of  lysol-poisoning,  of  which  eleven  were  from 
external  use,  with  four  deaths;  twenty-seven  from  internal  use  with  thirteen  deaths. 
He  places  the  toxic  dose  at  about  4-5  c.c.  for  children,  and  10-12  c.c.  for  adults. 
Maass '  affirms  that  lysol  is  eight  times  less  poisonous  than  is  carbolic  acid,  and 
one-half  as  poisonous  as  creolin.  Tollens  "  has  shown  that  although  paracresol  is 
slightly  less  toxic  than  phenol  commercial  cresol  is  fully  as  poisonous  if  not  more 
so  than  carbolic  acid,  whether  in  watery  or  saponaceous  solution.  It  is  certainly 
less  caustic  in  concentrated  solution  than  is  carbolic  acid. 

The  symptoms  of  cresol-poisoning  are  nausea  and  vomiting,  general 
depression  with  stupor,  fall  of  the  bodily  temperature,  smoky,  albuminous 


DISINFECTANTS.  849 

urine,  ending  in  fatal  cases  in  coma  and  collapse.  The  compound  solu- 
tion of  cresol  offers  a  valuable  substitute  for  carbolic  acid  as  a  germicide  in 
all  purposes  in  which  the  older  preparation  is  useful.  It  has  the  advantages 
of  greater  power,  less  irritation,  and  lower  toxicity.  Its  saponaceous  char- 
acter makes  it  especially  valuable  in  cleansing  the  skin  or  the  surgeon's 
hands.  Its  extremely  unpleasant  taste  and  odor  lessens  its  value  in  intes- 
tinal putrefaction  and  diarrhoeas,  as  recommended  by  Maass  and  Vonder- 
goldz.4  In  these  affections,  however,  pure  cresol  may  be  given  in  capsules 
in  doses  of  from  two  to  three  minims. 

CREOLIN  is  a  soluble  preparation,  containing,  according  to  Pfreuger1  2.7  per 
cent,  of  phenols,  mostly  cresol,  suspended  by  means  of  resin  soap.  It  has  been 
asserted  that  creolin  is  not  poisonous,  Jessner  stating  that  he  had  given  one  hundred 
and  twenty  grains  (7.77  Gm. )  to  a  man  without  production  of  distinct  symptoms. 
It  is  almost  certain,  however,  that  its  apparent  lack  of  toxicity  depends  upon  its 
non-absorption,  due  to  insolubility  ;  and  human  poisoning  has  been  caused  by  it. 

Bitter10  has  seen  restlessness,  anxiety,  nausea,  amblyopia,  and  a  tendency  to 
syncope,  with  a  peculiar  strong  taste  of  tea  or  smoke,  produced  by  the  drug.  The 
urine  in  some  of  his  cases  was  dark  and  highly  albuminous,  acute  nephritis 
having  evidently  set  in.  Fliesburg71  details  a  case  of  a  three-weeks' -old  babe  who 
was  killed  by  thirty  drops  of  undiluted  creolin,  the  chief  symptom  being  those  of 
violent  irritation  of  the  mouth  and  upper  respiratory  and  digestive  tracts.  Death 
occurred  chiefly  through  inflammation  of  the  glottis. 

Eisenberg  asserts  that  a  three  per  cent,  solution  of  creolin  will  kill  anthrax 
spores  in  forty-eight  hours,  but  on  the  other  hand  both  Esmark  and  Van  Ermen- 
gen '  failed  to  kill  the  anthrax  spores  with  a  ten  per  cent,  solution  after  exposure 
for  thirteen  days.  According  to  Burgess,  a  twenty  per  cent,  solution  of  creolin 
destroyed  the  bacillus  coli  communis  in  five  minutes,  being  equivalent  to  2.5  per 
cent,  solution  of  carbolic  acid. 

CRESOL  SALICYLATE,  or  Cresalol,  is  affirmed  by  Nencki  to  undergo  decompo- 
sition in  the  intestines,  yielding  cresol  and  salicylic  acid.  It  is  said  to  act  very 
much  as  does  salol,  but  to  be  less  poisonous  on  account  of  the  great  insolubility 
of  cresol.  Dose,  five  to  ten  grains. 

SODII  PHENOL  SULPHONAS.  U.  S. — Both  the  sodium  and  zinc  salts  of  sulpho- 
carbolic  acid  are  official  in  the  U.  S.  Pharmacopoeia.  The  sulphocarbolates  were 
introduced  some  years  ago  as  intestinal  antiseptics,  for  which  purpose  it  was 
evidently  expected  they  would  possess  the  antiseptic  virtues  of  carbolic  acid  and  the 
innocuousness  of  the  sulphocarbolates.  It  has  been  shown,  however,  by  Withers 
that  they  are  not  possessed  of  any  direct  antiseptic  power.  More  recently  it  has 
been  claimed  for  them  that  they  are  decomposed  in  the  intestinal  tract  with  the 
liberation  of  carbolic  acid,  but  we  know  of  no  experimental  or  scientific  evidence 
tending  to  show  the  truth  of  this  belief,  and  their  value  is  extremely  doubtful. 

NAPHTALENUM— NAPHTALIN.     U.  S. 

Naphtalin  is  a  hydrocarbon  obtained  by  the  fractional  distillation  of 
coal-tar,  or  sometimes  by  the  dry  distillation  of  organic  bodies.  It  is 
a  white,  shining,  crystalline  substance,  fusible  at  176°  F. ,  insoluble  in 
water,  but  soluble  in  alcohol,  chloroform,  and  ether.  It  is  poisonous  to 
the  lower  forms  of  life,  and  under  the  name  of  tar  camphor  has  largely 

54 


85o  EXTRANEOUS    REMEDIES. 

supplanted  true  camphor  as  a  means  of  preventing  the  deposition  by 
moths  of  eggs  in  woollen  clothing,  and  the  destruction  by  insects  in 
natural  history  museums,  etc.  In  internal  medicine  it  was  some  years 
ago  brought  forward  by  Dupasquier  as  an  expectorant  especially  valuable 
in  chronic  bronchitis  with  a  large  amount  of  secretion.  It  has  also  been 
used  with  asserted  excellent  results  as  a  t&niacidc,  and  as  a  vermifuge  in 
cases  of  seat-worms,  when  it  should  be  given  by  injection,  from  fifteen 
grains  to  half  a  drachm  in  two  or  three  ounces  of  olive  oil.  First  em- 
ployed by  Rossbach,  of  Jena,  in  intestinal  catarrh,  it  has  been  largely 
given  in  all  forms  of  intestinal  inflammation  and  in  typhoid  fever.  It  has 
also  been  used  externally  as  an  antiseptic  dressing,  and  as  a  local  appli- 
cation in  various  skin  diseases.  It  has  certainly  proved  effective  in  many 
cases,  but  has  been  supplanted  by  napthol,  which  is  similar  to  it  in  action 
and  probably  more  effective.  The  ordinary  dose  is  from  two  to  eight 
grains  (0.12-0.5  Gm.),  but  as  much  as  eighty  grains  (5.5  Gm. )  per  day 
are  said  to  have  been  given  with  good  results.  It  is  best  administered 
as  a  powder  in  capsules. 

BETA-NAPHTOL— NAPHTOL.     U.  S. 

Naphtol  is  a  phenol  which  is  present  in  small  quantities  in  coal-tar, 
but  is  usually  prepared  artificially  by  heating  naphtalin  with  sulphuric 
acid  and  fusing  the  resulting  naphtalin-sulphonic  acids  with  alkaline 
hydrates.  There  are  two  naphtols,  alpha  and  beta,  of  which  beta- 
naphtol  is  official.  It  occurs  as  colorless  or  pale  buff  crystalline  laminae, 
or  as  a  white  or  yellowish-white  crystalline  powder,  of  a  pungent  but 
not  persistent  taste,  and  a  faint  odor  suggesting  carbolic  acid.  It  is 
permanent  in  the  air,  very  slightly  soluble  in  water,  very  freely  soluble 
in  alcohol. 

THERAPEUTICS. — Beta-naphtol  was  introduced  by  Bouchard  and 
Maximovitch  into  practical  medicine  as  a  germicide  which  might  be  used 
on  or  within  the  human  body  for  the  purpose  of  inhibiting  the  growth  of 
disease-germs.  It  appears  to  be  of  only  second  rank  as  a  germicide,  but 
to  have  value  on  account  of  being  nearly  free  from  toxic  powers  in 
relation  to  the  higher  animals. 

Experimenters  are  somewhat  at  variance  in  regard  to  the  exact  germicidal 
power  of  beta-naphtol.  According  to  Bouchard  and  Maximovitch,  in  the  labora- 
tory i  to  3000  will  kill  some  pathogenetic  germs  and  greatly  retard  the  growth  of 
the  bacilli  of  typhoid  fever  and  of  tuberculosis,  whilst  about  three  grains  per  quart 
will  arrest  putrefaction.  The  experiments  of  Surveyor  and  Harley,1  however,  in- 
dicate that  naphtol  is  less  active  as  a  germicide  than  is  bismuth  subnitrate.  Bou- 
chard and  Maximovitch,  in  contrasting  experiments,  found  that  mercuric  iodide  is 
six  times  more  antiseptic  than  beta-naphtol,  but  that  carbolic  acid  is  five  times  less 
antiseptic,  and  creosote  four  times  less  antiseptic.  Weeks  found  that  i :  10  solution 
of  beta-naphtol  in  ether  destroyed  the  staphylococcus  pyogenes  in  thirty  seconds. 
The  toxic  dose  of  beta-naphtol  was  found  to  be  3.8  grains  per  kilo  of  the  ani- 
mal, making  it  two  hundred  and  fifty-three  times  less  poisonous  than  mercuric 


DISINFECTANTS.  851 

iodide.  At  this  rate  the  poisonous  dose  for  an  ordinary  man  would  be  between 
three  and  four  thousand  grains.  In  the  animals  killed  by  it,  death  took  place 
through  an  arrest  of  respiration,  the  heart  retaining  its  activity. 

In  experiments  made  to  determine  whether  digestion  would  be  seri- 
ously interfered  with  by  beta-naphtol,  Clarke  found  that  it  has  a  very  dis- 
tinct retarding  influence  on  the  artificial  digestion  of  egg  albumin  by 
peptic  fluids,  a  very  slight  effect  on  the  artificial  digestion  of  milk  by  the 
same,  and  no  effect  at  all  on  pancreatic  digestion  of  milk  or  albumin, 
nor  on  the  conversion  of  starch  into  sugar. 

Externally,  beta-naphtol  was  first  used  in  1881  by  Kaposi,  of  Vienna, 
who  found  it  to  be,  when  in  solution  in  oil  or  alcohol,  markedly  irritating 
to  the  skin,  i  part  to  100  distinctly  affecting  eczematotis  eruptions,  and 
i  to  \\  parts  per  100  being  sufficient  to  provoke  urticaria  on  a  healthy 
skin.  In  the  form  of  soap,  containing  2  parts  per  100,  Kaposi  found  it 
useful  in  prurigo,  ichthyosis,  herpes,  andfavus,  obtaining  in  many  cases 
the  best  results  by  alternating  this  soap  with  a  sulphur  soap,  and  avoid- 
ing in  this  way  a  cumulation  in  the  system  which  he  believed  was  pos- 
sible by  the  absorption  of  the  drug.  The  practice  of  Kaposi  was  followed 
by  numerous  dermatologists  with  success,  and  led  to  the  use  of  the  rem- 
edy locally  in  inflammation  of  the  mucous  membranes,  such  as  conjunc- 
tivitis, chronic  laryngitis,  otitis,  etc. 

Bouchard  introduced  the  internal  use  of  the  drug  for  the  purposes  of 
disinfecting  pathological  cavities,  and  for  intestinal  antisepsis,  especially 
in  typhoid  fever.  Following  Bouchard,  a  large  number  of  clinicians  have 
reported  excellent  results  from  the  administration  of  the  drug  in  typhoid 
fever ;  it  is  affirmed  that  it  lessens  the  diarrhoea  and  other  local  abdomi- 
nal symptoms  both  in  adults  and  children.  The  remedy  has  also  come  into 
use  in  cases  of  dilatation  of  the  stomach,  intestinal  dyspepsia,  diarrhoea, 
or  dysentery,  when  it  is  desired  to  check  fermentative  changes  in  the  ali- 
mentary canal  without  producing  the  astringent  or  sedative  effects  of 
bismuth  salts.  The  slow  injection  into  the  trachea,  drop  by  drop,  dur- 
ing a  half-hour,  of  two  hundred  to  three  hundred  cubic  centimetres  of  its 
solution  (i  to  1000)  is  affirmed  by  Pignol  to  be  a  useful  procedure  in 
pneumonia.  Teissier  has  given  it  intravenously  ;  others  have  exhibited 
it  by  the  mouth  in  epidemic  influenza  and  low  fevers  for  the  relief  of 
albuminuria  ;  but  these  uses  of  it  are  of  doubtful  value.  Larger  doses 
than  from  three  to  four  grains  (0.20-0.25  Gm. ),  given  in  capsules  every 
two  hours,  are  apt  to  disturb  the  stomach. 

The  following  formulae  may  be  used  in  making  solutions  for  local  use  :  i. 
Weak  solution,  for  parts  in  which  mucous  membranes  are  exposed :  naphtol,  5 
grammes  ;  alcohol  at 60°  F.,  I  litre.  2.  Ordinary  solution:  naphtol,  15  grammes  ; 
alcohol  at  60°  F.,  i  litre.  3.  Strong  solution,  for  touching  diseased  portions  of  the 
skin,  or  septic  excoriations  :  naphtol,  15  to  500  grammes  per  litre.  Solutions  for 
inierstitialinjections,  or  closed  septic  cavities :  naphtol,  5  grammes  ;  alcohol  at  90° 
F.,  33  grammes  ;  hot  distilled  water,  to  make  100  cubic  centimetres  ;  filter,  and  use 
warm.  A  few  drops  may  be  injected  into  indurated  glands  or  abscesses. 


852  EXTRANEOUS    REMEDIES. 

BETOL  of  Sahli,1  or  Naphthalol  of  Robert,  is  ft-naphtol  ether  salicylate,  and 
occurs  in  small,  white,  resplendent,  almost  tasteless  crystals,  insoluble  in  water.  It 
is  a  compound  analogous  to  salol,  but  having  the  base  of  naphtol  instead  of  phenol, 
and  yielding,  in  the  intestinal  juices,  salicylic  acid  and  naphtol.  It  contains  ten  per 
cent,  less  salicylic  acid  than  does  salol,  and  is  of  no  value  in  rheumatism,  but  has 
been  much  used  as  an  intestinal  antiseptic,  and  has  been  highly  recommended  by 
Robert  in  gonorrhoea  and  other  forms  of  cystitis.  Dose,  five  to  fifteen  grains. 

MENTHOL,  U.  S. ,  or  Oil  of  Peppermint  Camphor,  has  obtained  great 
notoriety  as  a  local  anaesthetic,  and,  if  freely  rubbed  upon  a  part,  it 
undoubtedly  will  often  relieve  neuralgic  pains  when  they  are  superficial 
and  peripheral  in  their  origin  :  its  solution  (2  to  10  grs. — f§i  water)  is 
said  also  to  be  very  effective  in  pruritus  ani,  chronic  painful  eczemas, 
urticaria,  etc.  Its  physiological  action  has  been  studied  by  Paolo  Pella- 
cani.1  In  the  frog  it  causes  paralysis,  first  of  the  spinal-centres  and  finally 
of  the  nerve-trunks.  In  the  mammal  both  mobility  and  sensibility  are 
depressed,  the  animal  grows  cold,  and  the  respiration  becomes  slow  and 
shallow.  Small  doses  excite,  larger  paralyze  the  frog's  heart.  In  the 
poisoned  mammal  there  were  very  curious,  unexplained  rhythms  of  rise 
and  fall  of  the  blood-pressure. 

Goldscheider  *  has  been  led  to  the  conclusion  that  the  sensation  of  cold  pro- 
duced by  the  local  application  of  menthol  is  due  to  a  special  influence  exerted  upon 
the  special  nerves  of  temperature  by  finding, — first,  that  after  the  application  of  a 
solution  of  menthol  in  lanolin  the  local  temperature  is  increased  2°  C.,  although  a 
marked  sensation  of  cold  has  been  produced  ;  and,  secondly,  that  the  cold  is  not 
due  to  evaporation,  because  covering  the  part  to  which  the  menthol  is  applied  with 
a  watch-glass  does  not  affect  the  sensation.  He  also  found  that  if  the  menthol 
ointment  were  applied  to  one  side  of  the  forehead,  bodies  which  previously  had 
caused  the  sensation  of  cold  no  longer  did  so,  and  that  application  of  menthol 
produced  a  sensation  of  warmth  upon  the  elbow  and  the  volar  side  of  the  wrist, 
positions  at  which,  according  to  Herzen,  similar  warm  sensations  are  caused  by 
pressure  upon  the  nerve-trunks.  I.  loteyko  *  found  that  the  sensation  of  cold  is 
preceded  by  loss  of  general  sensibility,  and  that  the  maximum  of  cold  and 
anaesthesia  correspond. 

S.  A.  Russell 3  affirms  that  menthol  has  a  remarkable  power  of  con- 
trolling superficial  inflammations.  He  asserts  that  an  ethereal  solution, 
of  the  strength  of  from  ten  to  fifty  per  cent. ,  two  or  three  times  a  day  by 
means  of  a  camel' s-hair  pencil,  will  control  boils,  carbuncles,  superficial 
abscesses,  etc.  It  is  very  largely  employed,  in  conjunction  with  camphor, 
as  a  local  application  in  rhinitis  and  laryngitis.  Bishop5  recommends 
a  solution  containing  ten  per  cent,  of  each  drug  ;  more  commonly  a  one 
to  two  per  cent,  solution  in  liquid  petrolatum  is  used  by  atomization. 

THYMOL.     U.  S. 

Thymol  is  found  in  the  oil  of  thyme*  and  of  some  other  plants.  It 
occurs  either  as  an  uncrystallizable  liquid  or  in  white  rhombic  or  acicular 

*According  to  Cardeac  and  Meunier  (Journ.  Med.  lret.  Zootech.,  1890),  the  physio- 
logical actions  of  the  oils  of  Thymus  serpyllum  and  Thymus  vulgaris  are  the  same ; 


DISINFECTANTS.  853 

crystals.  It  has  been  urged  as  a  substitute  for  carbolic  acid  by  Volkmann 
and  Ranke,  of  Halle,  but,  although  a  powerful  antiseptic,  has  not  come 
largely  into  vogue.  Its  fragrant  odor  has  proved  a  decided  disadvantage, 
in  summer  at  least,  by  attracting  swarms  of  flies.  It  is  not  free  from  poi- 
sonous properties. 

Spencer  Wells  employs  its  watery  solution  (i  :  1000  of  warm  water);  Volk- 
mann, thymol  one  part,  glycerin  twenty  parts,  alcohol  ten  parts,  water  one  thousand 
parts.  According  to  Steinberg  a  one-fourth  per  cent,  solution  of  thymol  in  alcohol 
is  equivalent  in  germicidal  properties  to  one  and  one-fourth  per  cent,  solution  of 
carbolic  acid  against  the  coccus  of  mouth  septicaemia.  Bucholz 6  ranks  thymol  as 
about  the  same  strength  as  salicylic  acid.  It  has  been  used  internally  by  Balz  *  in 
doses  of  thirty  grains  a  day,  or  less.  In  a  few  instances  nausea  and  vomiting  were 
caused.  There  were  abundant  sweating,  singing  in  the  ears,  deafness,  constriction 
in  the  forehead,  reduction  of  temperature,  and  frequently  diarrhoea.  The  urine 
was  dark  greenish,  yellowish-brown  by  transmitted  light,  free  from  albumin, 
becoming  cloudy  and  grayish-white  on  the  addition  of  the  tincture  of  the  chloride 
of  iron.  Violent  delirium  occurred  several  times,  also  marked  collapse,  and,  in 
one  case  of  typhoid  fever,  unconsciousness,  with  most  alarming  collapse.  Balz 
concludes  that  the  remedy  is  much  less  certain  and  more  dangerous  as  an  antipy- 
retic than  is  salicylic  acid. 

The  possession  of  poisonous  properties  by  thymol  has  been  confirmed  by  the 
recent  experiments  of  B.  Kiissner.*  This  observer  found  that  when  given  to  dogs 
and  rabbits  by  the  stomach  the  poison  acts  very  slowly  and  feebly,  on  account  of 
its  slow  absortion,  but  when  injected  into  the  circulation  it  produces  death  by 
failure  of  respiration.  Coma  is  developed  some  time  before  death,  and  the  blood- 
pressure,  which  at  first  maintains  itself,  falls  steadily.  Post-mortem  examination 
failed  to  detect  fatty  degeneration  or  other  lesion  in  either  the  solid  tissues  or 
the  blood.  The  continuous  repeated  exhibition  of  small  doses  of  thymol  had  no 
perceptible  effect,  except  to  interfere  in  some  way  with  nutrition,  so  that  the 
animals  lost  'flesh.  Kiisner  has  found  that  thymol  has  the  power  of  dissolving  the 
red  blood-corpuscles.* 

Thymol  is  eliminated  through  the  kidneys  partly  as  thymol  itself,  partly  as 
thymo-hydrochinone  united  with  sulphuric  acid,  partly  as  a  chromogen,  which  is 
probably  an  oxidation  product  of  thymol,  and  partly  as  some  acid  of  unknown 
constitution  (F.  Blum*). 

Thymol  on  account  of  its  agreeable  taste  is  largely  employed  as  an 
antiseptic  in  diseased  conditions  of  the  mouth  and  throat.  It  is  no  longer 
used  in  diabetes  as  suggested  by  Kiissner  ;  f  nor  as  an  intestinal  antiseptic 
in  typhoid  fever  as  recommended  by  Martime  and  by  F.  P.  Henry.*  It 
has  been  recommended  by  Fischer 7  and  others  in  pertussis.  Thymol  is 
also  employed  as  an  anthelmintic  (see  p.  811).  Dose,  fifteen  to  twenty 
grains  (1-1.3  Gm. )  in  the  twenty -four  hours. 

Thymacetin  is  a  white  crystalline  powder,  very  slightly  soluble  in  water,  which 
has  the  same  chemical  relation  to  thymol  that  phenacetin  has  to  phenol.  Accord- 

they  produce  in  animals  dilated  pupils,  staggering  gait,  hallucinations,  loss  of  sensibility, 
muscular  relaxation,  insomnia,  trembling,  contractures,  exceedingly  rapid  respiration, 
and  death,  preceded  by  complete  muscular  relaxation  and  anaesthesia. 

*See  Hoffmann  und  Schwalbe's  Jahresb.,  1879,  208. 

fSee  Fiirbringer  (Deutsches  Archivf.  Klin.  Med.,  xxi.) 


854  EXTRANEOUS    REMEDIES. 

ing  to  Solly,5  it  is  a  valuable  analgesic  in  neurotic  pains  and  is  also  soporific.     Dose, 
five  to  fifteen  grains  (0.3-1  Gm.)(  in  capsule. 

RESORCINOI — RESORCIN.*     U.  S. 

Resorcin,  pyrocatechin  and  hydroqiiinone ,  three  dioxybenzols,  resem- 
ble each  other  very  closely  in  physiological  effects,  but  of  which  only 
resorcin  is  used  in  medicine.  It  occurs  in  colorless,  short,  aromatic  prisms 
or  plates  of  an  unpleasantly  sweet,  somewhat  acrid  taste,  which  on  exposure 
to  the  air  becomes  reddish.  It  is  freely  soluble,  at  59°  F. ,  in  0.6  part  of 
water,  in  alcohol,  in  ether,  and  in  about  twenty  parts  of  fixed  oil. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Elimination. — Resorcin  is 
an  active  irritant,  but  is  scarcely  able  to  act  as  an  escharotic.  According 
to  Joseph  Schomacker,1  it  is  eliminated  with  the  urine  as  a  sulpho-acid, 
which  on  boiling  with  HC1  is  decomposed,  resorcin  being  set  free  ;  after 
very  large  doses,  free  resorcin  may  be  found  in  the  urine.  The  excretion 
is  said  to  be  completed  in  about  seven  hours.  It  is  actively  poisonous 
to  the  lower  organisms,  and,  according  to  Martin  Cohn'2  and  Andeer,3 
a  one  per  cent,  solution  of  it  is  sufficient  to  arrest  for  a  long  time  putre- 
factive changes  in  the  urine,  organic  infusions,  and  even  animal  tissues. 
Platt 4  states,  however,  that  it  is  distinctly  inferior  to  carbolic  acid  as  an 
antiseptic. 

General  Effects. — In  doses  of  twenty  to  forty  grains  resorcin  causes 
flushing  of  the  face,  with  giddiness,  buzzing  in  the  ears,  and  some  quick- 
ening of  the  breathing  and  pulse,  followed,  after  a  time,  by  violent  per- 
spiration and  sometimes  depression  of  temperature.  Sixty  grains  caused 
in  man  giddiness  and  violent  perspiration,  with  marked  anxiety,  ending 
in  collapse  and  unconsciousness. 

Andeer  took  about  one  hundred  and  fifty  grains  of  resorcin,  dissolved  in  a 
pint  of  water,  during  fifteen  minutes.  After  disturbance  of  the  cerebration  and  of 
the  special  senses,  he  fell  into  a  condition  of  collapse,  with  cold  extremities,  epilep- 
tiform  convulsions  with  loss  of  consciousness,  opisthotonos,  and  marked  disturb- 
ance of  the  respiration.  Consciousness  did  not  return  for  five  hours.  Murrell5 
records  a  case  in  which  a  woman  took  one  hundred  and  twenty  grains  of  resorcin, 
and  immediately  felt  giddy,  had  sensation  of  pins  and  needles  all  over  her,  and  a 
few  minutes  later  was  insensible,  with  closed  eyes,  clenched  hands,  pallid,  blanched 
lips,  dry  tongue,  normal  pupils,  and  insensible  conjunctiva  ;  the  temperature  was 
94°  F. ;  the  reflexes  were  entirely  gone  ;  the  pulse  was  weak  and  thready.  Jos. 
Loeffier6  reports  the  case  of  a  woman,  thirty-one  years  old,  who,  immediately  after 
the  injection  into  the  stomach  of  two  litres  of  a  three  per  cent,  solution  of  resorcin, 
was  seized  with  violent  gastric  pain,  followed  at  once  by  unconsciousness,  cyanotic 
face,  and  clonic  contractions.  In  spite  of  the  immediate  removal,  as  far  as  possible, 
of  the  solution,  the  cyanosis  became  more  intense,  the  unconsciousness  and  mus- 
cular relaxation  complete,  with,  from  time  to  time,  active  tremors  ;  the  pulse  very 
small  and  frequent  ;  the  respiration  completely  arrested,  with  respiratory  muscles 

*  Thioresorcin  is  a  sulphur  substitution-product  from  resorcin.  A  case  of  poisoning 
by  its  external  use  is  reported  by  H.  Amon  (Munch.  Med.  Wochenschr.,  1889,  xxxvi.). 
The  most  peculiar  symptom  was  erythematous  oedema  of  the  face,  and  general  eruption 
somewhat  similar  to  that  of  measles,  with  intense  itching. 


DISINFECTANTS.  855 

in  such  a  condition  of  tetanus  as  greatly  to  embarrass  artificial  respiration.  Under 
the  continued  use  of  artificial  respiration,  however,  recovery  was  finally  secured. 
In  several  cases  of  children  the  washing  out  of  the  stomach  with  a  three  per  cent, 
solution  has  been  followed  by  collapse  and  death,  and  in  one  case  haemoglobin  was 
found  in  the  urine. 

In  the  lower  animals  (Dujardin-Beaumetz7)  resorcin  causes  tremors,  loss  of 
consciousness,  and  epileptiform  convulsions,  which,  when  the  dose  has  been  suffi- 
ciently large,  become  more  and  more  violent,  until  the  increasing  disturbance  of 
breathing  ends  in  respiratory  arrest.  During  the  spasms  the  temperature  of  the 
animal  is  distinctly  elevated,  but  when  there  is  quiet  narcosis  it  may  fall  below 
normal.  The  urine  becomes  olive-green,  deepening  into  blackish. 

Resorcin  resembles  carbolic  acid  in  being  a  universal  poison,  but  is 
less  active.  It  probably  affects  the  nerve-centres  as  does  carbolic  acid, 
and  has  been  shown  by  Beyer  to  be  a  direct  cardiac  paralyzant. 

THERAPEUTICS. — On  account  of  its  being  less  efficient  and  more  dan- 
gerous than  other  members  of  its  class,  resorcin  is  used  solely  as  a  valu- 
able topical  remedy  in  diseases  of  the  skin  and  mucous  membranes.  It 
has  been  highly  recommended  by  Hoefer,  Lichtheim,  Janicke,  Fliesburg, 
Baginsky,*  and  others  in  various  acute  and  subacute  gastric  or  intestinal 
inflammations,  such  as  enteritis,  gastric  ulcer,  and  cholera  infantum,  but 
in  our  experience  has  not  given  satisfaction.  In  hay  fever,  chronic  otitis, 
gonorrhcea,  leucorrhaa,  and  other  mucous  catarrhs,  it  may  be  applied 
locally  in  the  solution  of  from  one  to  fifteen  per  cent.  The  three  to  five 
per  cent,  solution  has  been  largely  used  in  Germany  in  washing  out 
diseased  stomachs,  but  care  is  necessary  to  avoid  poisoning.  In  chronic 
cystitis  irrigation  of  the  bladder  with  a  three  per  cent,  solution  has  been 
found  effective. 

It  is  said  to  be  valuable  in  the  treatment  of  the  various  parasitic  skin 
diseases  such  as  tinea  and  scabies.  Too  irritating  for  acute  inflammations 
of  the  skin,  it  certainly  exerts  a  powerful  effect  on  recent  cell  infiltrations, 
and  is  extraordinarily  successful  in  chronic  and  subacute  eczema,  where 
there  is  much  thickening  from  exudation,  in  seborrhoea,  and  even  in 
psoriasis  and  pityriasis.  It  is  preferably  used  in  solution  ;  from  ten  to 
thirty  grains  in  one  drachm  of  alcohol,  one  drachm  of  glycerin,  and 
eight  drachms  of  water,  well  sopped  on  the  part  and  allowed  to  dry. 
According  to  Andeer,  resorcin,  in  powder  or  in  saturated  ethereal  solu- 
tion, is  a  feeble  caustic,  useful  in  the  treatment  of  chancres,  of  papilloma, 
and  even  of  epithelioma  and  diphtheria.  Dose,  two  to  five  grains 
(0.13-0.3  Gm. ). 

FORMALDEHYDE. 

Formaldehyde,  formyl  or  for  mol,  is  a  gaseous  body  which  is  obtained 
by  the  oxidation  of  methylic  alcohol  at  moderately  high  temperature, 
as  by  passing  the  vapors  over  red-hot  metal  or  carbon.  It  readily  dis- 
solves in  water  and  alcohol,  forming  a  colorless  fluid,  having  a  peculiar 
odor  and  an  exceedingly  bad  taste. 

•See  TTierap.  Gaz.,  ii.  and  iii.  and  Berliner  Klinisc he  Wochen.,  1889,  xxvi. 


EXTRANEOUS    REMEDIES. 

Formalin  is  a  forty  per  cent,  aqueous  solution  of  formaldehyde,  pro- 
tected by  a  trade-mark  name.  The  fifty  per  cent  solution  would  be  more 
convenient,  but  undergoes  decomposition  and  becomes  turbid  upon  stand- 
ing. The  physician  should  order  LIQUOR  FORMALDEHYDE,  U.  S., 
Solution  of  Formaldehyde,  which  contains  ' '  not  less  than  thirty-seven  per 
cent,  by  weight  of  absolute  formaldehyde. "  —  U.  S.  P. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Absorption  and  Elimina- 
tion.— Formaldehyde  is  an  intensely  active  local  irritant,  producing  even 
when  in  very  minute  amount  in  the  air  violent  irritation  of  the  respira- 
tory mucous  membrane,  or,  it  may  be,  fatal  pulmonary  inflammation. 
It  is  a  powerful  germicide.*  It  is  also  a  very  active  coagulant  of  albu- 
min and  gelatin  when  in  at  all  concentrated  form;  and  when  added  to 
blood  it  causes  an  immediate  coagulation,  with  a  serum  so  strongly 
colored  red  as  to  suggest  destruction  of  the  red  blood-corpuscles,  though 
it  may  be  that  the  color  is  due  simply  to  the  squeezing  out  of  the  corpus- 
cles from  the  clot.  According  to  Mosso  and  Paoletti,1  however,  when 
added  in  a  very  dilute  form  to  an  albuminous  solution,  formaldehyde  not 
only  does  not  coagulate  the  albumin,  but  so  acts  as  to  prevent  the  coagu- 
lation of  albumin  by  heat.  It  is  therefore  capable  of  absorption,  and  the 
statements  made  that  the  urine  passed  by  animals  to  which  it  is  given 
even  in  moderate  quantities  is  incapable  of  putrefaction  indicate  that  it  is 
not  only  absorbed,  but  also  eliminated  unchanged  from  the  kidneys. 

General  Effects.  — The  violent  irritation  produced  by  formaldehyde  is 
so  immediate  that  accidental  or  purposive  poisoning  by  it  is  very  rare. 
The  general  action  of  the  drug  is  evidently  feeble,  it  producing  more 
serious  symptoms  when  given  by  the  mouth  than  when  injected  hypoder- 
mically  (Mosso  and  Paoletti). 

Trillat  *  states  that  sixty-six  centigrammes  of  formalin  per  kilogramme  given  to 
the  guinea-pig  are  not  mortal,  although  the  urine  passed  by  the  animal  is  incapable 
of  putrefaction  ;  whilst  the  intravenous  injection  of  thirty-eight  centigrammes  per 
kilogramme  causes  in  the  rabbit  no  pronounced  symptoms.  According  to  Mosso 
and  Paoletti,  fifty  cubic  centigrammes  per  kilogramme  injected  hypodermically  pro- 
duce in  the  dog  severe  poisoning,  with  fall  of  temperature,  ending  after  many  days 
in  death  ;  the  same  amount  given  by  the  stomach  causes  in  the  dog  violent  con- 
vulsions, general  rigidity,  salivation,  and  in  a  short  time  death,  preceded  by  stupor 
and  unconsciousness. 

In  J.  Kluber's*  case  of  poisoning  the  patient,  a  man,  was  found  unconscious 
and  supposed  to  be  suffering  from  apoplexy.  The  coma  lasted  for  many  hours, 
going  off  gradually  in  a  stupor.  The  urine  was  suppressed  for  nineteen  hours,  and 
formic  acid,  but  neither  sugar  nor  albumin,  was  found  in  it  L.  Zorn  *  reports  a 
case  with  burning  in  the  mouth  and  stomach,  nausea,  mild  cyanosis,  albuminuria, 
and  difficulty  of  breathing. 

According  to  Mosso  and  Paoletti,  small  doses  cause  rise  in  the  blood- 
pressure,  probably  as  the  result  of  peripheral  contractions  of  the  arteries; 

*  Formaldehyde  also  has  a  very  powerful  influence  on  various  forms  of  organic 
matter ;  i  part  in  4000  completely  decolorizes  wine,  precipitating  extractive  and  coloring 
matter. 


DISINFECTANTS.  857 

whilst  toxic  doses  depress  the  circulation  and  so  act  upon  the  blood  that 
on  exposure  it  coagulates  instantly,  with  the  separation  of  a  dark  red 
serum. 

The  discovery  by  Trillat,  in  1888,  that  formaldehyde  is  a  powerful 
germicide,  has  been  abundantly  confirmed,  but  its  activity  has  been  greatly 
overestimated.  The  more  recent  investigations  show  that  it  is  not  much 
stronger  than  is  carbolic  acid. 

According  to  Burgess,  a  two  per  cent  solution  of  formaldehyde  kill  the 
bacillus  coli  communis  in  five  minutes.  In  the  experiments  of  Slater  and  Rideal 5 
it  required  fifty  minutes  for  a  one  per  cent,  solution  to  kill  the  staphylococcus 
pyogenes  aureus  or  bacillus  typhosus,  and  thirty  minutes  to  destroy  the  bacillus  coli 
communis.  Clothing  soaked  twenty-four  hours  in  a  i  :  1000  solution  was  not  always 
sterile,  but  after  being  exposed  to  a  one  per  cent  solution  was  always  sterilized. 

As  regards  the  effect  of  the  formaldehyde  vapor  in  disinfecting  a  room,  Slater 
and  Rideal  found  that  after  the  evaporation  of  one  and  one-half  ounces  of  a  forty  per 
cent,  formaldehyde  solution  in  a  room  of  fifteen  hundred  cubic  feet  there  was  a 
marked  diminution  of  the  number  of  organisms  found  in  the  dust,  although  they 
were  not  all  destroyed.  According  to  Trillat,  one  pound  of  a  forty  per  cent  for- 
maldehyde solution  is  sufficient  to  disinfect  an  ordinary-sized  room.  Kenwood  has 
determined  that  when  formaldehyde  vapor  is  present  in  the  air  in  the  proportion  of  one 
and  one-half  to  two  per  cent,  there  is  complete  and  rapid  disinfection  of  all  the  sur- 
faces. Woodhead  found  that  the  vaporization  of  one  pound  of  forty  per  cent  formal- 
dehyde solution,  by  means  of  a  special  form  of  apparatus,  destroyed  all  exposed 
cultures,  including  the  spores  of  the  anthrax  bacillus,  but  that  pieces  of  folded  linen 
were  not  always  completely  sterile.  In  a  lamp  generating  formaldehyde  directly 
from  methyl  alcohol,  according  to  Kenwood,  it  requires  one  and  one-half  litres  of 
alcohol  to  disinfect  a  room  of  two  thousand  cubic  feet  A  popular  and  con- 
venient form  of  formaldehyde  generation  is  through  the  heating  of  tablets  of  para- 
formaldehydf.  According  to  Rideal,  one  gramme  per  thousand  cubic  feet  of  para- 
form  did  not  kill  the  bacillus  coli  communis  in  four  hours.  Four  grammes  per 
thousand  cubic  feet  of  air  space  killed  the  test-germs  which  were  exposed  on  silk 
threads,  but  not  cultures  soaked  into  paper  slips.  Ten  grammes  of  paraform  per 
one  thousand  cubic  feet  killed  various  non-sporing  micro-organisms,  both  exposed 
and  when  wrapped  inside  of  rolls  of  linen.  The  spores  of  the  anthrax  bacillus  and 
bacillus  subtilis  were  usually  but  not  invariably  destroyed  by  twenty  grammes  per 
thousand  cubic  feet. 

In  an  elaborate  investigation  made  in  1903  by  Ravenel  and  Gilliland  •  the  value 
of  formaldehyde  as  a  germicide  was  abundantly  reaffirmed,  and  the  importance  of 
the  abundance  of  moisture  in  the  air  with  the  formaldehyde  vapor,  and  the  value  of 
high  temperature  when  it  can  be  obtained  as  assisting  in  the  action  of  formaldehyde, 
were  made  very  apparent.  The  theory  of  Van't  Hoff,  that  formaldehyde  acts  as  a 
bactericide  by  the  formation  of  an  active  oxygen,  has  been  disproven  by  Waldemar 
Koch,'  and  it  would  appear  that  it  acts  directly. 

According  to  the  experiments  of  Aronson  and  of  Burkhard,7  formaldehyde  not 
only  is  a  germicide,  but  also  has  the  power  of  destroying  the  toxins  of  diphtheria,  of 
tetanus,  and  probably  of  other  diseases. 

THERAPEUTICS. — On  account  of  the  safety  connected  with  its  use,  its 
activity,  its  permanence  of  constitution,  and  its  lack  of  destructive  action 
on  vegetable  and  animal  substances,  formaldehyde  is  probably  the  most 
reliable  and  the  most  generally  useful  of  all  the  germicides  when  it  is  not 


858  EXTRANEOUS    REMEDIES. 

necessary  to  bring  the  agent  in  contact  with  the  human  body.  It  does 
not  affect  either  the  color  or  structure  of  clothing  or  other  materials  in 
common  use.  Its  vapor,  being  of  low  specific  gravity,  mixes  readily  with 
the  air,  and  penetrates  loose  fabrics  much  more  deeply  than  does  any 
other  known  germicide. 

Using  an  apparatus  invented  by  himself  for  the  production  of  formaldehyde 
directly  from  methylic  alcohol,  Trillat  found  that  it  was  possible  completely  to  dis- 
infect rooms  and  the  furniture  contained  therein  in  six  hours,  by  the  consumption 
of  from  four  to  six  litres  of  the  alcohol  for  each  three  hundred  cubic  metres  of  the 
room.  In  1895  Van  Ermengen  and  E.  Sugg10  sterilized  in  a  room  books  and  other 
small  objects  containing  the  germs  of  diphtheria,  tuberculosis,  scarlet  fever,  small- 
pox, etc.,  by  means  of  formaldehyde  evaporated  from  its  watery  solution  in  such 
quantity  that  there  was  about  the  value  of  five  cubic  centimetres  of  formaldehyde 
in  one  litre  of  air,  and  in  1896  it  was  demonstrated  by  E.  G.  Horton11  that  infected 
books  shut  up  in  a  closed  space  could  be  disinfected  in  fifteen  minutes  by  the  vapor 
of  commercial  formalin, — one  cubic  centimetre  of  the  formalin  to  three  hundred 
cubic  centimetres  or  less  of  air, — and  that  the  books  were  not  in  any  way  injured  by 
the  process.  More  recently  there  has  been  abundant  confirmation  as  to  the  activity 
of  formaldehyde,  which,  when  properly  used  in  a  room  with  moistened  air,  fails  only 
when  the  objects  are  so  dense  or  in  such  mass  that  they  cannot  be  penetrated. 

It  has  been  shown  in  an  elaborate  series  of  experiments  by  Herzog !1 
that  the  addition  of  formaldehyde  vapor  enormously  increases  the  disin- 
fective  power  of  steam,  but  that  this  increase  of  power  does  not  influence 
the  disinfection  of  massive  objects;  the  outer  layers  of  the  object  appa- 
rently absorbing  all  the  formaldehyde  out  of  the  vapor,  so  that  inside  of 
a  bundle  of  blankets  the  effect  would  be  simply  that  of  pure  moist  heat. 
Vapor  at  70°  C. ,  containing  one  per  cent,  of  formaldehyde,  was  found  to 
kill  spores  in  four  minutes  which  were  able  to  resist  the  action  of  simple 
watery  vapor  at  98.5°  C.  for  nine  minutes  without  injury. 

In  disinfecting  an  apartment,  windows,  doors,  chimneys,  ventilators, 
and  similar  openings  should  be  tightly  closed,  whilst  the  air  should  be 
made  to  contain  at  least  one  per  cent,  of  formaldehyde  gas,  and  at  the 
end  of  twenty-four  hours,  when  the  apartment  may  be  opened,  should 
still  be  strongly  impregnated.  The  gas  may  be  obtained  by  the  pulver- 
ization of  formalin  or  other  solution  of  formaldehyde,  but  not  by  the 
simple  evaporation  of  the  solution,  since  the  formaldehyde,  upon  the  appli- 
cation of  heat,  becomes  largely  polymerized  into  a  solid,  paraform*  which 
gives  off  formaldehyde  slowly  and  in  small  quantities.  It  is  stated  that 
the  addition  of  glycerin  to  the  solution  of  formaldehyde  prevents  the 
polymerization  by  heat  of  the  formaldehyde,  so  that  the  so-called  glyco- 
formalin  (formaldehyde  thirty  parts,  water  sixty  parts,  glycerin  ten 
parts)  is  preferable  to  the  watery  solution,  although  its  use  has  the  dis- 
tinct disadvantage  of  leaving  many  articles  in  the  room  sticky  from  a 
coating  of  glycerin. 

*  Paraform,  or  polymerized  formaldehyde,  is  a  colorless,  crystalline  powder,  insolu- 
ble in  water,  of  very  stable  constitution,  which  when  heated  slowly  gives  off  formaldehyde 
gas. 


DISINFECTANTS.  859 

The  intense  activity  of  formaldehyde  as  an  irritant  greatly  interferes 
with  its  use. upon  the  human  body.  The  application  to  an  ulcerated 
surface  of  even  its  one  per  cent,  solution  causes  intense  pain  lasting  for  a 
considerable  length  of  time.  Nevertheless,  formaldehyde  is  employed  to 
a  considerable  extent  by  practical  surgeons  in  cases  of  tubercular  abscesses, 
infected  wounds,  and  infectious  inflammations  of  the  mucous  membranes. 
In  many  instances  it  is  better  to  apply  a  strong  solution  once  or  twice 
than  to  use  a  weaker  solution  more  frequently,  although  a  one  to  five 
per  cent,  solution  is  spoken  of  by  various  surgeons  as  singularly  effective. 
By  the  previous  application  of  cocaine  the  pain  normally  produced  by  the 
formaldehyde  may  be  prevented,  and  there  is  no  danger  of  systemic- 
poisoning  by  even  the  strongest  solution.  The  two  per  cent,  solution  of 
formaldehyde  is  very  effective  for  the  disinfecting  of  the  hands  of  the 
surgeon,  but  has  been  found  too  irritating  to  be  practical.  A  one  to  two 
per  cent,  solution  is  sometimes  employed  for  the  rendering  of  instruments 
aseptic,  but  its  use  is  usually  less  convenient  than  that  of  a  simple  cham- 
ber in  which  by  means  of  heated  paraform  the  instruments  may  be  disin- 
fected. It  is  stated  that  by  the  employment  of  this  apparatus  instruments 
contained  in  a  chamber  one  cubic  foot  square  may  be  absolutely  disin- 
fected in  fifteen  minutes  by  the  evaporation  of  five  grains  of  paraform  at 
a  cost  of  one  cent. 

Although  it  was  at  first  supposed  that  formaldehyde  afforded  an 
almost  ideal  substance  for  the  preservation  of  pathological  material,  ex- 
perience has  shown  that  its  usefulness  is  lessened  by  grave  difficulties. 
The  injection  of  the  cadaver  with  the  one  per  cent,  solution  usually  suf- 
fices for  preservation,  and  the  injected  body  may  be  kept  indefinitely  in  a 
solution  of  formaldehyde,  provided  it  be  not  allowed  to  float  upon  the 
top  and  become  mouldy.  The  emanations  from  such  a  cadaver  are,  how- 
ever, very  irritant,  not  only  to  the  hands,  but  also  to  the  respiratory 
mucous  membrane  of  the  dissector,  and  the  great  rigidity  produced  by 
the  formaldehyde  often  interferes  with  the  use  of  the  cadaver. 

Kaiserling's  Solution  is  highly  recommended  for  the  preservation  of  patholog- 
ica  specimens  without  change  of  color,  provided  the  specimen  in  the  solution  be 
stored  in  the  dark,  as  very  few  pigments  resist  the  chemical  influence  of  the  sun- 
rays  in  a  moist  vehicle.  The  microscopic  structure  of  the  specimen  is  said  to 
remain  indefinitely  unaltered.  The  solution  and  method  of  using  are  as  follows : 
formaldehyde  (forty  per  cent. ),  seven  hundred  and  fifty  cubic  centimetres  ;  distilled 
water,  one  thousand  cubic  centimetres  ;  potassium  nitrate,  ten  grammes  ;  potassium 
acetate,  thirty  grammes.  The  heart,  kidney,  and  brain  are  kept  during  a  period  of 
twenty-four  hours  in  Kaiserling's  fluid,  although  no  harm  is  done  if  they  remain 
thirty-six  to  forty-eight  hours.  The  specimen  is  then  transferred  to  alcohol  of  eighty 
per  cent.,  where  it  should  remain  for  not  longer  than  twelve  hours.  Subsequently 
it  is  to  be  put  in  alcohol  of  ninety-five  per  cent,  for  two  hours,  and  finally  preserved 
in  a  mixture  of  equal  parts  of  water  and  glycerin,  to  which  thirty  parts  of  potassium 
acetate  have  been  added. 

According  to  Orth,11  the  addition  of  ten  parts  of  a  forty  per  cent,  formaldehyde 
solution  to  one  hundred  parts  of  Muller's  solution  greatly  increases  the  preserving 


86o 


EXTRANEOUS    REMEDIES. 


and  hardening  action  of  that  solution.     As,  however,  the  compound  solution  begins 
to  decompose  in  two  days  after  its  mixing,  it  must  be  freshly  made  at  the  using. 

The  use  of  formaldehyde  for  the  preservation  of  milk  and  other  articles 
of  food  does  not  seem  to  us  justifiable;  although  when  employed  in  the 
proportion  of  i  :  5000  to  i  :  10,000  it  does  not  affect  the  taste.  It  has 
been  shown  by  A.  G.  R.  Foulerton*6  to  make  milk  more  indigestible, 
and  also  by  F.  W.  Tunnicliffe  and  O.  Rosenheim7  to  distinctly  affect 
assimilation  in  weak  children,  and  probably  to  increase  the  destruction  of 
nitrogen.  In  all  cases  observed  by  these  investigators  the  amount  of 
lecithin  in  the  faeces  was  diminished  by  the  formaldehyde. 

Formaldehyde  has  been  used  to  some  extent  in  human  medicine  as  a 
local  germicide  in  various  infective  diseases,  and  as  a  caustic  in  inopera- 
ble cancer"  also  by  inhalation  in  pulmonary  tuberculosis  and  chronic  bron- 
chitis.™ In  phthisis,  J.  Chowry-Muthu  employed  the  following  formula  : 
formalin  (40  per  cent. )  one  part,  chloroform  one  part,  rectified  spirits 
twenty-two  parts  ;  five  to  ten  drops  of  the  mixture  should  be  sprinkled 
on  cotton,  in  an  inhaler,  f  and  renewed  every  two  hours,  the  inhalations 
being  practised  for  five  to  eight  hours  a  day  as  continuously  as  possible. 

Formalin  has  been  used  as  an  intravascular  germicide,  but  its  value 
has  not  yet  been  determined.  It  does  not  seem  probable,  a  priori,  that 
the  treatment  should  be  beneficial  because  a  quantity  sufficient  to  exercise 
any  distinct  antiseptic  action  cannot  be  injected  without  jeopardizing  life. 
In  the  investigations  of  Fortescue-Brickdale,16  intravascular  injections  of 
formaldehyde  were  of  no  service  in  rabbits  infected  with  pneumococcus  or 
with  the  anthrax  germ  ;  and  similar  results  were  reached  by  W.  H. 
Park"  with  rabbits  infected  with  pneumococci  and  streptococci.  C.  C. 
Barrows,18  however,  in  one  case  of  violent  human  septic&mia,  believed 
that  life  was  saved  by  the  intravenous  injection  of  formaldehyde  ;  and  a 
similar  case  is  reported  by  W.  F.  Honan.19  In  these  cases  500-700  c.c. 
of  a  solution  of  formalin  (i :  5000  sterile  physiological  salt  solution)  were 
thrown  slowly  into  the  veins. 

VOLATILE  OILS. — The  general  properties  of  volatile  oils  have  been 
already  mentioned  in  the  Chapter  on  Aromatics  (see  page  623).  Cadeac 
and  Meunier  \  give  the  following  table  as  representing  the  time  which  it 
requires  the  pure  volatile  oils  to  destroy  the  typhoid  bacillus  : 


At  the  end  of 
Cinnamon  of  Ceylon  ....  12  minutes 

Cloves 25  minutes 

Eugenol 30  minutes 

Thyme 35  minutes 

Geranium  of  France   ....  50  minutes 


At  the  end  of 

Zedoary 2  hours 

Absinthe 4  hours 

Sandal  wood  .  .12  hours 


*  See  also  Bliss  and  Novy,  J.  Ex.  M.,  iv. 

t  A  pyramidal  inhaler  should  be  made  of  perforated  zinc,  flexible,  with  edges  bound 
with  velvet,  and  furnished  in  the  inside  with  leaden  clips  to  hold  the  cotton. 
J  Quoted  by  Sternberg  (Text  Book  of  Bacteriology,  N.  Y.,  1896,  p.  199). 


DISINFECTANTS.  861 

BENZOINUM— BENZOIN.     U.S. 

The  concrete  juice  of  Styrax  Benzoin,  a  large  tree,  native  of  Siam. 
The  drug  is  said  to  be  obtained  by  incising  the  tree  and  allowing  the 
juice  to  harden  as  it  exudes.  The  finest  specimens  of  benzoin  consist  of 
tears  agglutinated  together  ;  the  poorest,  of  brown  or  blackish  masses 
without  tears.  The  fracture  is  resinous,  the  surface  of  the  tears  smooth 
and  whitish,  the  odor  fragrant,  the  taste  at  first  very  slight,  afterwards 
somewhat  acrid.  The  chief  constituents  of  benzoin  are  resin  and  benzoic 
acid  ;  cinnamic  acid  is  also  frequently  present. 

Benzoic  Acid  (AciDUM  BENZOICUM,  U.  S. )  is  obtained  by  sublima- 
tion of  gum  benzoin.  As  thus  prepared,  it  is  in  white  feathery  crystals, 
of  a  silky  lustre,  a  warm,  peculiar  taste,  and  a  fragrant  vanilla-like  odor, 
due  to  the  presence  of  a  volatile  oil,  the  pure  acid  being  inodorous. 

Benzoic  acid  is  widely  distributed  through  the  vegetable  kingdom,  constituting 
the  peculiar  principle  of  all  true  balsams,  and  is  occasionally  present  in  the  urine 
of  grass-eating  animals.  It  is  a  normal  constituent  of  castor,  and  has  been  de- 
tected by  Seligsohn  *  in  the  suprarenal  capsules  of  an  ox.  It  is  used  considerably 
in  the  arts,  and  for  this  purpose  is  prepared  from  the  allied  hippuric  acid  of  horse 
urine,  and  also,  it  is  said,  from  naphtalin  :  these  forms  of  the  acid  should  never 
be  used  medicinally. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Benzoic  acid,  unless  in 
large  quantities  and  pure,  is  scarcely  irritant  to  mucous  membranes,  on 
which,  however,  it  exerts  a  distinct  alterative  influence.  As  a  germicide 
it  is  quite  active,  but  less  powerful  than  salicylic  acid. 

Absorption  and  Elimination. — Benzoic  acid  is  absorbed  rapidly,  and, 
as  was  first  discovered  in  dogs  by  Wohler,  and  afterwards  in  man  by 
Ure,1  it  is  eliminated  chiefly  from  the  kidneys,  united  with  nitrogenous 
atoms,  as  hippuric  acid.* 

It  has  not  yet  been  determined  where  in  the  body  the  hippuric  acid  is  formed, 
nor  yet  has  the  source  of  the  nitrogen  been  made  out.  Lewandowsky I5  in  five  exper- 
iments found  that  although  an  enormous  amount  of  hippuric  acid  was  excreted 
there  was  no  lessening  in  the  elimination  of  uric  acid,  and  hence  concludes  that 
there  is  no  relation  between  the  formation  of  the  two  acids.  It  has  been  suggested 
by  Kuhne  and  Hallwachs  that  the  conversion  occurs  in  the  liver  ;  but  the  researches 
of  Meissner  and  Shepard  *  appear  to  show  that  it  really  takes  place  in  the  kidneys. 

The  conversion  does  not  happen  in  the  intestines  or  in  the  blood,  since  after 
the  exhibition  of  large  doses  of  benzoic  acid  it  alone  can  be  detected  in  the  blood  ; 
and  after  the  administration  to  rabbits  of  large  amounts  of  hippuric  acid  by  the 
mouth,  only  traces  of  the  latter,  with  large  quantities  of  benzoic  acid,  can  be  found 
in  the  blood,  although  the  hippuric  acid  appears  in  the  urine  ;  t  further,  moderate 

*  Gusseron  found  hippuric  acid  in  the  urine  of  a  new-born  child  when  benzoic  acid 
had  been  given  to  the  mother  just  before  the  birth  ( Hoffmann  und  Schzvalbe's  Jahresb., 
1879,  283).  The  experiments  of  Von  Schrader  and  of  Mosso  (Arch.  Exper.  Path.  u. 
Pharm.,  1889,  xxvi.)  seem  to  show  that  the  whole  of  the  ingested  benzoic  acid  escapes 
with  the  urine. 

t  For  a  general  summary  and  latest  information,  see  paper  by  Van  de  Velde  and 
Stokvis  (Arch.  f.  Exper.  Path.  u.  Pharm.,  xvii.  189).  V.  Poulet  (Bull.  Soc.  de  Med. 
Prat.,  1888)  uses  the  hippurate  of  lime  and  lithia,  affirming  that  they  are  much  superior 
to  the  benzoates  in  ammoniacal  cystitis. 


862  EXTRANEOUS    REMEDIES. 

amounts  of  hippuric  acid  injected  into  the  blood  cause  severe  symptoms  of  poison- 
ing, which  is  not  true  of  benzoic  acid.  When  benzoic  acid  is  injected  freely  into 
the  blood,  a  portion  escapes  through  the  kidneys  unchanged.*  G.  Bunge  and  O. 
Schmiedeberg  have  also  found  that  in  the  dog  with  renal  arteries  tied  no  conversion 
of  benzoic  into  hippuric  acid  occurs,  but  that  tying  of  the  ureters  does  not  interfere 
with  the  change  and  have  succeeded  in  converting  benzoic  into  hippuric  acid  by 
passing  blood  containing  benzoic  acid,  with  or  without  glycocoll,  slowly  through 
the  kidneys,  removed  from  the  body  directly  after  death.  From  some  of  their  ex- 
periments it  would  seem  that  the  blood-corpuscles  play  an  important  role  in  the 
process,  as  when  serum  freed  from  blood-corpuscles  was  used,  at  most  only  a  trace 
of  hippuric  acid  was  formed.  According  to  Meissner  and  Shepard,  sometimes  the 
benzoic  is  converted  into  succinic  instead  of  hippuric  acid  in  man,  and  in  chickens 
it  is  habitually  changed  into  new  products,  one  of  which  is  nitrogenous. 

General  Effects. — The  influence  of  benzoic  acid  upon  the  general  sys- 
tem is  very  slight.  The  largest  therapeutic  doses  never  produce  any 
symptoms,  unless  it  be  those  of  slight  gastric  irritation  ;  a  half-ounce  of 
the  acid  taken  by  Schreiber  in  two  days  caused  only  an  increased  rapidity 
of  the  pulse-beat  and  moderate  disturbances  of  digestion. 

W.  Grube*  states  that  in  massive  doses  (i  to  5766  of  the  animal's  weight)  it 
produces  intoxication,  with  disturbance  of  circulation  and  respiration,  and  paralysis 
of  the  hind  feet,  and  that  the  antipyretic  influence  of  benzoic  acid  is  greater  than 
that  of  salicylic  acid. 

Nutrition. — Some  authorities  have  believed  that  benzoic  acid  distinctly 
affects  nutrition,  but  the  testimony  as  to  the  action  of  the  acid  upon  the 
elimination  of  urea  and  uric  acid  is  so  contradictory  as  to  indicate  that 
it  has  no  constant  powerful  influence  upon  protoplasmic  activities  or  upon 
nitrogenous  elimination. 

Ure,  Leroy  d'Etiolles,  and  Debouy  (quoted  by  Stille")  affirm  that  the  uric  acid 
is  very  much  diminished  or  altogether  absent,  while  Garrod  5  and  Keller  '  assert  that 
its  quantity  remains  normal.  Again,  Garrod  affirms  that  the  urea  is  very  much 
diminished  in  quantity,  Keller  and  Meissner  and  Shepard  declare  that  it  is  not  af- 
fected, and  in  the  elaborate  experiments  of  Carl  Virchow,7  sodium  benzoate  caused 
a  decided  increase  of  the  nitrogenous  elimination  from  the  kidneys. 

It  is  commonly  asserted  by  clinicians  that  the  acidity  of  the  urine  is 
increased  by  the  administration  of  benzoic  acid,  and  it  is  probable  that 
the  disappearance  of  uric  acid  crystals  from  the  urine  under  the  influence 
of  the  drug  is  due  to  the  conversion  of  insoluble  uric  into  soluble  hip- 
puric acid.  W.  W.  Ashhurst 8  asserts  as  the  results  of  experiments  made 
with  sodium  benzoate,  that  this  salt  does  not  increase  the  acidity  of  the 
urine,  and  that  the  mistake  of  clinicians  has  arisen  from  the  fact  that 
in  cystitis  the  urine  has  its  acidity  increased  by  the  drug  because  the 
ammoniacal  fermentation  is  checked  by  the  benzoic  acid. 

*  According  to  the  experiments  of  Th.  Weyl  and  B.  von  Anrep,  if  benzoic  acid  be 
given  to  man  or  animals  in  a  febrile  state  a  much  larger  proportion  of  it  than  usual  is 
eliminated  unchanged  (Hoffmann  und  Schwalbe's  Jahresb.,  1881,  447). 


DISINFECTANTS.  863 

Antiseptic  Influence. — In  April,  1872,  Dougall 9  announced  that  ben- 
zoic  acid  is  an  active  antiseptic.  Since  that  time,  numerous  experiments 
have  been  made  by  E.  Salkowski,10  Grube,  Bucholz,11  and  Fleck,12  with 
the  unanimous  result  of  ascribing  to  benzoic  acid  a  first  rank  in  destroy- 
ing bacteria  and  preventing  putrefaction.  In  most  of  these  investigations 
benzoic  acid  was  shown  to  be  much  more  active  than  salicylic  acid. 
Bucholtz  found  that  0.02  per  cent,  of  benzoic  acid  has  a  very  perceptible 
effect  upon  the  development  of  bacteria,  and  o.  i  per  cent,  inhibits  their 
growth  entirely  ;  also  that  the  sodium  benzoate  is  no  less  powerful  than 
the  pure  acid.  Kumagawa  determined  that  benzoic  acid  acts  powerfully 
as  an  intestinal  antiseptic,  notably  reducing  both  the  indican  in  the  urine 
and  the  number  of  the  bacteria  in  the  intestines. 

THERAPEUTICS. — Benzoic  acid  is  a  valuable  remedy  in  subacute  nasal 
and  respiratory  catarrhs,  also  in  chronic  bronchitis.  As  an  antizymotic  it 
is  considerably  used  by  the  Germans  in  diphtheria,  erysipelas,  and  allied 
diseases.  Senator,13  of  Berlin,  alleges  that  in  daily  doses  of  about  three 
drachms  it  is  equal  in  its  action  in  acute  rheumatism  to  salicylic  acid. 
Ure  first  suggested  the  employment  of  benzoic  acid  in  uric  acid  gravel 
and  calculus,  because,  as  he  thought,  it  diminished  the  excretion  of  uric 
acid  ;  and  Golding  Bird  subsequently  asserted  that  his  clinical  experience 
had  shown  the  value  of  benzoic  acid  in  uric  acid  diathesis.  It  certainly 
is  often  effective  in  causing  uric  acid  crystals  to  disappear  from  the  urine. 
In  the  phosphatic  urine  of  vesical  catarrh  benzoic  acid  often  acts  most 
happily  :  it  checks  fermentation  in  the  urine,  aids  in  the  solution  of  the 
phosphates,  and  acts  upon  the  mucous  membrane  of  the  bladder  as  an 
alterative  antiseptic.  In  ammoniacal  cystitis  the  drug  is  of  great  value. 
It  is  also  said  often  to  act  very  happily  in  acute  gonorrhoea. u 

Benzoic  acid  has  the  property  of  preventing  animal  fats  from  becoming 
rancid,  and  is  therefore  much  used  as  an  addition  to  ointments.  More- 
over, it  exerts  a  peculiar,  often  very  beneficial,  stimulant  action  upon  the 
skin,  and  is  very  useful  in  such  conditions  as  chapped  hands,  lips,  or 
nipples,  and  even  in  fissure  of  the  anus. 

There  would  seem  to  be  no  doubt  that  benzoic  acid  may  be  substi- 
tuted for  carbolic  or  salicylic  acid  in  antiseptic  surgery.  Under  the  name 
of  balsamiim  traumaticum,  a  preparation  practically  the  same  as  the  com- 
pound tincture  of  balsam,  was  formerly  much  used  as  a  vulnerary.  The 
practice  has  gone  out  of  vogue,  but  the  discoveries  concerning  antisepsis 
show  that  it  was  well  founded. 

ADMINISTRATION. — Gum  benzoin  is  never  used  itself,  but  is  exhibited 
in  the  form  of  the  tincture  (TiNCTURA  BENZOINI,  U.  S. ) — twenty  per 
cent., — dose,  one-half  to  one  fluidrachm  (2-4  C.c. );  and  of  the  com- 
pound tincture  (TINCTURA  BENZOINI  COMPOSITA,  U.  S. ) — twelve  per 
cent.,  used  in  chronic  bronchial  catarrh, — dose,  one  to  two  fluidrachms 
(4-8  C.c. ).  ADEPS  BENZOINATUS,  two  per  cent.,  U.  S. ,  contains  only 
enough  of  the  benzoin  to  preserve  the  lard,  and  is  employed  as  the  basis 
of  ointments.  Dose  of  benzoic  acid,  ten  to  thirty  grains  (o.  6-2  Gm. ) 


864  EXTRANEOUS    REMEDIES. 

in  capsules  ;  of  sodium  benzoate  (Soon  BENZOAS,  U.  S. ),  twenty  to  fifty 
grains  (1.3—3  Gm. ).  Ammonium  benzoate  (AMMONii  BENZOAS,  U.  S. ) 
occurs  in  white,  four-sided,  laminar,  nearly  odorless  crystals,  of  a  bitter, 
slightly  acrid  taste  ;  freely  soluble  in  water.  Dose,  ten  to  thirty  grains 
(0.65-1.95  Gm. )  dissolved  in  water. 

ACIDUM  CINNAMICUM. — Cinnctmic  acid  is  present  in  Peru  and  Tolu  Balsam, 
but  for  commercial  purposes  is  prepared  synthetically.  It  is  insoluble  in  cold 
water,  but  freely  soluble  in  boiling  water  and  alcohol.  It  has  been  used  in 
medicine  solely  in  the  treatment  of  tuberculosis,  especially  in  the  form  of  Sodium 
Cinnainate  (Hetol). 

As  originally  suggested  by  A.  Landerer,1  the  salt  is  to  be  given  intravenously, 
and,  according  to  Tobias,  the  same  vein  may  be  injected  from  fifty  to  sixty  times  in 
succession.  Most  extraordinary  results  have  been  claimed  for  the  method,  Lan- 
derer affirming  that  in  the  early  stages  of  uncomplicated  tuberculosis  eighty-five 
per  cent,  of  the  cases  can  be  cured.  The  heated  controversy  which  Landerer' s 
paper  gave  rise  to  has  been  well  reviewed  by  W.  J.  Robinson.*  It  does  not  appear 
probable  that  the  Landerer  treatment  will  accomplish  what  is  claimed  for  it,  and 
the  conclusion  of  Robinson,  that  sodium. cinnamate  is  not  a  direct  curative  agent  in 
tuberculosis,  and  is  of  no  more  value,  symptomatically,  than  is  creosote,  is  probably 
correct.  The  sodium  cinnamate  may  be  given  by  the  mouth  in  doses  of  from  two 
to  three  grains.  The  initial  dose  of  the  intravenous  treatment  should  not  exceed 
one-fiftieth  of  a  grain  ;  the  injection  may  be  made  every  third  day,  and  the  amount 
increased  until  one-third  of  a  grain  has  been  reached.  A  ten  per  cent,  solution  in 
glycerin  affords  an  excellent  method  of  administration. 


VI.— ACIDS   AND   ALKALIES. 

ACIDUM  SULPHUROSUM— SULPHUROUS  ACID.     U.  S. 

Sulphurous  Acid  of  the  U.  S.  Pharmacopreia  is  a  six  per  cent,  (by 
weight)  solution  of  sulphurous  acid  gas  (Sulphur  Dioxide)  in  water.  It 
is  a  colorless  liquid,  with  an  acrid  sulphurous  taste,  and  the  characteristic 
odor  of  burning  sulphur.  A  somewhat  elaborate  study  of  the  action  of 
the  sulphites  upon  vertebrata  has  been  made  by  Pfeiffer,1  who  finds  that 
they  are  poisonous  when  in  very  large  doses,  but  that  the  rapidity  with 
which  they  are  oxidized  into  the  sulphate  frequently  brings  about  sudden 
recovery  in  the  deepest  condition  of  poisoning.  In  sufficient  amount 
they  are  said  to  paralyze  the  blood-vessels,  the  heart,  and  the  respiratory 
apparatus. 

Sulphurous  acid  and  its  salts  are  most  efficient  in  destroying  the  low 
forms  of  life  which  are  connected  with  putrefaction  and  fermentation, 
and  for  this  reason  are  preservatives  of  organic  matters  ;  they  are  also 
among  the  oldest  of  disinfectants,  having  been  used  as  long  ago  as  1771; 
but  recent  experimental  evidence  indicates  that  they  have  not  the  great 
superiority  which  has  been  attributed  to  them. 

According  to  the  experiments  of  Sternberg,  i  volume  of  sulphurous  acid  gas 
in  100  volumes  of  air  is  sufficient  to  disinfect  dry  vaccine  matter.  As  these  experi- 
ments are  in  accord  with  older  observations,  they  may  be  considered  as  correct. 


DISINFECTANTS.  865 

According  to  Wernitz,  the  action  of  pepsin,  of  ptyalin,  of  invertin,  and  of 
diastase  is  prevented  by  the  presence  of  an  aqueous  solution  of  SO2  of  i  :  1317  to 
i :  8600  (by  weight);  while  the  action  of  myrosin  and  of  emulsin  is  neutralized 
by  i  :  21,000.  Wernitz  further  says  that  strips  of  woollen  or  cotton  goods  saturated 
with  putrefactive  matter  are  disinfected  by  exposure  of  from  four  to  six  hours  to  an 
atmosphere  containing  four  per  cent,  of  sulphurous  acid  gas.  The  very  elaborate 
experiments  of  Koch,  of  Wolffhiigel,  and  of  Sternberg  have  shown,  however, 
that  when  the  infectious  material  contains  spores  sulphur  dioxide  is  of  very  little 
efficiency. 

Sulphurous  acid  may  be  produced  very  cheaply  upon  a  large  scale 
by  the  burning  of  sulphur,  and  its  vapor  when  thrown  with  steam  into 
the  hold  of  a  vessel  mixes  with  the  water  of  the  vessel  and  with  the 
condensing  steam,  penetrating  into  all  the  cracks  and  places  where 
the  disease-germs  may  have  found  resting-place.  It  does  not  readily 
undergo  decomposition;  its  ordinary  salts  are  germicidal,  and  it  is  still 
relied  upon  for  the  disinfection  of  infected  ships.  On  the  other  hand,  in 
an  ordinary  room  it  does  not  find  water  in  which  to  dissolve;  it  is  liable 
seriously  to  impair  clothing,  bedclothing,  and  other  organic  material  of 
value;  and  as  formerly  made,  by  burning  in  a  simple  iron  pot,  it  was 
ineffective;  so  that  the  purification  of  apartments  by  burning  sulphur  in 
the  house  has  been  entirely  displaced  by  the  use  of  formaldehyde. 

The  sulphites  and  bisulphites  have  been  largely  employed  to  arrest 
or  control  fermentation,  and  are  useful  in  saturated  solution  in  various 
parasitic  diseases  of  the  skin. 

FLUORIDES. — Hydrofluoric  acid  gas,  dissolved  in  water, — i.e.,  commercial 
hydrofluoric  acid, — is  a  powerful  corrosive  which  hardens  the  skin  or  tissue  with 
which  it  comes  in  contact  and  continues  to  penetrate,  producing  great  pain.  It 
is  not  itself  used  at  all  in  medicine,  and  is  probably  unfit  for  any  therapeutic 
purposes. 

According  to  Tappeiner1  and  to  Waddell,  the  alkaline  fluorides  are  not  ex- 
tremely irritant,  and  when  taken  in  doses  of  from  one  to  one  and  a  half  grains  are 
depressants  to  the  circulation,  especially  affecting  the  vaso-motor  centres.  They 
have  been  used  to  some  extent  in  various  diseases,  but  have  given  no  promise  of 
usefulness  unless  it  be  in  the  treatment  of  goitre. 

As  germicides  the  fluorides  have  been  used  in  various  forms.  Under  the  name 
of  Fluorol,  the  Sodium  Fluoride  has  been  employed  in  a  two  per  cent,  solution  for 
the  treatment  of  infected  wounds.  The  Silver  Fluoride,  Tachiol,  is  a  feeble  coag- 
ulant of  albumin,  but  is  affirmed  by  Durante  and  Perez  to  be  in  i  :  1000  an  effective, 
very  penetrating,  not  pronouncedly  irritant,  germicide  which  may  be  used  in  various 
local  affections. 

Recently,  various  organic  fluorides  have  been  put  upon  the  market.  Accord- 
ing to  Tischer  and  Beddies,*  they  are  antispasmodics  and  bactericides. 

Di-fluor-diphenyl,  a  white  aromatic  powder,  insoluble  in  water,  freely  soluble 
in  alcohol,  has  been  recommended  as  a  ten  per  cent,  dusting-powder  or  a  ten  per 
cent,  ointment,  by  J.  Thimm  in  the  treatment  of  syphilitic  ulcerations.  Its  five  per 
cent,  ointment  has  been  exploited  as  Antitussin,  as  useful  when  applied  locally  in 
whooping-cough. 

Neodermin  is  a  five  per  cent,  ointment  of  fluor-pseudocumol,  said  to  act  like 
Antitussin. 

55 


866  EXTRANEOUS    REMEDIES. 

Fluoroform,  affirmed  by  Binz  *  to  have  properties  somewhat  similar  to  chloro- 
form, has  been  put  upon  the  market  under  the  name  of  Fluoroformol,  in  the  form 
of  a  two  and  eight-tenths  per  cent,  watery  solution,  which  is  almost  odorless  and 
tasteless,  and  is  said  to  be  non-toxic  and  non-irritant.  It  has  been  used  in  internal 
tuberculosis  in  doses  of  one  drachm  four  or  five  times  a  day,  but,  according  to  Gorl,4 
is  of  very  little  value. 

ACIDUM    BORICUM— BORIC   ACID.     U.  S. 

Boric  (or  Boracic)  acid  crystallizes  in  white  translucent  scales,  soluble 
in  about  thirty  parts  of  cold  water,  much  more  soluble  in  boiling  water, 
which  on  cooling  precipitates  all  but  about  twenty-three  grains  to  the 
fluidounce.  Hot  glycerin  dissolves  and  holds  upon  cooling  as  much  as 
three  drachms  to  the  fluidounce.  Borax  (SoDii  BORAS,  U.  S. )  occurs 
in  white,  flattened,  prismatic  crystals,  soluble  in  twelve  times  their  weight 
of  cold  water.  A.  Dujardin J  states  that  borax  is  incompatible  with  the 
alkaloids. 

PHYSIOLOGICAL  ACTION. — Local  Action. — Locally,  boric  acid  is, 
when  in  concentrated  form,  distinctly  irritant ;  in  dilute  solution,  stimu- 
lant and  antiseptic,  and  having  even  a  soothing  influence  upon  mucous 
membranes.  Its  sodium  salt  even  in  concentrated  form  is  scarcely  irri- 
tant. The  germicidal  power  of  boric  acid  and  its  salts  is  too  feeble  to  be 
relied  upon  in  cases  of  serious  infection. 

In  1874  Dumas  and  Schnatzles2  announced  that  borax  is  poisonous  to  the 
lower  forms  of  life.  In  Bucholz's8  experiments,  0.75  per  cent,  of  boric  acid  was 
found  sufficient  to  prevent  the  development  of  bacteria.  In  the  experiments  of 
Walb,*  a  two  per  cent,  solution  of  borax  distinctly  checked  the  putrefaction  of  so- 
lution of  fibrin  ;  a  five  per  cent,  solution  kept  the  solution  fresh  for  nineteen  days. 
Fresh  muscle-fibres  from  oxen  were  kept  fresh  many  days  by  a  one  per  cent,  solu 
tion.  Sternberg 5  found  that  boric  acid  and  sodium  biborate  are  inefficient  as  germ- 
destroyers,  but  have  considerable  antiseptic  power.  The  experiments  of  Sternberg 
have  received  corroboration  from  E.  Andrews.6 

Absorption  and  Elimination. — Boric  acid  and  its  soluble  salts  are 
freely  absorbed  and  eliminated,  escaping  to  some  extent  with  the  perspi- 
ration, saliva,  and  faeces,  but  chiefly  through  the  kidneys.  In  the  elab- 
orate experiments  of  Chittenden  and  Gies,7  twenty-four  to  thirty-six 
hours  were  found  to  be  generally  sufficient  for  the  complete  removal  of 
the  drug,  which  showed  no  tendency  to  accumulate  in  the  body.  W. 
Straub,8  on  the  other  hand,  affirms  that  twelve  hours  are  required  for  the 
elimination  of  half,  two  to  three  days  for  the  complete  throwing  off  the 
whole  of  the  single  large  dose. 

General  Effects. — The  general  physiological  action  of  boric  acid  and 
its  salts  is  very  feeble  ;  doses  of  one  hundred  and  fifty  grains  of  borax  a 
day  ordinarily  producing  no  distinct  symptoms.*  Poisoning  has,  how- 

*  G.  Lemoine  reports  (Bull.  Gen.  Therap.,  May,  1892)  a  bluish-gray  line,  like  that  of 
lead-poisoning,  as  present  upon  the  gums  in  cases  of  epilepsy  in  which  borax  had  been 
given  very  freely  and  continuously. 


DISINFECTANTS.  867 

ever,  resulted  from  the  too  free  use  of  the  drug  ;  the  symptoms  have 
varied  somewhat,  but  in  most  if  not  all  the  cases  there  have  been  great 
depression  of  spirits,  fall  of  bodily  temperature,  a  very  feeble  pulse, — 
rapid  or  slow, — and  an  erythematous  or  a  papulo- vesicular  eruption  ac- 
companied by  much  swelling  of  the  parts,  and  especially  affecting  the 
lower  extremities  and  followed  by  exfoliation  ;  nausea,  violent  vomiting, 
and  hiccough  have  been  present  in  some  cases  ;  ecchymoses  have  been 
noted  ;  the  mind  usually  remains  clear  until  late  in  the  poisoning,  but 
death  has  been  preceded  by  coma,  with  disturbances  of  the  respiration 
and  involuntary  discharges.* 

Serious  boric-acid  poisoning  is  very  rare,  and  we  have  no  knowledge  as  to  the 
amount  required  to  cause  death.  The  cases  whose  report  we  have  met  with  are: 
George  T.  Welch,9  two  ounces  of  boric  acid  in  the  vagina, — recovery ;  Modo- 
dewkow,10  death  from  washing  out  internal  cavities  with  five  per  cent,  solution; 
Hogner,11  death  from  washing  the  stomach  with  two  and  a  half  per  cent,  solution 
(see  also  Med.  News,  xl.  704).  There  is  no  reason  for  believing  that  boric  acid  had 
anything  to  do  with  the  symptoms  in  the  case  of  alleged  poisoning  reported  in  Med. 
News,  xliii.  199.  (See  also  71  G.,  Oct.  1901,  for  mild  cases.) 

In  the  experiments  made  by  H.  C.  Wood  and  E.  T.  Stewart,  enor- 
mous doses  of  boric  acid  salts  were  found  to  cause  in  the  frog  paralysis  of 
voluntary  motion  and  reflex  activity,  due  to  the  depression  of  motor 
spinal-centres,  the  nerves  and  muscles  not  being  affected.  The  saturated 
solution  of  sodium  cmadriborate,  brought  into  direct  contact  with  the 
heart,  was  feebly  depressant,  and  injected  in  enormous  amount  into  the 
jugular  vein  of  the  mammal  it  lowered  arterial  pressure. 

The  use  of  boric  acid  as  a  food  preservative  is  a  subject  of  great  impor- 
tance, involving  enormous  commercial  interests.  In  this  connection, 
however,  it  cannot  be  treated  in  full  detail,  but  we  give  the  following  out- 
line of  the  present  evidence: 

Boric  acid  is  undoubtedly  in  sufficient  dose  capable  of  killing  the  lower  animals, 
such  as  fish  and  frogs,  but  Liebreich  has  found  that  acetic  acid  is  at  least  twenty 
times  as  poisonous  to  the  fish  ;  and  Th.  Maass,15  that  common  salt  is  twice  as  toxic 
to  the  frog.  Given  in  sufficient  amount  to  mammals  it  is  apt  to  cause  gastro-intestinal 
irritation,  but  E.  de  Cyon  found  that  borax  added  to  meat  may  be  given  to  the  dog 
up  to  one  hundred  and  eighty  grains  a  day  without  disturbance  of  the  general  nutri- 
tion. The  question  involved  in  the  present  discussion  is,  however,  not  so  much 
the  effect  of  the  single  large  dose  of  boric  acid  as  the  influence  of  the  continuous 
use  of  the  drug  by  man  in  small  quantity.  In  the  experiments  of  Chittenden  and 
Giess  1.3  per  cent,  of  boric  acid  added  to  the  food  of  dogs  caused  no  albuminuria,  no 
disturbance  of  the  proteid  metabolism,  and  only  slight  vomiting — the  animals  gaining 
weight  rather  than  losing  under  continuance  of  the  diet ;  one  hundred  and  fifty  grains 

*  A  very  curious  effect  is  said  (Schiff,  Rev.  Med.  de  Suisse  Rom.,  1881,  244)  to  be  pro- 
duced by  the  local  application  of  boric  acid  to  nerves  :  the  part  affected  is  affirmed  to 
lose  its  power  of  originating  but  not  of  transmitting  impulses,  so  that  if  the  galvanic  cur- 
rent be  applied  to  the  part  of  the  nerve  which  has  been  exposed  to  the  drug  no  muscular 
contractions  result,  but  if  the  poles'be  placed  above  this  part  the  distal  muscles  respond 
at  once. 


868  EXTRANEOUS    REMEDIES. 

of  borax  per  day  failed  to  produce  in  the  dog  abnormal  urine.  Moreover,  Liebreich 
found  that  in  rabbits  killed  by  borax  the  kidney  structure  was  intact.  On  the  other 
hand,  Jacob  Plaut "  affirmed  that  boric  acid  will  produce  acute  parenchymatous  ne- 
phritis, and  Ch.  Fe're' 18  has  seen  albuminuria,  uraemia,  and  death  in  cases  of  human 
epilepsy  in  which  borax  had  been  given  continuously  for  a  length  of  time.  Harring- 
ton 19  maintains  that  the  failure  to  produce  toxic  effects  with  boron  derivatives  is  due 
to  too  short  periods  of  observation.  He  experimented  on  cats  to  which  were  admin- 
istered, over  a  period  of  one  hundred  and  thirty-three  days,  from  0.5-0.8  grammes 
of  borax.  At  the  end  of  this  period  every  animal,  except  one  which  had  received 
0.54  grammes  daily,  showed  pathological  changes  in  the  kidney.  In  the  studies  of 
Polli  eight  persons  took  for  forty-five  days  thirty  grains  daily  of  boric  acid,  and  then 
for  twenty-three  days  sixty  grains  daily  without  any  abnormal  symptoms  being  pro- 
duced. In  the  investigation  made  for  the  United  States  Department  of  Agriculture 
by  H.  W.  Wiley  twelve  young  men  were  placed  under  observation  for  repeated 
periods  of  thirty  to  seventy  days.  Each  period  was  divided  into  three  stages  :  the 
fore-period,  in  which  the  patient  was  kept  on  a  selected  diet  in  a  condition  of 
nitrogenous  equilibrium,  the  borax-period  in  which  the  same  diet  was  con- 
tinued with  the  administration  of  definite  quantities  of  borax  or  boric  acid,  and 
the  after-period  following  the  withdrawal  of  the  preservatives.  There  was  found 
a  diminution  in  the  quantity  of  nitrogen  eliminated  by  the  urine,  which  continued 
in  the  after-period,  and  a  distinct  augmentation  in  the  amount  of  phosphoric 
acid  in  the  urine,  with  loss  of  bodily  weight  brought  about  by  borax.  The  total 
solids  of  the  faeces  were  increased  and  the  total  solids  of  the  urine  diminished 
during  the  borax  periods,  and  this  relation  lasted  also  into  the  after-periods.  Taken 
in  conjunction  with  the  loss  of  bodily  weight,  which  was  an  almost  constant  symp- 
tom, these  results  show  that  the  borax  had  the  effect  of  lessening  the  assimilation 
of  food,  very  probably  through  the  disturbance  of  the  digestive  processes,  since 
when  more  than  four  or  five  grammes  (one  drachm)  of  borax  were  taken  daily  there 
were  distinct  symptoms  of  gastric  disturbance.  Wiley  Concludes  that  while  the 
normal  man  can  receive  quantities  of  boric  acid  or  borax,  amounting  to  one-half 
gramme  daily,  for  a  limited  period  of  time  without  loss  of  health,  the  long-continued 
use  of  the  salts  of  boric  acid  creates  disturbances  of  the  appetite  and  digestion. 
The  results  of  Wiley,  so  far  as  nitrogen  elimination  is  concerned,  are  in  disagree- 
ment with  those  of  Gruber,16  who  found  that  after  large  doses  (5-10  grammes  daily) 
there  is  an  increased  elimination  of  nitrogen,  phosphoric  acid,  and  sulphuric  acid. 
This  has  been  confirmed  by  Chittenden  and  Gies.  They  state  that  if  the  doses  of 
boric  acid  did  not  decidedly  exceed  fifty  grains  a  day,  no  influence  was  exerted 
upon  proteid  metabolism  or  the  general  bodily  nutrition,  or  the  kidneys. 

The  above  summary  of  the  present  knowledge  shows  that  the  evidence 
in  regard  to  the  propriety  of  using  boric  acid  as  a  food  preservative  is,  as 
in  most  questions  involving  enormous  pecuniary  interests,  more  or  less 
contradictory,  but  certainly  demonstrate  that  foods  preserved  by  boric 
acid  are  much  inferior  to  fresh  foods.  How  far,  if  at  all,  they  are  inferior 
to  foods  preserved  by  sodium  chloride,  and  especially  by  potassium 
nitrate,  is  uncertain.  It  seems  to  us  doubtful  whether  boric  acid  is  more 
deleterious  than  is  saltpetre.  The  fact  is  that  all  salt  foods  are  of  difficult 
digestion,  and  that  both  boric  acid  and  saltpetre  are  irritant  to  the  kidneys.* 

*  The  most  important  recent  publications  opposed  to  the  use  of  boric  acid  are  Borsaure 
als  Konservierungsmittel  (E.  Rost,  Berlin,  1903);  Wiley,  United  States  Department  of 
Agriculture,  Bureau  of  Chemistry,  Bulletin  No.  84.  In  favor  of  it :  Boron  Food  Preserva- 
tives, Perkins,  Bacon  &  Co.,  Fleet  Street,  London;  Borax  and  Boracic  Acid  (Oscar 
Liebreich,  Berlin,  1899) ;  Wirkung  der  Borsaure  und  des  Borax  (Oscar  Liebreich, 
1903,  Berlin). 


DISINFECTANTS.  869 

THERAPEUTICS. — As  originally  suggested  by  Rosenthal,"  boric  acid 
has  been  found  to  be  an  efficient  remedy  in  cystitis  with  ammoniacal  urine, 
rendering  the  urine  acid  probably  by  checking  the  fermentation.  In  our 
own  practice  great  relief  has  been  obtained  in  the  cystitis  of  spinal  dis- 
eases by  washing  out  the  bladder  with  a  few  ounces  of  a  saturated  solu- 
tion of  boric  acid  after  the  use  of  the  catheter.  The  acid  may  be  given 
in  doses  of  ten  grains  (o.  6  Gm. )  three  to  six  times  a  day  ;  the  salt, 
twenty  grains  to  a  drachm  (1.3-4  Gm. ):  in  each  case  administered  in 
diluted  watery  solution.  As  a  disinfectant  and  soothing  eye-wash  its 
solution  is  much  used  in  conjunctivitis — from  five  grains  to  the  ounce  up 
to  saturation.  Boric  acid  is  also  employed  as  an  antiseptic  dressing  to 
fresh  wounds,  abscesses,  old  burns,  etc.  (See  M.  Greene.13) 

Wounds  dressed  in  a  dry  manner  with  a  lint  soaked  in  a  saturated  solution  of 
boric  acid  and  dried,  are  stated  to  heal  as  rapidly  as  when  a  complicated  antisepsis 
is  employed.  Greene  prepares  an  ointment  by  melting  one  part  each  of  spermaceti 
and  white  wax  with  six  parts  of  vaseline,  and  adding,  while  hot,  two  to  four  parts  of 
a  saturated  glycerite  of  boric  acid. 

The  saturated  solution  of  boric  acid  has  been  especially  recommended 
in  phlegmonous  erysipelas.  Both  boric  acid  and  borax  are  of  excellent 
service  in  aphthous  ulceration,  diphtheria,  and  other  inflammations  of  the 
mouth,  in  which  crystals  of  the  salt  may  be  allowed  slowly  to  dissolve  in 
the  mouth.  C.  F.  Folsom  M  has  strongly  recommended  borax  in  the  dose 
of  fifteen  grains  three  times  a  day  in  epilepsy.  We  have  tried  the  remedy 
carefully  in  a  large  number  of  cases,  increasing  the  dose  until  pronounced 
gastro-intestinal  irritation  was  caused,  without  affecting  perceptibly  the 
return  or  the  severity  of  the  paroxysms. 

GLYCERITUM  BOROGLYCERINI.  U.  S. — Glycerite  of  Boroglycerine  is  a 
thirty-one  per  cent,  solution  of  boric  acid  in  glycerin  which  is  much 
used  as  a  local  application  either  in  full  strength  or  diluted. 


PRACTICAL   DISINFECTION. 

It  is  not  proposed  to  discuss  here  the  many  larger  questions  in  regard 
to  disinfection,  such  as  the  proper  care  of  sewerage,  which  belongs  to  the 
province  of  the  sanitary  engineer  rather  than  to  the  daily  routine  of  the 
medical  practitioner.  It  may  be  well,  however,  to  point  out  that  whilst 
foul  water-closets  in  cities  have  long  been  the  subject  of  much  attention 
and  discussion,  in  country  districts  privies  are  usually  left  to  their  own 
noisome  devices  ;  a  condition  of  total  depravity  which  can  be  readily 
prevented  by  simply  standing  in  the  outhouse  a  barrel  containing  one 
part  of  lime  mixed  with  three  or  four  parts  of  dry  earth  ;  a  small  shovel- 
ful to  be  thrown  into  the  receptacle  immediately  after  use  ;  and  by  the 
periodical  withdrawal  of  the  comparatively  inoffensive  mass  resulting. 


870  EXTRANEOUS    REMEDIES. 

The  problems  of  the  practical  physician,  so  far  as  disinfection  is  con- 
cerned, are  three  in  number,  as  follows  : 

First.  —  The  preparation  of  the  room  for  the  reception  of  the  person 
suffering  from  contagious  disease.  All  closets  should  be  emptied,  all 
articles  of  ornament  and  unnecessary  furniture  should  be  removed,  and 
such  as  is  allowed  to  remain  should  be  free  from  upholstery,  and  drawers 
or  other  receptacles  be  kept  as  empty  as  may  be.  Carpets  should  be 
reduced  to  a  single  small  rug  or  removed  altogether,  the  nurse  finding 
protection  for  her  feet  in  cold  weather  by  the  use  of  heavily  lined, 
soft,  high  slippers.  The  ceiling,  the  walls,  the  surbases,  the  floor,  the 
closets,  should  be  thoroughly  cleaned  with  abundance  of  soap,  washing- 
soda,  and  hot  water,  special  care  being  taken  with  all  crevices  or  joints. 

Second. — Disinfection  during  occiipancy  of  the  room  by  the  patient. 
It  is  now  generally  recognized  that  to  attempt  the  destruction  in  the 
air  of  the  widely  spread  germs,  such,  for  example,  as  exist  in  a  small- 
pox epidemic,  is  childish,  but  it  is  not  so  universally  recognized  that 
the  effort  to  destroy  organic  germs  in  the  air  of  the  room  during  occu- 
pancy is  equally  futile.  No  person  can  live  in  an  air  which  contains 
any  known  germicide  in  sufficient  amount  to  kill  disease  germs  ;  and  the 
putting  of  saucers  or  other  receptacles  of  chlorinated  lime  about  a  sick 
room  is  a  mediaeval  barbarity  which  should  never  be  permitted,  because  it 
tends  to  the  production  of  a  false  sense  of  security.  The  air  of  the  sick- 
room must  be  kept  pure  by  the  checking  of  the  discharge  into  it  of  the 
disease  germs,  but  especially  and  chiefly  by  free  ventilation,  not  from  one 
room  into  another,  but  directly  in  some  way  into  the  open  air,  so  that 
the  disease  germs  may  be  widely  distributed  and  the  patient  supplied 
with  an  abundance  of  proper  breathing  material.  The  source  of  the  pois- 
onous germs  is  the  body  of  the  patient,  and  it  is  a  matter  of  the  most  vital 
importance  to  destroy  these  germs  as  largely  as  possible  at  the  point  of 
discharge.  In  many  contagious  diseases  the  pathogenetic  organisms  are 
thrown  off  in  large  quantities  with  the  urinary  and  faecal  discharges; 
often  they  escape  through  the  skin  and  through  the  sputum  or  other 
infected  discharges  from  the  body.  All  such  excretions  should  be  pois- 
oned as  soon  as  they  leave  the  body;  the  disinfectant  should  be  placed 
in  the  receptacle  before,  not  after,  it  is  used.  Moreover,  the  discharges 
should  be  allowed  to  stand  mixed  with  the  concentrated  germicide  until  suf- 
ficient time  has  elapsed  for  it  to  kill  the  organisms.  Chamber-pots  and 
other  receptacles  should  therefore  not  be  immediately  emptied  after  use. 
To  allow  any  excretion,  sputum,  or  other  infected  discharge  to  exist  for 
a  moment  undisturbed  is  most  culpable  neglect.  Spit-cups,  urinals, 
etc. ,  should  have  the  disinfectant  in  them  whilst  waiting  for  use. 

As  the  skin  is  often  the  channel  of  elimination  of  the  disease  poison, 
frequent  washing  of  the  patient  is  essential,  and  care  must  be  taken  that 
the  water  which  has  been  used  should  not  be  emptied  before  it  has  been 
disinfected. 

Of  all  the  germicides,  by  reason  of  its  cheapness  and  efficiency,  chlori- 


DISINFECTANTS.  871 

nated  lime  is  usually  preferable  for  the  disinfection  of  germs  in  discharges. 
Carbolic  acid  or  formaldehyde  may  be  used.  Corrosive  sublimate,  on 
account  of  the  ease  of  its  decomposition  and  of  the  danger  of  having  its 
solution  about  the  sick  room,  is  scarcely  applicable  to  the  present  pur- 
pose. As  the  cost  of  chlorinated  lime  is  practically  nothing  it  should  be 
used  very  freely. 

The  clothing  of  the  patient  should  be  cotton,  and  with  the  sheets 
often  changed.  In  this  changing  it  suffices  to  place  a  clean  sheet  upon 
the  floor  and  throw  into  it  the  discarded  clothing  and  bedding,  then  tie 
the  whole  into  a  hard  ball  and  drop  it  into  boiling  water  without  open- 
ing, and  allow  it  to  remain  for  over  half  an  hour  until  all  organisms  have 
been  destroyed.  This  method  has,  however,  the  objection  of  fixing 
permanently  in  the  muslin  all  stains  from  blood,  faeces,  and  organic  dis- 
charges. It  is  better,  therefore,  and  in  a  hospital-ward  it  is  essential,  to 
throw  the  personal  and  bedclothing  piece  by  piece  when  taken  off  di- 
rectly into  a  covered  vessel  containing  a  disinfecting  solution.  Accord- 
ing to  the  experiments  of  A.  C.  Abbott,  corrosive  sublimate  is  actively 
mordant,  and  should  not  be  used.  Chlorinated  lime,  o.  5  per  cent,  solu- 
tion, in  cold  water,  is  effective,  does  not  fix  stains,  and  though  theoretically 
..  should  attack  the  structure  of  various  fabrics,  practically  has  no  per- 
ceptible influence  unless  after  repeated  immersion.  Probably  the  best 
disinfectant  solution  for  this  use  consists  of  carbolic  acid,  five  parts  ;  com- 
mon soft  soap,  three  parts  ;  cold  water,  one  hundred  parts.  After  two 
hours'  soaking  in  such  a  mixture  the  clothing  must  be  taken  out  and  well 
washed  in  water  at  a  temperature  not  exceeding  roo°  F.  until  all  stains 
have  been  removed. 

Absolute  cleanliness  in  regard  to  the  room  itself  must  be  strictly 
enforced  during  the  whole  period  of  sickness,  and  in  many  cases  it  is  ad- 
visable to  mop  the  floor,  surbases,  windows,  etc.,  with  water  containing 
ten  per  cent,  of  formaldehyde. 

Third.  — Disinfection  of  apartments  that  have  been  used.  The  process 
of  purifying  an  infected  room  naturally  divides  itself  into  two  parts, — first, 
the  killing  of  the  germs  ;  second,  the  cleaning  of  the  room  ;  and  these 
two  acts  should  always  follow  in  the  order  here  given  so  as  to  lessen  as 
much  as  possible  the  danger  to  the  operator  and  to  the  surrounding  habi- 
tations which  would  be  caused  by  the  dispersion  of  the  active  germs. 
When  the  room  has  been  thoroughly  prepared  and  properly  taken 
care  of  during  its  occupancy  its  purification  is  very  simple.  First,  all 
clothing  and  bedding  must  be  disinfected,  and  the  most  efficient  and  use- 
ful agent  in  so  doing  is  heat.  In  cities,  in  quarantine  stations,  and  other 
places  where  proper  apparatus  is  forthcoming,  all  articles  of  the  character 
spoken  of  should  be  exposed  to  the  prolonged  effect  of  hot  steam  in 
closed  chambers.  When  this  is  not  possible,  whatever  can  be  boiled 
without  injury  should  be  boiled  for  at  least  forty  minutes.  Such  articles  as 
cannot  be  boiled  may  be  immersed  in  a  i :  1000  solution  of  corrosive  sub- 
limate over  night,  or  preferably  in  a  two  per  cent,  carbolic  solution, 


872  EXTRANEOUS    REMEDIES. 

and  then  thoroughly  washed.  To  those  articles  of  clothing  or  bedding 
to  which  none  of  these  processes  are  available  without  serious  injury,  fire 
should  be  applied  if  the  infection  has  been  at  all  severe.  All  articles  of 
furniture  should  be  washed  with  a  solution  of  corrosive  sublimate, 
i :  500,  care  being  taken  to  see  that  the  solution  is  well  applied  to 
cracks,  joints,  etc.  Twenty-four  hours  later  the  furniture  may  be  sponged 
off  with  an  ordinary  solution  of  soap  and  water. 

In  the  further  purification  of  the  room,  it  must  be  remembered  that  it 
is  not  chiefly  the  air  which  is  to  be  purified  but  the  various  solid  surfaces 
and  bodies  on  which  germs  have  found  lodgement.  The  best  of  the 
germicides  for  this  purpose  is  undoubtedly  formaldehyde.  It  is  used  in 
practice  in  various  ways.  It  is  demonstrated  that  the  moist  gas  acts 
very  much  better  than  does  the  dry,  and  in  our  opinion  the  best  method 
of  applying  formaldehyde  is  by  means  of  a  spray  or  atomizing  apparatus, 
which  should  throw  a  finely  broken  spray  al  over  the  surbases,  walls, 
floors,  etc.,  so  as  to  bring  the  formaldehyde  in  direct  contact  with  the 
infected  surfaces  in  excessive  amount.  The  ordinary  spray  pump  used  by 
fruit-growers  suffices  for  an  impromptu  disinfection,  but  is  better  replaced 
by  a  special  atomizer  when  much  work  is  to  be  done.  The  rule  of  the 
Philadelphia  Health  Bureau  in  regard  to  the  strength  and  amount  of  the 
solution  to  be  used  seems  to  us  correct.  A  solution  of  equal  parts  of 
water  and  of  the  official  watery  solution  of  formaldehyde  is  sprayed  upon 
all  the  surfaces  of  the  room  in  the  proportion  of  three  pints  of  the  solution 
to  one  thousand  cubic  feet  of  air  space  in  the  room. 

In  lecture-rooms,  with  abundant  benches,  and  in  some  other  peculiar  apart- 
ments, it  is  possible  that  this  amount  of  solution  would  not  suffice  to  cover  all  sur- 
faces. Under  these  circumstances  sufficient  of  the  disinfecting  fluid  should  be  used 
to  wet  every  surface  in  the  room.  We  are  informed  by  Dr.  A.  C.  Abbott,  Chief  of 
the  Philadelphia  Health  Bureau,  that  they  secure  by  means  of  the  solution,  sprayed 
in  the  manner  above  related,  one  hundred  per  cent,  of  disinfection,  that  is  to  say, 
all  test  objects  placed  in  a  room  have  their  germs  destroyed  by  it.  It  is  essential 
that  the  work  be  done  quickly,  and  in  very  large  rooms  several  operators  should 
work  at  the  same  time  ;  since  the  liberation  and  diffusion  of  the  formaldehyde  gas 
will  very  soon  drive  the  operators  from  the  chamber. 

By  means  of  the  formaldehyde  lamp,  or  various  vaporizers,  it  is  pos- 
sible to  disinfect  the  apartment  without  the  direct  use  of  atomization.  If 
the  atomizer  be  used,  one  part  of  a  saturated  solution  of  formaldehyde 
may  be  added  to  four  parts  of  water,  so  as  to  make  a  twenty  per  cent, 
solution.  After  the  treated  room  has  been  shut  twenty-four  hours  it  may 
be  opened,  freely  ventilated,  and  thoroughly  cleaned  with  abundant  use 
of  fresh  water,  soap,  washing  soda,  scrubbing-brush,  and  physical 
exercise. 

When  it  is  necessary  to  disinfect  a  room  which  has  not  been  properly 
prepared  or  taken  care  of  during  a  past  illness,  the  method  of  procedure 
is  in  general  similar  to  that  just  described,  but  different  in  some  minor 
details.  All  small  articles  which  can  be  without  injury  purified  by  heat, 


DISINFECTANTS.  873 

either  in  the  steam-chest  or  by  boiling,  should  be  so  treated.  All  articles 
which  cannot  be  so  acted  upon  without  injury  should  be,  with  the  furni- 
ture, well  washed  with  the  corrosive  sublimate  solution ;  or  if  the  character 
of  the  articles  forbids  this,  may  be  disinfected  with  formaldehyde.  For 
this  purpose  the  articles  must  be  taken  out  of  the  drawers  and  placed  in 
position  where  they  will  be  fully  exposed  in  all  their  surfaces  during  the 
process.  Books  should  be  set  upright  on  tables,  and  opened  as  widely 
and  freely  as  possible,  so  the  leaves  hang  loose  and  separate.  Engravings 
and  paintings  may  be  freely  exposed  by  the  removal  of  the  glass-covering 
or  other  method  to  the  action  of  the  formaldehyde,  and  should  in  the  case 
of  paintings  be  sponged  carefully  with  lukewarm  water  immediately  after 
being  exposed  to  the  fumes  of  the  formaldehyde.  Corrosive  sublimate  is 
not  to  be  used  on  metallic  articles,  or  on  those  of  marble  or  other  lime  salt; 
these  substances  are  not,  however,  affected  by  formaldehyde.  The  clean- 
ing of  the  room  after  disinfection  should  be  extremely  thorough. 

Prisons,  hospital-wards,  houses  which  have  been  inhabited  by  tuber- 
culous patients,  and  other  edifices,  are  liable  to  become  so  infected  with 
organisms,  especially  with  tubercular  organisms,  that  the  processes  detailed 
are  not  sufficient.  Frequently  such  buildings  are  more  or  less  out  of 
repair;  when  this  is  the  case,  all  decomposed  wood  should  be  torn  out 
and  left  out  during  the  process  of  disinfection.  (See  below. )  Moreover, 
not  rarely  in  these  buildings  the  most  rigid  disinfection  will  fail  to  destroy 
germs  which  work  their  way  into  absorbent  walls  or  wood  surfaces  or 
deep  crevices,  so  that  scraping  off  of  the  plaster  and  tearing  out  of  the 
rooms  may  be  necessary  for  the  purification  of  the  apartment.  If  the  germs 
are  active,  as  are  those  of  typhus  fever,  in  order  to  protect  the  workmen, 
a  superficial  disinfection  should  precede  these  destructive  acts.  In  many 
of  these  cases  the  first  stage  of  disinfection  should  consist  of  a  free  appli- 
cation, by  means  of  mops,  of  a  four  per  cent,  boiling  solution  of  caustic 
soda  to  ceilings,  walls,  surbases,  floors,  sinks,  drains.  Such  a  hot  alka- 
line solution  acts  very  decidedly  upon  the  germs  themselves  and  rapidly 
destroys  all  kinds  of  filth,  and  thereby  exposes  the  germs  to  the  after- 
action  of  more  generally  recognized  germicides.  A  day  or  two  after  the 
use  of  the  soda  the  apartment  should  be  thoroughly  washed  out  with 
plain  warm  water.  When  there  are  wide  cracks  or  crevices,  corrosive 
sublimate  solution,  I  :  200,  should  be  freely  used  before  the  alkaline  solu- 
tion, which  will  decompose  and  render  innocuous  any  excess  of  the  mer- 
curic chloride.*  Whenever  there  is  a  metal  surface,  such  as  occurs  in 
sinks,  drains,  pipes,  etc. ,  the  two  to  five  per  cent,  carbolic  acid  solution  is 
preferable  to  the  corrosive  sublimate;  or  a  ten  per  cent,  solution  of  for- 
maldehyde may  be  used.  After  the  processes  spoken  of  have  been  car- 

*  In  this,  as  in  many  other  cases,  when  there  is  danger  of  corrosive  sublimate  being 
decomposed  by  organic  or  alkaline  substances,  the  solution  is  made  more  effective  by  the 
use  of  hydrochloric  acid.  Half  an  ounce  of  mercuric  chloride,  two  ounces  of  strong  hydro- 
chloric acid,  and  three  gallons  of  water,  make  a  very  effective  solution,  not  so  readily 
decomposed  as  the  simple  mercuric  chloride. 


874 


EXTRANEOUS    REMEDIES. 


ried  out,  the  final  disinfection  may  be  made  by  mopping  out  with  large 
quantities  of  the  formaldehyde  solution;  or  in  some  instances  chlorinated 
or  formaldehyde  lime-wash,  as  detailed  below,  is  preferable. 

Formaldehyde  vapor  is  often  used,  but  is  certainly  less  effective  than 
the  application  in  mass  of  the  formaldehyde  solution  to  the  various  room 
surfaces. 

Infected  stables  offer  problems  differei-t  from  those  of  ordinary  build- 
ings; the  tetanus  germ  exists  in  the  soil,  and  when  the  infection  of  the 
stable  is  with  this  bacillus,  the  removal  of  the  animals  to  another  locality 
and  the  torch  are  almost  the  only  resource.  The  products  of  animal 
and  vegetable  decomposition  are  so  abundant  about  stables  that  corrosive 
sublimate  is  of  very  little  use,  except  for  washing  off  mangers  and  similar 
objects.  Further,  in  the  case  of  dairy  stables,  carbolic  acid,  chlorine, 
and  other  disinfectants  which  have  strong  and  persistent  odors,  cannot 
well  be  employed  because  they  are  liable  to  damage  the  milk  for  a  long 
time  after  their  use.  The  first  step  in  the  disinfection  of  a  stable  is  the 
removal  and  destruction  of  all  rubbish,  loose  boards,  and  decomposed 
wood.  Then  the  absolute  cleaning-up  of  the  stable  with  a  solution  of 
sodium  carbonate.  Floor,  walls,  ceiling,  wood-work  of  the  stable  should 
finally  be  deluged  with  lime-wash  containing  chlorinated  lime,  or  formalde- 
hyde solution.  The  chlorinated  lime  is  cheap  and  equally  effective  with 
the  formaldehyde  when  there  is  no  special  objection  to  its  use.  From  six 
to  eight  ounces  of  the  chlorinated  lime  may  be  added  to  each  gallon  of 
lime-wash;  or  the  official  formaldehyde  solution  may  be  used  in  the  pro- 
portion of  i :  30  to  i :  20.  Hay,  straw,  manure,  and  the  general  refuse  of 
an  infected  stable  may  be  destroyed  by  fire,  or  may  be  preserved  for  use 
as  a  fertilizer  by  mixing  it  with  chlorinated  lime  and  allowing  it  to  stand 
for  some  weeks. 

In  all  cases  of  disinfection  success  depends  upon  the  thoroughness  with 
which  the  process  is  carried  out. 

The  following  table  has  been  compiled  by  H.  C.  Wood,  Jr. ,*  showing 
the  solutions  of  various  germicides  equivalent  to  a  i :  2000  or  a  i :  10,000 
corrosive  sublimate  solution  : 


Mercury  bichloride  .   . 
Mercury  biniodide  .   . 
Silver  nitrate     .... 

:  2000 
=  3000 

'  4.OO 

i:  10,000 
i:  15,000 
1:4000 
i:  looo 
1:150 
1:150 
i:  loo 

i:75 
i  •  500 

Creosote      

.    .    .  i:  too 

Sulphuric  acid    

.    .    .  i:  100 

Sulphurous  acid    .       ... 

I'  SO 

Chlorinated  lime  .    .    . 
Formaldehyde  .... 

:  100 

•  CQ 

Sodium  hydrate     

.    .    .  i:  100 

Licjuor  sodss  chlorinata 

I  '  SO 

Lysol  

:4o 
:3o 
:5 

Phenol  sodique      ..... 

i:  25 

Phenol    

Platt's  chlorides     

.    .   .  i  :  20 

Creolin    

Aq.  hydrogen  dioxid    .    .    . 
Alcohol            .   . 

.  .   .1:3 

.  i"  ^ 

Iodine     

Salicyle  acid  

1:150 

Listerine          

.  pure 

Cupri  sulphate  

.  oure 

Thymol  

1:150 
i:  loo 

Ichthyol    

.  .   .  pure 

Potassium  permanganate  .   .   . 

DISINFECTANTS. 


875 


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21.  HOPPE-SEYLER    .  A.  G.  P.,  1872,  v.  470. 

22.  CHRISTIANI    .  .   .  Z.  P.  C.,  ii. 

MUNK Arch.  f.  Thierheilk.,  viii. 

104. 
NEUMANN  ....  Arch.  f.  Derm.  u.  Syphil., 

1869,  i.  425. 
KEMPSTER  .   .   .   .  A.  J.  M.  S.,  July,  1868. 

TURTSCHANINOW  .  A.  E.  P.  P.,  1894,  XXXIV. 


De  1'Acide    Phfiniqne,  2d 

ed.,  Paris,  1865. 
S.  Jb.,  civ.  274. 


LEMAIRE 

HUSEMANN 

BERB  and  JOGEL  .  Gaz.  Med.,  1872. 

STONE  .   .    .   .   .   .  P.  M.  T.,  ix. 

GIES A.  E.  P.  P.,  xii.  401. 

HARE T.  G.,  1887,  519. 

ERLS S.  Jb.,  clxiv.  148. 

REUDER Journ.    de    Pharm.   et   de 

Chim.,  1871,  456. 
DESPLATS  .  .   .  .  G.  H.  M.  C.,  1880,  xvii. 

Ascon Bull.  d.   Accad.  di  Roma, 

1899,  495- 
HEDDAEUS     .  .  .  M.  M.  W.,  1898,  xlv.  367. 

WOOD,  JR Merck's  Archives,   1899,  i. 

191. 

EAMES     B.  M.  J.,  May,  1873. 

HUETER D.  Z.  Ch.,  1874,  iv. 

AUFRECHT  .   .   .   .  C.  M.  W.,  1874,  129. 
SENATOR     .   .   .   .  B.  K.  W.,  1876,  69. 

MADER Cb.  C.,  1877,  376. 

KUNZE C.  M.  W.,  1874,  479. 

HAGEN S.  Jb.,  clxiv.  146. 

SCHMIDT     ....  Cb.  C.,  1876,  552. 

TAYLOR A.  J.  M.  S.,  April,  1882. 

HARRIS L.  L.,  Nov.  1896. 

TAYLOR P.  M.  T.,  ii.  284. 

L.  L.,  1869,  i. 

NAPIER Trans.    Med. -Chir.  Soc., 

Edinburgh,  ii.  75. 

FALCKSON  .   .   .   .  A.  K.  C.,  xxvi.  204. 
WALLACE   .  .   .  .  B.  M.  J.,  April,  1870. 

S.  Jb.,  cci.  129. 
KOHLER S.  Jb.,clv.  276. 

L.  M.  R.,  Oct.  15,  1887. 
FRANKENBURGER  .  In.  Dis.,  Erlangen,  1891. 

S.  Jb.,  ccii.  238. 

S.  Jb.,  clxiv.  144. 

BAUMANN  and  HUETER  .  Z.  P.  C.,  i. 
BAUMANN  and  HUETER  .  M.  T.  G.,  ii. 

CERNA P.  M.  T.,  ix. 

CAFRAWY    ....  Thesis,  Paris,  1881. 

TAUBER A.  E.  P.  P.,  1895,  xxxvi. 

SZYDLOWSKY    .   .  St.   Petersb.   Med.  Woch., 

1883,  x.  87. 

MARFORI    .   .   .  .  A.  I.  B.,  1894,  xxii. 
COURMONT  and  Do  YON  .  N.  Cb.,  1899. 

BITTER B.  M.  J.,  1890. 

FLIESBURG     .  .   .  Northwestern  Lancet,  Dec. 

1891. 

GERLACH    ....  Zeitsch.  f.  Hygiene,  June, 
1891. 

S.  J.  Bd.,278. 
VAN  ERMENGEN  .  B.  A.  R.  B.,  1889,  60. 


876 


EXTRANEOUS    REMEDIES. 


REFERENCES. —  Continued. 

73.  BURGESS L.  L.,  June  23,  1900. 

74.  MUTSCHLER  .   .   .  Annals    of   Surgery,   1901, 

xxxiv.  558. 

75.  HARRINGTON    .   .  A.  J.  M.  S.,  1900,  cxx.  2. 

76.  ASCHER N.   Y.   M.  J.,   1904,  Ixxix. 

743- 

77.  CLARK  and  BROWN  .  J.  A.  M.  A.,  1906,  xlvi. 

"8-> 


2.  KUSSNER 

3.  BLUM    .  . 

4.  HENRY    . 

5.  SOLLY  .   . 

6.  BUCHOLZ 

7.  FISCHER  . 


.  M.  T.  G.,  1878,  716. 
.  D.  M.  W.,  1891,  xvii. 
.  M.  News,  Sept.  18,  1887. 
.  Centralb.  f.  d.  ges.Therap. 

Feb.  1892. 

.  A.  E.  P.  P.,  1874,  iv. 
.  D.  M.  W.,  1898,  xxiv. 


SALOL. 

1.  SAHLI Science    Med.,    April    14, 

1886. 

2.  KUMAGAWA    .   .    .  V.  A.  P.  A.,  1888,  cxiii. 

3.  LESNIK A.  E.  P.  P.,  1888,  xxiv. 

CREOSOTE. 

1.  FREUDENTHAL     .  N.  Y.  M.  R.,  April,  1892. 

2.  ZAWADZKI  .  .  .  .  S.  Jb.,  1896,  ccxlix. 

3.  SAILLET B.  G.  T.,  cxxiii. 

4.  IMBERT Nouveau      Mont.      M6d., 

1892,  i. 

5.  CATILLON  ....  Bull.  Mem.  Soc.  Therap., 

1892. 

6.  HARE U.  M.  M.,  i. 

7.  HOLSCHER  and  SEIFERT  .  B.  K.  W.,    1892, 

xxix. 

8.  BRISSONET    .  .  .  T.  G.,  1893. 

9.  Internal.  Klin.  Rundschau, 

Feb.,  1890. 
10.  BUCHOLZ     ....  A.  E.  P.  P.,  1874,  iv. 


i.  KUPRIANOW 


GUAIACOL. 
.   .   .  Centralb.  f.   Bakter.,  18 


2.  LINOSSIER  and  LANNOIS  .  E.G.  T.,  1894.  Ixiii. 

3.  ESCHLE S.  Jb.,  1896,  ccl. 

4.  GUINARD     .   .   .   .  B.  G.  T.,  1893. 

5.  HESSE D.  M.  W.,  1898. 

6.  HATCH M.  News,  1903,  Ixxxiii. 


CRESOL. 


I.   SCHWYZER 


2.  FRIES 

3.  MAASS 

4.  VONDERGOLDZ  . 

5.  BURGESS  .... 

6.  VAN  ERMENGEN 

7.  PFREUGER  .   .   . 

8.  DELPLANQUE  . 

9.  FRXNKEL  .  .  . 

10.  FAUST 


II.  TOLLENS 


.  N.  Y.  Med.  Monatschrift, 

1904,  vi.  427. 

.  M.  M.  W.,  1904,  No.  16. 
.  D.  A.  K.  M.,  1894,  lii.  446. 
.  N.  Y.  M.  R.,  1892,  xlii.  367. 
.  L.  L.,  1900,  i.  1797. 
.  B.  A.  R.  B.,  1889,  iii.  60. 
.  A.  Pharm.,  1890,  701. 
.  Thesis,  Paris,  1888. 
.  Zeitsch.  f.  Hyg.,  1889. 
.  Jahrsb.       Gesells.        Nat. 

Heilk.,  Dresden,  1895-98. 
.  A.  E.  P.  P.,  lii,  220. 


NAPHTOL. 

i.  SURVEYOR  and  HARLEY  .  B.  M.  J.,  1895,  ii. 

a.  SAHLI Th.  M.,  1887. 

3.  WEEKS N.  Y.  M.  R.,  1889,  xxxvi. 

"3- 
MENTHOL. 

1.  PELLACANI     .  .   .  A.  E.  P.  P.,  xvii.  376. 

2.  GOLDSCHKIDER      .  A.  G.  P.,  l886. 

3.  RUSSELL N.  Y.  M.  R.,  Nov.  1885. 

4.  lOTEYKO C.  R.  S.  B.,  1903,  Iv. 

5.  BISHOP Kansas  City  Med.  Exam., 

1892. 

THYMOL. 
J.  BXLZ     L.  M.  R.,  1878. 


RESORCIN. 

1.  SCHOMACKER    .   .  Thesis,  Dorpat,  1886. 

2.  COHN In.  Dis.,  Berlin,  1882. 

3.  ANDEER Ueber  das  Resorcin,  Wurz- 

burg,    1880;  C.    M.   W., 
1881. 

4.  PLATT A.  J.  M.  S.,  1883,  i. 

5.  MURRELL    .  .   .   .  M.  T.  G.,  1881,  ii. 

6.  LOEFFLER  ....  Thesis,  Wiirzburg,  1889. 

7.  DUJARDIN-BEAUMETZ  .  B.  G.  T.,  ci.  113. 

FORMALDEHYDE. 

1.  Mosso  and  PAOLETTI  .  A.  I.  B.,  1895,  xxiv. 

2.  TRILLAT  ....      La  Formaldehyde,   Paris, 

1896. 

3.  KLUBER M.  M.  W.,  1900,  ii. 

4.  ZORN M.  M.  W.,  1900,  ii. 

5.  TUNNICLIFFE  and  ROSENHEIM  .  Cb.  P.,  1901, 

xv.  2. 

6.  FOULKRTON  .    .    .  L.  L.,  1899,  ii. 

7.  SLATER  and   RIDKAL  .  Dis.  and  Preserv.  of 

Food,  1903,  309. 

8.  RAVENEL  and  GILLILAND  .  U.  P.  M.  B.,  April, 

1903- 

9.  KOCH A.  J.  P.,  1902,  vi. 

10.  VAN    ERMENGEN    and    SUGG  .  A.    Pharm., 

1895,  i- 

11.  HORTON M.  News,  August,  1896. 

12.  HERZOG Cb.  B.,  xxxiv.  1903. 

13.  ORTH B.  K.  W.,  1896,  xxxiii. 

14-  B.  M.  J.,  1903,  i. 

15-  B.  M.  J.,  1902,  ii. 

16.  BRICKDALE    .  .  .  L.  L.,  1903,  i. 

17.  PARK N.  Y.  M.  J.,  Ixxvii. 

18.  BARROWS    .  .   .   .  N.  Y.  M.  J.,  Ixxvii. 

19.  HONAN N.  Y.  M.  T.,  1903. 


BENZOIN. 


1.  SELIGSOHN    .  . 

2.  URE 

3.  MEISSNER  and 


4.  GRUBE  . 

5.  GARROD 

6.  KELLER 


7.  VIRCHOW    . 

8.  ASHHURST  . 

9.  DOUGALL      . 

10.  SALKOWSKI 

11.  BUCHOLZ    . 

12.  FLECK  . 


13.  SENATOR    .   . 

14- 

15.  LEWANDOSKY 


.  Chem.  Centralb.,  1861. 
.  M.  C.  Tr.,  1841,  xxix.  30. 
SHEPARD  .  Untersuch.    iiber 

das   Entstehen  der  Hip- 

pursaure,  Hanover,  1866. 
.  Cb.  C.,  1876,  777. 
.  L.  L.,  Nov.  1844. 
.  Ann.  der  Chem.  u.  Pharm., 

1842,  xliii. 
.  Z.  P.  C.,  vi. 
.  P.  M.  J.,  Feb.  24,  1900. 
.  M.  T.  G.,  1872,  i. 
.  B.  K.  W.,  1875,  297. 
.  A.  E.  P.  P.,  iv. 
.  Benzoesaiire,  etc.,  Munich, 

1875- 
.  Allg.  Wien.  Med.  Zeitung, 

1876,  xxiii. 
P.  M.  T.,  iv. 
.  Z.  K.  M.,  1903,  xl. 


DISINFECTANTS. 


877 


REFERENCES.— Continued. 


CINNAMIC    ACID. 
1.  LANDHRER  .   .   .   .  M.  M.  W.,  xxxv. 
a.  ROBINSON  ....  M.  A.,  1902. 

SULPHUROUS  ACID. 

i.  PFEIFFER   ....  Sajous's  Annual,  1891. 

FLUORIDES. 

1.  TAPPEINER    .   .   .  A.  E.  P.  P.,  xxvii. 

2.  TISCHER  and  BEDDIES  .  A.  R.,  1898. 

3.  BINZ V.  C.  M.,  1891,  ii. 

4.  GORL M.  M.  W.,  1899. 

BORIC  ACID. 

1.  DUJARDIN   ....  Union  M6d.  du  Nord-Est, 

Nov.  1891. 

2.  DUMAS  and    SCHNATZLES  .  Pharm.   Journ., 

April,  1874. 

3.  BUCHOLZ     .  .  .  .  A.  E.  P.  P.,  iv. 

4.  WALB C.  K.  M.,  1882,  iii.  529. 

5.  STERNBHRG    .  .   .  A.  J.  M.  S.,  Ixxxiv.  321. 


6.  ANDREWS    ....  Chicago  Med.  Exam.,  1889, 

Iviii. 

7.  CHITTENDEN  and  GIES  .  A.  J.  P.,  i.  39. 

8.  STRAUB S.  Jb.,  280. 

9.  WELCH N.  Y.  M.  R.,  1888,  xxxiv. 

10.  MODODEWKOW  .   .  St.  L.  C.  R.,  1881. 

11.  HOGNER S.  Jb.,  202. 

12.  ROSENTHAL   .  .  .  Allg.     Wien.    Med.    Ztg., 

Jan.  1884. 

13.  GREENS B.  M.  S.  J.,  ciii.  209. 

14.  FOLSOM B.  M.  S.  J.,  Feb.  18,  1886. 

15.  MAASS Th.  M.,  1903,  iii. 

16.  GRUBKR H.  S.  Jb.,  1879. 

17.  PLAUT Thesis,  Wiirzburg,  1889. 

18.  FERE Semaine  M6d.,  1894,  xiv. 

19.  HARRINGTON    .   .  A.  J.  M.  S.,  cxxviii.  418. 

PRACTICAL  DISINFECTION. 

1.  ABBOTT Tr.  I.  C.  C.,  1893. 

2.  WOOD,  JR U.  P.  M.  B.,  1905. 


APPENDIX. 


Pound, 
Ounce, 
Drachm, 
Scruple, 

Grain, 


APOTHECARIES'  WEIGHT-APOTHECARIES'  MEASURE. 


FORMERLY   OFFICIAL    IN    THE    UNITED    STATES    PHARHACOPCEIA. 


12  Ounces. 

8  Drachms. 

3  Scruples. 
20  Grains. 

1  Grain. 


Gallon, 

Pint, 

Fluidounce, 

Fluidrachm. 

Minim, 


"I 


8  Pints. 
16  Fluidounces. 

8  Fluidrachuis. 
60  Minims. 

1  Minim. 


WEIGHTS  AND  MEASURES  OF  THE  METRICAL  OR  FRENCH  SYSTEM. 

NOW   OFFICIAL    IN    THE   UNITED   STATES    PHARMACOPEIA. 


MEASURES   OF   LENGTH. 

One  Myriametre  =  10,000  Metres. 

One  Kilometre  =     1,000  Metres. 

One  Hectometre  =        100  Metres. 

One  Decametre  =          10  Metres. 

One  METRE  =  the  ten-millionth  part  of  a  quarter  of  the  meridian  of  the  earth. 

One  Decimetre  =  the  tenth  part  of  one  Metre  or  0.1  Metre. 

One  Centimetre  =  the  hunredth  part  of  one  Metre,  or  0.01  Metre;  written  Cm. 

One  Millimetre  =  the  thousandth  part  of  one  Metre,  or  0.001  Metre;  written  Mm. 

WEIGHTS. 

One  Myriagramme  =  10,000  Grammes. 

One  Kilogramme     =     1,000  Grammes. 

One  Hectogramme  =        100  Grammes. 

One  Decagramme    =          10  Grammes. 

One  GRAMME        =  the  weight  of  a  cubic  Centimetre  of  Water  at  4°  C. ;  written  Gm. 

One  Decigramme     =  the  tenth  part  of  one  gramme,  or  0.1  Gramme. 

One  Centigramme    =  the  hundredth  part  of  one  Gramme,  or  0.01  Gramme. 

One  Milligramme    =  the  thousandth  part  of  one  Gramme,  or  0.001  Gramme. 


MEASURES   OF   CAPACITY. 

One  Myrialitre  =10  cubic  Metres,  or  the  measure  of  10  Milliers  of  Water. 

One  Kilolitre  =  1  cubic  Metre,  or  the  measure  of  1  Millier  of  Water. 

One  Hectolitre  =100  cubic  Decimetres,  or  the  measure  of  1  Quintal  of  Water. 

One  Decalitre  =  10  cubic  Decimetres,  or  the  measure  of  1  Myriagramme  of  Water. 

One  LITRE  =  1  cubic  Decimetre,  or  the  measure  of  1  Kilogramme  of  Water. 

One  Decilitre  =  100  cubic  Centimetres,  or  the  measure  of  1  Hectogramme  of  Water. 

One  Centilitre  =  10  cubic  centimetres,  or  the  measure  of  1  Decagramme  of  Water. 

One  Millitre  =  1  cubic  Centimetre,  or  the  measure  of  1  Gramme  of  Water. 

879 


88o 


APPENDIX. 


RELATION  OF  APOTHECARIES'  WEIGHTS  AND  MEASURES  TO  EACH 

OTHER. 


One  Pound 
One  Ounce 
One  Drachm 
One  Scruple 
One  Grain 
One  Gallon 
One  Pint 
One  Fluidounce 
One  Fluidrachm 
One  Minim 


In  diftilled  water  at  the  temperature  of  60°. 

0.7900031  Pint  = 

1 .0533376  Fluidonnces  = 

1.0533376  Fluidrachms  = 


10.1265427  Pounds 
1.2668178  Pounds 
0.9493633  Ounce 
0.9493633  Drachm 


6067.22.S 

505.6019 

63.2002 

21.0667 

1.0533 

5S328.8862 

7291.1107 

455.6944 

56.9618 

0.9493 


Minims. 
Minims. 
Minims. 
Minims. 
Minims. 
Grains. 
Grains. 
Grains. 
Grains. 
Grain. 


RELATION  OF  APOTHECARIES'  OR  WINE  MEASURE  TO  CUBIC  MEASURE. 


One  Gallon 

One  Pint 

One  Fluidounce 


=  231.  Cubic  Inches. 

=     28.875       Cubic  Inches. 
=       1.80468  Cubic  Inches. 


One  Fluidrachm 
One  Minim 


0.22558  Cubic  Inch. 
0.00375  Cubic  Inch. 


RELATION  OF  APOTHECARIES'  WEIGHTS  TO  METRICAL  WEIGHTS. 


Fraction  of 

a  grain  in 

Drachmt,  Ounctt,  and  Povndt  in 

Milligramme*. 
Grain.                 Milligrammes. 

Grain*  in  equivalent  metrical 
weight*. 

equivalent  metrical  weight*. 
Drachms.                Grammes. 

A 

"" 

1.012 
1.079 

Grains. 
1 

Centigrammes. 
6.479 

1 
2 

_ 

3.887 
7.775 

£ 

- 

1.295 

2 

Decigrammes. 
1.295 

I 

_ 

Decagramme*. 
1.166 

A 

M 

1.349 

I 

_ 

1.943 

4 

tm 

1.555 

A 

— 

1.619 

4 



2.591 

5 

m 

1.943 

40 

1  799 

5 

_ 

3.239 

6 

»• 

2.332 

»l 

*" 

'I  UP 

3.887 

7 

B 

2.721 

A 

= 

2.159 

7 

4.535 

Ounces. 

A 

A 
A 

- 

2.591 
2.699 
3.239 
4.049 

8 
9 
10 
12 
15 

_ 

5.183 
5.831 
6.479 
7.775 
9.798 

) 

4 
5 

- 

3.1103 
6.2206 
9.3309 
Hectogrammes. 
1.2441 
1.5551 

JL 

_ 

4.319 

Grammes. 

A 

_ 

MM 

16 

AA 

- 

.036 

OQFL 

6 

7 

~; 

2.1772 

A 

- 

6.479 

XV 
24 

™ 

•zy* 
.555 

8 

2.4882 

_ 

8.098 

25 



.619 

9 

2.7992 

10 

3.1103 

- 

10.798 

30 
40 

= 

.943 
2.591 

11 

- 

3.4213 

•B 

12.958 

Pounds. 

- 

16.197 

50 

60 

_ 

3^887 

1 

2 

3.7324 
7.4648 

• 

21.597 

Kilogrammes. 

• 

32.395 

3 

- 

1.1197 

APPENDIX 


ttl 


RELATION  OF  METRICAL  WEIGHTS  TO  APOTHECARIES'  WEIGH*. 


.•154 
- 

.M«3 
J«17 

.•771 
.•92C 


.1254 


.1>43 


.«17S 

.7717 


1.2347 
L 


1.M3 
3jM< 

4.S3* 

-  -    ' 


12JU7 


i 
I 
I 

I 

A 


A 

i 

U 
H 


3 
44 
' 
r| 

11 
14 


gr.  XT. 


31- 


Si. 


5«oT. 

fti  3ri|. 


( ft  xrrL 


882 


APPENDIX. 


TABLE  OF  THE  PROPORTION   BY  MEASURE  OF  ALCOHOL  (SP. 
0.825)    CONTAINED    IN   ONE   HUNDRED    PARTS  OF 
DIFFERENT  WINES,   ETC.* 

Lisa  (mean) 25.41 

Raisin  wine  (mean)....  25.12 
Marsala  [Sicily  ma- 
deira] (mean)...  25.09 

strongest  (J.) 21.10 

weakest  (J.) 19.90 

Port,  strongest 25.83 

mean  22.96 

weakest 19.00 

strongest  (C.) 20.49 

mean  (C.) 18.68 

weakest  (C.) 16.80 

strongest  (J.)  23.20 

weakest  (J.) 20.70 

White  port  (C.) 17.22 

Madeira,  strongest 24.42 

mean  22.27 

weakest 19.24 

strongest  (C.) 20.35 

strongest  (J.) 19.70 

weakest  (J.) 19.00 

Sercial  madeira 21.40 

Ditto  (C.) 18.50 

Sherry,  strongest 19.81 

mean 19.17 

weakest 18.25 

strongest  (C.) 19.31 

mean  (C.) 18.47 

weakest  (C.) 16.96 

Amontillado  (C.)..  15.18 

strongest  (J.) 24.70 

weakest   (J.) 15.40 

Teneriffe  ...  ..   19.79 


Teneriffe  (C.)  16.61 

Colares 19.75 

Lachryma  Christi 19.70 

White  Constantia 19.75 

Red  Constantia 18.92 

Lisbon 18.94 

Ditto  (C.) 19.09 

Bucellas 18.49 

Red  madeira  (mean)...  20.35 

Cape  muscat 18.25 

Cape  madeira  (mean)..  20.51 

Grape  wine 18.11 

Calcavella  (mean) 18.65 

Vidonia 19.25 

Alba  flora 17.26 

Zante 17.05 

Malaga 17.26 

White  Hermitage 17.43 

Roussillon  (mean) 18.13 

Claret  (strongest) 17.11 

mean  15.10 

weakest 12.91 

ditto  (F.) 14.73 

vin-ordinaire  (C.).  10.42 
Chateau-  Latour, 

1825   (C.) 

first-growth,  1811 

(C.) 

strongest  (J.) 

weakest   (J.) 


9.38 

9.32 

11.10 

9.10 


Malmsey  madeira 16.40 

Ditto  (C.) 15.60 


Lunel 

Ditto  (F.) 

Shiraz  

Ditto  (C.) 

Syracuse 

Sauterne 

Burgundy   (mean) 

strongest  (J.) 

weakest  (J.) 

Hock   (mean)  

strongest  (J.) 

weakest  (J.) 

Nice 

Barsac 

Tont 

Champagne  (mean) 

Ditto  (F.) 

Ditto,  strongest  (J.).... 

weakest  (J.) 

Red  hermitage 

Vin  de  Grave  (mean)... 
Frontignac    (Rives 

Altes)..... 

Ditto  (C.) ... 

C6ter6tie 

Tokay  

Rudesheimer,  first 

quality  (C.) 

inferior  (C.) 

Hambacher,  first 

quality  (C.) 

Catawba  (Stearns) 


GR. 


15.52 
18.10 
15.52 
15.56 
15.28 
14.22 
14.57 
13.20 
10.10 
12.08 
13.00 
9.50 
14.63 
13.86 
13.30 
12.61 
12.20 
14.80 
14.10 
12.32 
13.37 

12.79 
12.29 
12.32 


10.14 
8.35 


8.88 
8  to  11 


Cider,  highest  average.  9.87 

lowest  average 5.21 

Perry,  average  of  four 

samples 7.26 

Mead 7.32 

Ale  (Burton) 8.88 


Ale  (Edinburgh) ...  6.20 

Ale  (Dorchester) 5.56 

Brown  stout 6.80 

London  porter 4.20 

London  small  beer 1.28 


Brandy 53.39 

Rum 53.68 

Gin 51.60 

Scotch  whisky 54.32 

Irish  whisky 53.90 


*  The  analyses  whose  results  are  given  in  this  table  were  mostly  made  by  Mr.  Brande. 
When  no  mark  is  attached,  the  quotation  is  upon  his  authority.  When  the  mark  (F.)  is 
added,  the  analysis  was  made  by  Julia-Fontenelle ;  (C.),  by  Professor  Christison ;  (J.),  by 
Dr.  H.  Bence  Jones. 


APPENDIX. 


883 


1,  M.  corrugator  supercil. ;  2,  M.  com" 
pressor  nasi  et  pyramidal,  nasi ;  3,  M- 
orbicular,  palpebr. ;  4,  M.  levator  lab- 
sup,  alaeque  nasi ;  5,  M.  levator  lab.  sup- 
§ropr. ;  6,  M.  zygomatic.  minor ;  7,  M. 
ilatat.narium  ant.  et  post.:  8,  M.  zygo- 
matic. major;  9,  M.  orbicularis  oris; 
10,  Ram.  comm.  pro  Mm.  triangular, 
et  levator  menti ;  11,  M.  levator  menti; 
1'2,  M.quadratus  menti;  13,  M.triangu- 
laris  menti;  14,  Ram.  subcutan.  colli 
N.  facial. ;  15,  Ram.  cervical,  pro  Pla- 
tysmat.;  16,  M.  stern  o-hyoideus ;  17,  M. 
omo-hyoideus ;  18,  M.  sterno-tbyroi- 
deus;  19,  M.  sterno-hyoideus ;  20,  M. 
frontalis  :  21,  Mm.  attrahens  et  attol- 
lens  auriculae ;  22,  Mm.  retrahens  et 
attoll.  auriculae ;  23,  M.  occipitalis ; 
24,  Nerv.  facialis;  25,  Ram.  auricular, 
post.  prof.  N.  facialis;  26,  M.  stylo-hyoi- 
deus;  27,  M.  digastricus;  28,  Ram.  buc- 
cales,  N.  facialis;  29,  M.  splenius  capi- 
tis  ;  30,  Ram.  subcutan.  maxill.  infer.; 
31,  Ram.ext.  N.  accessorii  Willisii;  32, 
M.  sterno-cleido-mastoideus ;  33,  M. 
cucullaris ;  34,  M.  sterno-cleido-mas- 
toideus ;  35,  M.  levator  anguli  scap- 
ulae ;  36,  N.  thoracic,  post.  (Mm.  rhom- 
boidei) ;  37,  N.  phremcus ;  38,  M.  omo- 
hyoid  ;  39,  N.  thoracic,  lateral.  (M. 
serrat.  magn.) ;  40,  N.  axillaris;  41, 
Ram.  plex.  brachialis  (N.  musculo- 
cutan.,  pars  N.  mediani) ;  42,  N.  tho- 
racic, ant.  (M.  pectorales). 


M.  rectus   ab- 

dominis. 
(Nervi  intercos- 
tal es      abdomi-  • 
nales.) 


M.    serratus    Mag- 
nus. 
M.latissimus  dorsi. 


M.  obliquus  ab- 

dominis     exter- 

nus. 

(Nervi  intercos- 

tales      abdomi- 

nales.) 


M.  trans  versus  ab- 
dominis. 


$84 


APPENDIX. 


N  cruralis 

X.  obturatorius. 
M.sartorius 


M.  adductor  lorigus 

Kami  N.  cruralis  pro  M.  quadrici- 
pite. 

M.  cruralis 

Kami  N.  cruralis  pro  M.  vasto  in- 
terno.... 


M.  tensor  vaginae femoris.  (Kami 
N.  glutaei  superioris.) 


M.  tensor  vagina:  femoris.  (Kami 
N.  cruralis.) 


M.  rectus  femoris. 

M.  vastus  externus. 
M.  vastus  externus. 


M.  peroneus  longus. 
M.  tibialis  anticus  ... 


M.  extensor  hallucis  longus 


Kami  N.  peronei  prof,  pro  M 
extensore  digitorum  brevi 


Mm.  interossei  pedis  dorsales.  •<  —-' 


N.  peroneus. 

M.  gastrocnemius  externus. 

M.  solcus. 

M.  extensor  digitorum  longus, 


M.  ]>eronous  brevis. 
M.  solcus. 

....  M.  flexor  hallucis  longus. 


..M.  extensor  digitorum  brevis. 


M.    abductor    digiti    minimi 
pedis. 


APPENDIX. 


88=; 


Kami  inferiores  N.  glutati  inferioris 

pro  M.  glutseo  maximo 

N.  ischiadicus 

M.  biceps  (caput  longum) 


M.  biceps  (caput  breve) 


N.  tibialis 

N.  peroneus 

M.  gastrocnemius  externus 


M.  soleus. 


M.  gastrocnemius  interims 
M.  soleus 


M.  flexor  digitorum  longus 


N.  tibialis. 


M.  abductor  hallucis 


M.  adductor  magnus. 

....M.  semitendinosus. 
•...M.  semimembranosus. 


M.  gastrocnemius, 


886 


APPENDIX. 


N.  Museulo-cutaneus.       M.  biceps. 


N.  musculo- Caput  in-     N.  Media-    ;        N.  ulnaris.  Kami  N.  mediant 
cutaneus.    ternus  M.        nus.    M.  brachialis  pro  M.  pronatore 

tricipitis.  internus.  radii  terete. 


Ranli  Nervi  mediani  pro  M.  pro 
natore  radii  terete 


M.  palmaris  longus.. 


M.  ulnaris  internus. 


M.  flexor   digitorum   sublimis 
(digitt.  II  et  III.) 


N.  ulnaris 

M.  flexor    digitorum   sublimis 
(digitt.  indicia  et  minim) 


Kami  volar.  prof.  Nervi  ulnaris- 
M.  palmaris  brevis 

M.  abductor  digiti  minimi 

M.  flexor  digitiminimi 

M.  opponens  digiti  minimi 

Mm.  lumbricales  II,  III  et  iv| 


.M.  radialis  internus. 
M.  flexor  digitorum  profundus. 

M.  flexor  digitorum  sublimia. 


M.  flexor  pollicis  longus. 
N.  medianus. 


M.  abductor  pollicis  brevie. 
M.  opponens  pollicis. 

M.  flexor  pollicis  brevifl. 
M.  adductor  pollicis. 
M.  lumbricalis  I. 


APPENDIX. 


887 


Caput  externus  M.  tricipitis 


N.  radialis 

M.  brachialis  internus 


M.  supinator  longus 

M.  radialis  externus  longus 

M.  radialis  externus  brevis 


M.  supinator  longus 
M.  radialis  externus 


us  longus 


M.  radialis  externus  brevflf 


M.  extensor  digitorum  communist 

M.  extensor  indicis  proprius 

M.  extensor  indicis  proprius  et  M. 

abductor  pollicis  longus 

M.  abductor  pollicis  longus 


M.  extensor  pollicis  brevis 
M.  flexor  pollicis  longus 


M.  interosseus  dorsalis  I 
M.  interosseus  dorsalis  II 
M.  interosseus  dorsalis  III 


M.  ulnaris  externus. 


M.  extensor  digiti  minimi  pro- 
prius. 


M.  extensor  indicis  proprius. 
M.  extensor  pollicis  longus. 


M.  abductor  digiti  minimi. 
M.  interosseus  dorsalis  IV. 


INDEX  OF  DISEASES. 


Abscess . 

alcohol,   to  support  system  by  its  food  value  also  as  heart  stimulant,   306. 

bismuth  oxyiodogallate ,  glycerin  solution  injected  into  cold  abscesses,  426. 

boric  acid,  a  feeble  antiseptic,  869. 

formaldehyde,  employed  in  tuberculous  cases,  859. 

hydrogen  dioxide,  as  a  disinfectant  and  cleansing  agent,  829. 

iodoform,  in  tuberculous  forms,  513. 

menthol,  a  saturated  alcoholic  solution  painted  on  superficial  abscesses,  852. 

naphtol,  solution  for  injection  into  abscesses,  851. 

potassium  permanganate,   as  a  cleansing  disinfectant  when  fetid  discharges, 

827. 
tannic  acid,  when  excessive  secretion,  404. 

Acidity  of  Stomach : 

ammonia,  stimulant,  promptly  acting,  too  irritating  to  be  used  in  inflamma- 
tory conditions   282. 

magnesia,  antacid  and  gently  laxative,  654. 
soda,  the  most  generally  serviceable  antacid,  800. 

Acne: 

arsenic,  valuable  alterative,  especially  in  chronic  cases,  474. 

calcium  sulphide,  credited  with  peculiar  alterative  action,  631. 

ichthyol,  supposed  to  possess  the  power  of  penetrating  the  skin  and  exercising 

a  local  alterative  action,  527. 

iodine,  powerfully  antiseptic  but  of  doubtful  value,  504. 
oil  of  cajuput,  stimulant  and  parasiticide,  629. 
phosphorus,  used  internally  in  cases  with  poor  nutrition,  461. 
solution  of  mercuric  nitrate,  caustic,  used  to  destroy  pustules,  780. 

Aconite  Poisoning : 

alcohol,  a  rapidly  acting  cardiac  stimulant,  306. 

digitalis,  a  powerful  stimulant  to  the  heart,  but  slowly  acting,  327. 

Actinom ycosis : 

potassium  iodide,  only  drug  likely  to  be  of  service  internally,  506. 
Addison's  Disease : 

suprarenal  capsule,  supplies  lacking  secretions,  use  must  be  continued  indefi- 
nitely, 542. 

After  Pains : 

antipyrine,  608. 

Ague: 

See  MALARIA. 

Alcoholism : 

apomorphine,  emetic  and  sedative,  640. 
capsicum,   for  alcoholic  gastritis,  629. 

gold  and  sodium  chloride,  supposed  to  exercise  a  specific  effect  on  central  ner- 
vous system  in  alcoholic  habit,  497. 
strychnine,  valuable  in  chronic  alcoholism,  222. 
treatment  of  acute  alcoholism,  310. 

Alopecia : 

arsenic,  in  atrophic  variety,  474. 
pilocarpine,  726. 

889 


890  INDEX   OF    DISEASES. 

Amaurosis : 

See  BLINDNESS. 

Ambl yopia : 

strychnine,  especially  useful  in  tobacco  or  alcoholic  cases,  221. 
Amenorrhoea : 

aloes,  cathartic,  tends  to  increase  pelvic  congestion,  enters  into  several  em- 

menagogue  combinations,  665. 

apiol,  to  be  given  for  a    week  previous  to  expected  menses,  744 
cantharides,    stimulating  to  uterine  mucous  membranes,  742. 
clave  tea,  useful  where  menses  suppressed  by  "cold",  627. 
cotton  root,  stimulant  to  uterus,  764. 

Dewees's  emmenagogue  mixture,  a  valuable  routine  combination,  742. 
diaphoretics,  of  service  in  acute  suppressions,  719. 
emmenagogues,  their  limitations  and  uses,  741. 
ginger,  may  be  given  in  form  of  infusion,  628. 

Griffith's  mixture  (mistura  ferri  composita),  employed  in  anaemic  cases,  449,  741 
guaiac,  an  ingredient  of  Dewees's  mixture,  449,  741. 
iron,  useful  in  anaemic  cases,  741. 
myrrh,  an  ingredient  of  Griffith's  mixture,  741. 
oil  of  pennyroyal,  feeble,  743. 

oxalic  acid,  active  but  somewhat  dangerous,  398. 
pills  of  aloes  and  myrrh,  666. 

potassium  permanganate,  not  very  valuable,  but  sometimes  of  service,  741. 
saccharated  ferrous  carbonate,  a  useful  form  of  administering  iron,  449. 
santonin,  has  been  recommended  in  acute   menstrual  suppression,  809. 
sumbul,  useful  in  cases  associated  with  nervous  symptoms,  80. 
turpentine,  when  there  is  much  relaxation,  710. 

Ammonia  Poisoning : 

treatment,  282. 

Ammoniacal  Urine  : 
See  CYSTITIS. 

Anaemia : 

See  CHLOROSIS  and  PERNICIOUS  ANAEMIA. 

Anaesthesia,  Accidents  in : 

ammonia,  rapidly  acting  heart  stimulant,  281. 
artificial  respiration,  a  most  important  factor,  115. 
cardiac  massage,  may  be  tried  in  desperate  cases,  115. 
treatment  of,  113. 

Aneurism : 

digitalis,  useful  where  heart  is  very  feeble,  but  must  be  employed  with  great 

caution  on  account  of  danger  of  rupture,  326. 

ergot,  recommended  to  be  injected  in  the  immediate  vicinity,  752. 
gelatin,  promotes  coagulation  of  the  blood,  533. 
potassium  iodide,  largely  employed,  but  there  is  no  explanation  of  the  manner 

in  which  it  benefits,  506. 

Angina : 

See  SORE  THROAT. 

Angina  Pectoris: 

amyl  nitrite,  very  prompt  and  efficacious,  to  be  used  during  the  attack,  258. 
erythrol  tetranitrate ,  acts  like  nitroglycerin  but  more  lasting,  262. 
mtroglycerin,  similar  in  its  action  to  amyl  nitrite,  more  persistent,  261. 

Anorexia : 

bitters,  stimulate  the  flow  of  gastric  juice,  also  probably  increase  appetite 

through  their  bitter  taste,  621. 
orexine,  a  synthetic  bitter,  highly  lauded,  625. 
quinine,  acts  as  a  bitter,  but  also  has  effect  on  metabolism,  572. 


INDEX   OF   DISEASES.  891 

Anthrax  : 

phenol,  to  be  injected  into  the  ulcer,  838. 

Aortic  Lesions : 

See  ENDOCARDITIS. 

Aphthous  Stomatitis : 

See  STOMATITIS. 

Apoplexy  : 

croton  oil,  useful  as  a  purgative  where  patient  cannot  swallow;  also  acts  as 
revulsant,  676. 

emetics,  not  useful  in  true  apoplexy,  but  in  those  forms  of  coma  resembling 
apoplexy.  633. 

nitro-glycerin,  useful  to  advert  threatened  apoplexy  by  dilating  the  blood- 
vessels. 262. 

Arsenic  Poisoning  : 

dialyzed  iron,  less  useful  than  the  freshly  precipitated  hydrate,  but  may  be  of 

service  in  emergency,  451. 
ferric  hydrate,  may  be  prepared  extemporaneously  by  adding  any  alkali  to  a 

solution  of  ferric  sulphate  or  chloride,  448. 
Jerri  hydroxidum  cum  magnesii  oxido,  chemical  antidote,  448. 
treatment,  480. 

Ascites : 

See  DROPSY. 

Asthenopia : 

strychnine,  acts  almost  specifically,  222. 

Asthma : 

Symptomatic  Treatment: 

amyl  nitrite,  very  prompt  and  powerful,  used  by  inhalation  during  attack, 
258. 

anesthetics,  sometimes  useful  during  attack,  82. 

atropine,  may  be  given  hypodermically  in  large  doses,  probably  less  useful 
than  the  burning  belladonna,  180. 

belladonna,  useful,  especially  to  be  burned  and  vapors  inhaled,  180. 

chloral,  occasionally  but  not  generally  useful,  152. 

chloralformamid,  recommended  in  asthma  depending  upon  cardiac  disease, 
165. 

ether,  sometimes  of  service,  91. 

ethyl  nitrite,  probably  of  less  value  than  amyl  nitrite,  may  be  employed  in 
similar  cases,  260. 

grindelia,  useful  as  an  expectorant,  may  be  added  to  a  burning  powder,  736. 

heroin,  especially  useful  in  secondary  asthma,  acts  by  lessening  irritability 
of  respiratory  centers,  145. 

lobelia,  may  be  used  as  an  expectorant,  also  in  emetic  doses  during  parox- 
ysms, 263,  733. 

nitroglycerin,  maybe  used  hypodermically  in  the  place  of  amyl  nitrite,  261. 

stramonium,   acts  like  belladonna,  used  especially  for  making  cigarettes  or 

burning  powders,  185. 
Constitutional  Treatment: 

antipyrine,  lessens  irritability  of  nervous  system,  608. 

arsenic,  may  be  used  either  locally  or  internally,  474. 

aspidosperma,  acts  upon  respiratory  center,  278. 

atropine,  may  be  used  as  a  preventative  of  spasmodic  asthma,  180. 

hyoscine,  similar  to  atropine  in  its  effect,  more  sedative,  189. 

potassium  iodide,  one  of  the  most  valuable  drugs  known  between  the  par- 
oxysms,   506. 

spartein,  may  be  employed  in  asthma  depending  upon  cardiac  lesions,  350. 

suprarenal  capsules,  recommended  to  be  used  internally,  543. 

thymus  gland,  has  been  recommended,  but  of  doubtful  utility,  543. 


892  INDEX   OF   DISEASES. 

Atheroma : 

digitalis,  useful  in  heart  failure,  must  be  employed  with  caution,  326. 

nitre/glycerin,  used  to  reduce  tension  in  arteries,  261. 

sodium  nitrite,  similar  in  its  effect  to  nitroglycerin,  but  more  persistent,  261. 

Atropine  Poisoning: 

pilocarpine,  physiological  antagonist  to  atropine,  727. 
treatment  of,  184. 

B 
Biliousness : 

emetics,  mechanically  relieve  portal  congestions,  633. 

ipecacuanha,  has  a  special  action  on  the  liver,  638. 

mercury,  in  the  form  of  calomel  or  blue-mass,  the  most  generally  valuable 

remedy  in  acute  cases,  662. 

nitro-hydrochloric  acid,  of  service  especially  in  chronic  cases,  456. 
oxgall,  is  the  most  powerful  stimulant  to  hepatic  secretion  known,  653. 
podophyllum,  sometimes  called  "vegetable  mercury"  on  account  of  its  effect 

on  the  liver,  673. 

potassium  acetate  and  citrate,  of  service  in  chronic  biliousness,  693. 
taraxacum,  of  doubtful  value,  530. 

Bites: 

See  HYDROPHOBIA;  also  SNAKE-BITES. 

Black-water  Fever: 

methylene-blue,  is  destructive  to  malarial  parasite,  but  not  irritant  to  the 
kidney,  581. 

Bladder,  Irritable: 

See  CYSTITIS. 

Bladder,  Tuberculosis  of: 

guaiacol,  dissolved  in  olive  oil  and  injected  into  bladder,  846. 
Blindness : 
santonin,  809. 
strychnine,  especially  useful  in  toxic  cases  as  alcohol  or  tobacco,  221. 

Boils: 

calcium  sulphide,  useful  where  successive  crops  of  boils,  659. 

infiltration  anesthesia,  to  open  boils,  120. 

kaolin,  as  substitute  for  flaxseed  poultice,  793. 

menthol,    saturated    alcoholic    solution    painted    over    area   will     sometimes 

abort,   852. 
phosphorus,  as  general  tonic  and  alterative,  461. 

Bone  Diseases: 

carbolic  acid,  injected  deeply,  838. 

iodine,  internally  in  scrofulous  cases,  503. 

phosphorus,  has  a  stimulant  action  on  growth  of  bone,  467. 

Brain  Softening: 

phosphorus,  sometimes  of  benefit,  461. 
Bright'*  Disease: 

antipyrine,  609. 

apocynum,  to  eliminate  dropsical  effusions,  334. 

caffeine,  to  evacuate  dropsy,  to  be  used  only  very  cautiously  if  at  all  in  acute 

cases,  348. 

calomel,  one  of  the  most  powerful  diuretics  known,  683. 
diaphoretics,  aid  in  the  excretion    of  waste  products  through  the  skin,  717. 
digitalis,  in  acute  suppression  may  be  applied  externally  with  benefit,  684. 
diuretics,  679. 
gattic  acid,  to  diminish  excessive     secretion  in  chronic  interstitial  nephritis, 

406. 
hypodermoclysis,  in  acute  irritation  of  kidneys  or  suppression,  679. 


INDEX   OF    DISEASES.  893 

pilocarpine,  may  be  used  to  produce  sweating,  also  to  stimulate  kidney  in 

acute  suppression,  7  2  6. 

potassium  bitartrate,  of  value  in  acute  nephritis,  693. 
strontium  lactate,  claimed  to  diminish  the  amount  of  albumin,  but  of  doubtful 

value,    704. 

strophanthus,  more  stimulant  to  kidneys  than  digitalis.  338 
tannalbin,  in  cases  where  large  amounts  of  albumin,  405. 
theobromine,  may  be  employed  in  both  acute  and  chronic  cases  when  secretion 

is  insufficient,  685. 

theocin,  a  synthetic  alkaloid  of  value  in  dropsical  cases,  685 
thyroid  extract  538 

tincture  of  ferric  chloride,  much  employed  in  chronic  cases,  449. 
water,  in  acute    irritations  large  draughts  of  water  often  valuable,  678. 

Bronchitis,  Acute: 

ammonium  chloride,  somewhat  stimulant,  use  after  secretion  is  established, 

735- 

antimony,  to  be  employed  only  in  robust  or  sthenic  patients,  364 
apomorphine  hydrochloride ,  encourages  the  establishment  of    secretion,  642. 
Brown  mixture,  demulcent  for  mild  cases,  784. 
codeine,  as  a  cough  sedative,  142. 
demulcents,  782. 

eucalyptus,  used  when  there  is  free  secretion,  584. 
garlic,  sometimes  useful  in  feeble  infants,  737. 
heroine,  a  very  valuable  cough  sedative,  145. 
ipecacuanha,  increases  expectoration,  use  in  early  stages,  731. 
lobelia,  of  service  when  there  is  tendency  to  asthmatic  spasms,  263. 
oil  of  sandal-wood,  in  the  latter  stages,  708,  738. 
opium,  cough  sedative,  avoid  where  expectoration  is  profuse,  134. 
potassium  citrate,  increases  secretion,  especially  serviceable  in  early  stages, 

733- 

senega,  739. 

sulpnuretted  hydrogen,  useful  where  free  expectoration,  740. 
tar,  used  only  in  advanced  stages,  737. 
terebene,  stimulating  expectorant,  use  in  later  stages,  738. 
terpin  hydrate,  of  service  after  secretion  has  been  established,  738. 
turpentine  stupes,  act  by  counter-irritation,  710. 

Bronchitis,  Chronic : 

ammoniac,  739. 

ammonium  chloride,  employed  where  expectoration  is  not  profuse,  735. 

arsenic,  may  be  used  either  internally  or  in  form  of  cigarettes,  474,  730. 

asafetida,  of  service  in  the  aged,  76. 

aspidosperma,  to  relieve  dyspnoea,  278. 

balsam  of  Tolu,  736. 

benzoic  acid,  a  valuable  remedy,  863. 

Burgundy  pitch,  externally  as  a  counterirritant,  775. 

cimtcifuga,  79. 

compound  tincture  of  benzoin,  may  be  used  either  internally  but  especially  by 

inhalation,  863. 

copaiba,  in  cases  with  free  muco-purulent  expectoration,  713. 
creosote,  one  of  the  most  active  stimulating  expectorants,  845. 
creosote  carbonate,  supposed  to  be  less  irritating  to  the  stomach  than  creosote, 

845- 

ethyl  nitrite,  in  asthmatic  cases,  260. 

eucalyptus,  an  active  stimulant  expectorant,  584. 

formaldehyde,  inhalations  of,  860. 

garlic,  737. 

grindelia,  relaxes  spasm  of  bronchial  muscles  and  stimulates  mucous  mem- 
branes, 736. 

naphthalin,  when  free  expectoration,  850. 

oil  of  sandal-wood,  a  useful  stimulant  expectorant,  708,  738. 

oil  of  turpentine,  709. 

opium,  to  quiet  cough  when  not  too  free  expectoration,  134. 

physostigma,  when  there  is  weakness  of  bronchial  muscles,  237. 


894  INDEX   OF   DISEASES. 

Bronchitis,  Chronic — Continued: 

respiratory  stimulants,  often  of  great  service  in  aged  or  feeble  patients,  277. 

sanguinaria,  no  use,  739. 

senega,  of  little  value,  739. 

squill,  737. 

strychnine,  as  a  stimulant  in  the  feeble  to  aid  expulsion  of  secretion,  221, 

sulphuretted  hydrogen,  an  unpleasant  but    active    remedy   especially   where 

purulent  expectoration,  740. 

tar,  a  useful  remedy  best  employed  in  form  of  syrup.  737. 
terebene,  an  active  stimulating  expectorant,  738. 
terpin  hydrate,  a  very  useful  drug  in  cases  of  mild  type,  738. 
theocol,  847. 

Bronchorrhoea : 

expectorants,  732. 

gallic  acid,  an  internal  astringent,  406. 

Bruises : 

arnica,  373. 

camphor,  288. 

ichthyol,  528. 

solution  of  lead  subacetate,  sedative  and  astringent  embrocation,  422. 

vinegar,  a  useful  external  application,  397. 

Buboes : 

chloral,  in  solution  forms  a  stimulant  and  antiseptic  wash,  152. 
phenol,  deep  injections  of,  838. 

Bubonic  Plague: 

serum  treatment,  useful  as  prophylactic  as  well  as  curative,  550 
Burns : 

boric  acid,  as  a  mildly  antiseptic  dressing,  869. 

Carron  oil,  a  soothing  local  application,  802. 

chalk,  offers  a  desiccant  protective  dusting  powder,  803. 

creosote,  recommended  when  there  is  excessive  granulation,  844. 

hot  baths,  to  combat  the  collapse,  718. 

ichthyol,  528. 

iodoform,  analgesic,  desiccant,  and  antiseptic,  511. 

Kentish  ointment,  stimulating,  used  but  rarely,  774. 

lead  carbonate,  in  the  form  of  ointment  is  a  sedative  astringent,  use  with  care, 

422 

phenol,  anesthetic  and  germicidal,  837. 

resin  cerate,  to  stimulate  healing  process  in  old  burns,  708. 
treatment  of,  (note)   511. 
turpentine  liniment,  as  a  stimulant  to  old  ulcers,  774. 

Bursze,  Inflamed : 

phenol,  deeply  injected,  838. 

C 
Cachexia  : 

cod-liver  oil,  appears  to  have  specific  influence  on  nutrition,  517. 
glycerin,  791. 

Calculi : 

anesthetics,  to  alleviate  pain  and  produce  relaxation  during  passage  of  stone, 

82. 

atr opine,  to  relieve  spasm,  180, 

benzoic  acid,  in  uric  acid  calculi,  supposed  to  check  elimination  of  uric  acid.  863. 
piperazine,  will  not  dissolve  calculi,  698 
potassium  acetate,  to  check  the  further  deposition  of  uric  acid,  693. 

Cancer : 

arsenic,  as  a  caustic  in  inoperable  cases,  778. 
chloral,  locally  anaesthetic  and  antiseptic,  152. 
cocaine,  to  relieve  pain,  apply  locally,  207. 
escharotics,  only  to  be  used  in  inoperable  cases,  776. 


INDEX   OF   DISEASES.  895 

formaldehyde,  deodorant  and  germicidal,  860. 
iodoform,  lessens  pain  and  absorbs  discharge,  511. 
solution  of  mercuric  nitrate,  as  a  caustic,  779. 
streptococcus  toxin,  generally  fails  but  may  be  tried,  545. 

Cancer  of  Stomach  : 

bismuth  subnitrate,  to  relieve  pain  and  vomiting,  424. 
chloretone,  local  anaesthetic,  162. 

diastase,  to  digest  food  when  gastric  secretions  fail,  817. 
malt,  817. 

Carbolic  Acid  Poisoning : 

treatment,  840. 
Carbuncle : 

menthol,  paint  saturated  alcoholic  solution  over  surface,  852. 
Cardiac  Disease,  Chronic : 

See  HEART  DISEASE. 
Cardiac  Dropsy : 

See  DROPSY. 
Cardialgia : 

antacids,  correct  hyperacidity,  797. 

charcoal,  to  absorb  gases,  819. 

Cataract : 

phosphorus,  461. 

Catarrh  of  Air  Passages : 

balsam  of  Peru,  in  chronic  cases,  736. 

benzole  acid,  to  be  given  internally  in  subacute  and  chronic  cases,  863. 

camphoric  acid,  applied  locally,  288. 

compound  tincture  of  benzoin,  may  be  given  by  mouth  or  put  into  hot  water 

and  vapors  inhaled,  863. 

ftaxseed,  may  be  used  freely  in  the  form  of  a  decoction,  784. 
guaiacol,  as  a  stimulant  in  chronic  cases,  846. 
horehound,  feeble,  739. 
hydrastin,  applied  locally,  760. 
thymol  iodide,  dusted  on  the  mucous  membranes,  515. 

Catarrh  of  Bladder: 

See  CYSTITIS. 
Catarrh,  Suffocative  : 

apomorphine,  useful  in  emetic  doses  to  get  rid  of  bronchial  exudation,  642. 

expectorants,  634. 

garlic,  applied  in  the  form  of  a  poultice,  737. 

Catarrhal  Jaundice : 

See  JAUNDICE. 
Cerebral  Congestion : 

cathartics,  653. 
ergot,  753. 

Cerebral   Excitement: 

cathartics,  act  by  revulsion,  653. 

potassium  bromide,  useful  when  condition  is  not  inflammatory,  245. 

Cerebral  Scleroses: 

gold  and  sodium  chloride,  498. 

Cerebral  Softening: 

See  BRAIN  SOFTENING. 
Chancres  and  Chancroids : 

black  wash,  as  a  local  application,  496. 
Canquoin's  paste,  contains  zinc  chloride,  779. 


896  INDEX   OF   DISEASES. 

Chancres  and  Chancroids — Continued: 

corrosive  sublimate,  less  useful  than  solution  of  mercuric  nitrate  but  actively 

germicidal  and  somewhat  caustic,  779. 
eschar  otics,  776. 

hydrogen  dioxide,  cleansing  and  germicidal,  829. 
ichthargan,  actively  germicidal,  440. 
nitric  acid,  should  be  applied  with  a  glass  rod,  454,  778. 
red  mercuric  oxide,  may  be  used  in  powder  form,  496. 
resorcin,  apply  as  dusting  powder,  855. 
solution  of  mercuric  nitrate,  actively  caustic,  780. 
sulphuric  acid,  actively  caustic,  453. 
yellow  mercuric  oxide,  496. 
yellow  wash,  496. 
zinc  chloride,  caustic  and  disinfectant,  779. 

Chapped  Hands,  Lips,  or  Nipples: 

benzoic  acid,  stimulant  and  antiseptic,  especially  useful  in  the  form    of   ben- 
zoin, 863. 
glycerin,   790. 
tannic  acid,  to  harden  tender  nipples,  404. 

Chilblains : 

copaiba,  713. 
creosote,  844. 

Child-birth : 

See  LABOR. 
Chloral  Poisoning  : 

treatment  of,  152. 
Chlorosis  : 

bone  marrow,  531. 

cacodylic  acid,  doubtful  if  it  is  of  value,  482. 

cetrarin,  785. 

copper  sulphate,  an  old  remedy,  recently  revived  in  cases  with  amenorrhcea, 

428. 
iron,  the  general  facts  as  to  the  value  and  use  of  iron  in  anemia   are  discussed 

on  p.  447  and  the  individual  preparations  on  the  four  following  pages. 
lecithin,  probably  of  some  value  but  less  beneficial  than  iron,  552. 

Cholelithiasis : 

See  BILIARY  CALCULI. 
Cholera  Asiatica : 

acetozone,  an  active  intestinal  antiseptic,  830. 

ammonia,  for  the  collapse,  281. 

antitoxin,  especially  for  immunization,  550. 

camphor,  to  lessen  the  diarrhoea,  287. 

chloral,  152. 

sulphuric  acid,  of  value  as  a  prophylactic,  453. 

Cholera  Infantum : 

antipyrine,  607. 

bismuth  subnitrate,  one  of  the  most  useful  remedies  known,  424. 

Castillon's  powder,  a  means  of  exhibiting  lime,  803. 

cold  bath,  frequently  of  value,  37. 

creosote,  of  service  on  account  of  local  anesthetic  as  well  as  antiseptic  action, 

844- 

resorcin,  antiseptic,  855. 
rhubarb,  purgative  and  astringent,  663. 

sodium  phosphate,  useful  to  clean  out  bowel  and  encourage  flow  of  bile,  669. 
sulphuric  acid,  actively  astringent,  453. 

Chordee : 

camphor,  288. 
sulphonal,  157. 


INDEX   OF   DISEASES.  897 

Chorea : 

antipyrine,  has  some  effect  as  motor  sedative,  607. 

apomorphine,  has  been  recommended  in  acute  cases,  642. 

arsenic,  one  of  the  most  generally  useful  remedies,  give  Fowler's  solution  in 

increasing  doses,  474. 

cacodylic  acid,  an  arsenical  preparation,  482. 
Calabar  bean,  236. 

chloral,  to  temporarily  control  convulsions  when  violent,  151. 
cimicifuga,  give  in  conjunction  with  iron,  78. 
conium,  272. 

euquinine,  used  like  quinine,  579. 
exalgine,  617. 
quinine,  efficacious  when  patient  can  take  large  enough  quantities,  stimulates 

spinal  inhibitory  center,  572. 
sodium  bromide,  248. 

strychnine,  if  any  value  it  is  as  general  tonic,  220. 
sulphonal,  157. 
zinc  oxide,  427. 

Choroldltis  : 

santonin,  809. 
Chronic  Intestinal  Atony  : 

Calabar  bean,  a  stimulant  to  non-striated  muscle  fibre,  230. 
Chyluria : 

methylene-blue ,  581. 
Cicatrices  : 

thiosinamine,  claimed  to  have  the  power  of  absorbing  scar  tissue,  530. 

Cirrhosis  of  the  Liver: 

apocynum,  to  evacuate  effusion,  334. 

nitro-hydrochloric  acid,  in  early  stages  exercises  a  directly  beneficial  action  on 
liver,   456. 

Cocaine-poisoning : 

treatment  of,  208. 
Cocainism  : 

treatment  of,  209. 
Cold,  a  General : 

alcohol,  as  a  preventive,  304. 

Brown  mixture,  784. 

diaphoretics,  most  efficacious  treatment,  719. 

See  also  BRONCHITIS  and  CORYZA 

Colic : 

antacids,  in  conditions  with  hyperacidity,  797. 

asafetida,  in  flatulent  colic,  a  useful  stimulant  to  peristalsis,  76. 

belladonna,  useful  in  spasmodic  colic,  180. 

cajuput,  629 

chloroform,  anodyne  and  carminative,  frequently  very  useful,  99. 

ether,  mildly  carminative,  91. 

ginger,  actively  carminative,  useful  in  flatulent  colic,  628. 

opium,  to  allay  irritation,  134. 

Colica  Pictonum  : 

alum,  chemical  antidote  to  lead,  also  claimed  to  act  specifically,  410. 
belladonna,  probably  most  useful  drug  in  this  condition,  180. 
chloroform,  99. 
See  also  LEAD-POISONING. 

Colitis: 

castor  oil,  purgative  and  sedative  to  inflamed  mucous  membrane,  660. 
copper  sulphate,  occasionally  useful,  applied  locally,  428. 

forced  enemata,  best  treatment;  various  drugs,  as  silver  nitrate  or  potassium 
chlorate,  may  be  thus  locally  applied,  650 

57 


898  INDEX   OF   DISEASES. 

Colitis—  Continued  : 

magnesium  sulphate,  benefits  by  cleaning  out  the  cause,  668. 

silver  nitrate,  probably  the  most  generally  useful  local  application,  436. 

Collapse : 

ammonia,  prompt  but  temporary  stimulant,  give  hypodermically,  281. 

atropine,  of  great  service  in  the  collapse  of  low  fevers,  181. 

caffeine,  sodium  and  caffeine  benzoate  for  hypodermic  use,  348. 

counter-irritants,  768. 

digitalis,  powerfxil  but  slow,  may  be  given  hypodermically,  326. 

ergot,  slow  in  its  effect,  753. 

heat,  30. 

hot  baths,  only  efficient  method  of  maintaining  body  temperature,  718. 

sodium  carbonate,  798. 

strychnine,  one  of  the  most  generally  useful  remedies,  222. 

suprarenal  extract,  very  quick  but  fugacious,  may  be  given  intravenously,  but  a 

dangerous  remedy,  542. 
Warburg's  tincture,  579. 

Colliquative  Sweats: 

See  NIGHT-SWEATS. 
Coma : 

emetics,  633. 
Comedo : 

arsenic,  474. 
Condylomata : 

chromic  acid,  caustic,  780. 

nitric  acid,  actively  caustic,  780. 

phenol,  mildly  caustic,  837. 

Congestion  of  Brain : 

See  CEREBRAL  CONGESTION. 
Congestion  of  Lungs : 

atr opine,  181. 
ergot,  753. 

Congestion  of  Spinal  Cord: 

ergot,  753. 
Conium -poisoning : 

treatment  of,   273. 
Conjunctivitis : 

alum,  in  the  form  of  alum   curd,  astringent,  410. 

atropine,  rests  the  eye  and  has  an  anodyne  alterative  effect,  181. 

betanaphtol,  applied  locally  dissolved  in  olive  oil,  851. 

boric  acid,  one  of  the  best  local  applications,  soothing  and  antiseptic,  869. 

citrine  ointment,  in  chronic  cases,  496. 

cocaine,  lessens  pain  and  overcomes  congestion,  a  very  useful  treatment,  207. 

copper  sulphate,  used  in  the  granular  type,  429. 

ichthargan,  may  be  topically  applied  in  one  per  cent,  solution,  440. 

largin,  a  modern  silver  preparation  recommended  in  the  form  of  gelatin 
tablets  locally,  439. 

lithium,  in  gouty  cases,  698 

protargol,  recommended  especially  in  gonorrhceal  cases,  441. 

silver  nitrate,  a  standard  and  useful  treatment,  an  active  germicide  and  astrin- 
gent, 435. 

suprarenal  extract,  powerfully  antagonizes  the  congestion,  542. 

yellow  mercuric  oxide,  in  chronic  cases,  496. 

Constipation : 

aloes,  in  atonic  cases,  especially  when  accompanied  with  amenorrhrea,  665. 
asafetida,  as  stimulant  to  the  intestinal  muscles,  especially  useful  in  the  aged, 
76. 


INDEX   OF   DISEASES.  899 

belladonna,  prevents  griping  and  increases  laxative  effects  of  cathartics,  180. 

black  draught,  a  very  valuable  remedy  in  fecal  impaction,  666. 

blue  mass,  used  where  hepatic  torpor,  662. 

bran,  654. 

calomel,  most  valuable  drug  in  biliousness,  not  to  be  used  habitually,  662. 

cascara  sagrada,  especially  useful  in  chronic  constipation,  655. 

castor  oil,  useful  only  in  acute  cases,  659. 

cathartics,  652. 

compound  cathartic  pills,  in  acute  constipation,  672. 

compound  infusion  of  senna,  same  as  black  draught,  666. 

cracked  wheat,  654. 

croton  oil,  probably  most  powerful  purgative  known  used  to  revulse  or  when 
patients  refuse  to  swallow,  675. 

diet,  654. 

enemata,  650. 

Epsom  salt,  a  prompt  and  efficient  saline,  667. 

euonymus,  655. 

Indian  meal,  654. 

magnesia,  antacid  laxative,  657. 

manna,  655. 

molasses,  654. 

oatmeal,   654. 

physostigma,  stimulant  to  intestinal  muscles,  useful  in  atonic  cases,  273. 

pills  of  aloes  and  asafctida,  666. 

podophyllum,  supposed  to  act  upon  the  liver,  hence  the  name  "vegetable  mer- 
cury," 673. 

rhttbarb,  used  in  debilitated  cases,  663. 

Seidlitz  powder,  an  elegant  form  of  saline,  669. 

senna,  a  very  efficient  laxative  when  soft  passages  desired,  666. 

solution  of  magnesium  citrate,  non-irritating,  especially  useful  in  inflamma- 
tory conditions,  668. 

strychnine,  when  intestinal  atony,  222. 

sugar,  654. 

sulphur,  657. 

tamarind,  656. 

taraxacum,  504. 

treatment  of,  652. 

unbolted  flour,  654. 

vegetable  cathartic  pills,  670. 

wahoo,  in  chronic  cases  with  hepatic  torpor,  655. 

Convulsions : 

amyl  nitrite,  the  remedy  when  convulsions  must  be  controlled  immediately, 

quick  and  powerful  but  fugacious,  258. 

anesthetics,  when  prompt  action  desired;  chloroform  the  most  efficacious,  82. 
asafetida,  in  hysterical  cases,  76. 
camphor,  of  little  value  except  in  hysteria,  288. 
chloral,  useful  in  all  types  of  convulsions  if  severe  enough  to  threaten  life, 

IS1.  !S2- 

emetics,  when  convulsions  of  gastric  origin,  633. 
garlic,  737. 
musk,  74. 

potassium  bromide,  a  useful  remedy  when  a  persistent  action  desired,  246. 
See  also  EPILEPSY,  TETANUS,  etc. 

Copper-poisoning : 

treatment  of,  430. 
veratrum  viride,  345. 

Corneal   Ulcer : 

atr -opine,  rests  the  eye  by  paralyzing  accommodation,  183. 
dionine,  increases  the  lymphatic  circulation  in  the  eye,  144. 
largin,  germicidal,  439. 
physostigmine,  to  limit  the  spread  of  ulcers,  237. 

Corpulence : 

See  OBESITY. 


900  INDEX   OF   DISEASES. 

Cory za : 

air? pine,  give  internally  in  acute  stage;  it  checks  excessive  secretion,  181. 

oismuth  subnitrate,  locally  applied,  soothing  and  protective,  425. 

cocaine,  contracts  the  engorged  vessels.  206. 

cubebs,  as  a  snuff  in  not  too  acute  conditions,  714. 

glycerin,  locally,  791. 

ichthyol,  a  ten  per  cent,  ointment  locally,  528. 

salipyrin,  615. 

validol,  apply  locally,  75. 

Cough  : 

air  opine,  when  cough  is  of  spasmodic  character,  180. 

codeine,  acts  on  respiratory  center,  142. 

dionine,    1 43 . 

gelsemium,   267. 

heroine,  one  of  most  generally  useful  cough  sedatives  known,  145. 

opium,  to  be  avoided  when  expectoration  is  profuse,  134. 

prussic  acid,  of  little  value,  391. 

treatment  of,   730. 

Croup : 

compound  syrup  of  squill,  not  suitable  for  children,  737. 

emetics,  to  evacuate  membrane  or  mucus,  634. 

expectorants,  731. 

glycerin,  791. 

ipecacuanha,  emetic  and  expectorant,  637. 

lime-water,  apply  locally  by  means  of  an  atomizer,  803. 

squill,  nauseating  expectorant,  737. 

sulphonal,  157. 

yellow  mercuric  subsulphate,  a  dangerous  remedy,  496. 

Cystitis : 

arbutin,  alterative  diuretic,  706. 

benzoic  acid,  valuable  urinary  antiseptic,  especially  useful  when  ammoniacal 
urine,  863. 

betol,  antiseptic,  852. 

boric  acid,  antiseptic,  may  be  given  by  mouth  or  used  to  wash  out  bladder,  868. 

buchu,  acts  as  sedative  to  inflamed  mucous  membrane,  705. 

camphoric  acid,  288. 

cantharides,  stimulating,  use  only  in  chronic  cases,  715. 

copaiba,  in  chronic  cases,  713. 

flaxseed,  infusion,  sedative  to  mucous  membrane,  useful  in  acute  cases,  784. 

grindelia,   736. 

guaiacol,  urinary  antiseptic,  846. 

helmitol,  supposed  to  liberate  formaldehyde,  701. 

hexamethylenamine,  one  of  the  best  urinary  disinfectants,  supposed  to  lib- 
erate formaldehyde  in  the  bladder,  699. 

hippurate  of  lime  andlithia,  (note)  86 1. 

iodine,  504. 

juniper,  in  chronic  cases,  707. 

lycetol,  especially  in  lithemic  patients,  699. 

methylene-blue,  mildly  antiseptic,  581. 

pareira,  705. 

resorcin,  a  three  per  cent  solution  employed  to  irrigate  the  bladder,  855. 

salicylic  acid,  rarely  used  to-day,  594. 

silver  citrate,  as  local  application  to  bladder,  438. 

terebene,  stimulant  alterative  diuretic,  738. 

terpin  hydrate,  738. 

triticum,  sedative  to  cystic  mucous  membrane,  706. 

turpentine,  in  chronic  cases,  712. 

urasol,  supposed  to  act  as  antiseptic,  702. 

urotropin,  proprietary  preparation  of  hexamethylenamine,  699. 

uva  nrsi,  a  valuable  sedative  alterative  diuretic,  705. 


INDEX   OF    DISEASES.  901 

D 
Debility  . 

See  NEURASTHENIA. 

Delirium  of  Low  Fevers: 

blisters,  when  condition  is  not  due  to  exhaustion,  768. 
chloral,  in  early  stages,  1 50. 
valerian,  75. 

Delirium  Tremens  : 

chloral,  to  produce  sleep,  powerful  but  depressant,  i  50. 

chloretone,  164. 

digitalis,  to  maintain  circulation,  large  doses  well  borne,  327. 

hops,  77. 

hyoscine   hydrobromide,    a   useful   hypnotic,    especially   in   combination  with 

morphine,  189. 

monobromated  camphor,  of  little  value,  79,  251. 
opium,  serviceable,  but  not  to  be  used  too  lavishly,  133. 
paraldehyde,  a  useful  somnifacient,  161. 

potassium  bromide,  as  a  general  nerve  sedative,  not  to  produce  sleep,  245. 
valerian,  too  feeble,  75. 
veratrum,  capable  of  harm,  369. 

Dermal  Growths  : 

chromic  acid,  caustic,  780. 
nitric  acid,  caustic,  780. 

Dermatitis  : 

vinegar,  a  soothing  astringent  lotion,  397. 

Diabetes  Insipidus  : 

antipyrine,  609. 

ergot,  probably  the  most  generally  useful  remedy  known,  753. 

exalgine,  617. 

oil  of  turpentine,  711. 

opium,  may  be  used  in  combination  with  gallic  acid,  134. 

Diabetes  Mellitus  : 

antipyrine,  609. 

arsenical  solution  of  lithium,  in  gouty  cases,  (note)  698. 

ergot,  may  do  good,  usually  fails.  753 

eucalyptus,  584. 

glycerin,  as  a  sweetening  agent  instead  of  sugar,  791. 

hydrogen  dioxide,  probably  of  no  service,  829. 

jambul,  in  some  cases  may  greatly  reduce  sugar,  usually  no  effect,  529. 

lecithin,  recommended  to  improve  nutrition,  552 

opium,  the  most  valuable  drug  in  this  condition,  use  in  large  doses,  134. 

piperazine,  recommended  on  scientific  grounds,  (note)  699. 

saccharin,  extraordinarily  sweet,  used  as  substitute  for  sugar,  792. 

sodium  carbonate,  800. 

thymol,  851,  853 

Diarrhoea : 

antacids,  in  cases  with  "spinach-stools",  795. 

antipyrine,  609. 

argentol,  as  an  astringent  antiseptic,  438. 

aromatics,  in  diarrhoeas  of  relaxation,  626. 

astringents,  402. 

att -opine,  in  colliquative  diarrhoeas,  181. 

bismuth  and  ammonium  citrate,  differs  essentially  from  other  salts  of  bismuth, 

useful  only  in  serous  types,  426. 
bismuth  subgallate,  426. 
bismuth  subnitrate,  perhaps  the  most  generally  useful  remedy  we    have    in 

diarrhoeas  of  an  inflammatory  character,  acts  as  a  sedative,  protective 

antiseptic  and  astringent,  424 


902  INDEX   OF   DISEASES. 

Diarrhoea —  Continued  : 

bismuth  subsalicylate ,  acts  about  like  the  subnitrate,  426. 

calcium  carbonate,  in  summer  diarrhoeas  when  intestines  are  acid,  803. 

calcium  chloride,  asserted  to  inhibit  peristalsis,  suggested  in  nervous  types,  804. 

camphor,  in  serous  forms  of  diarrhoea,  287. 

Castillon's  powder,  803. 

castor  oil,  useful  to  cleanse  bowel  in  inflammatory  diarrhoea,  is  sedative,  660. 

cocaine,  207. 

cold  baths,  in  summer  diarrhoeas  often  very  useful,  37. 

copaiba,  in  chronic  cases,  713. 

copper  sulphate,  used  in  chronic  ulcerative  types,  but  is  of  little  value,  429. 

creosote,  intestinal  antiseptic,  844. 

cresol,  antiseptic,  849. 

ergot,  in  chronic  serous  diarrhoeas  restores  tone  to  relaxed  vessels,  a  valuable 

remedy,  752. 

ferrous  sulphate,  astringent,   employed  in  chronic  cases,  449. 
gambir,  a  powerful  astringent  in  relaxing  diarrhoeas,  407. 
geranium,  contains  tannin,  especially  used  in  children,  409. 
hcematoxylon,  efficient  astringent  with  pleasant  taste,  408. 
hamamelis,  408. 

Hope's  camphor  mixture,  a  valuable  combination  in  serous  diarrhoeas,  455. 
ipecacuanha,  in  chronic  cases,  639. 
jambul,  529. 

kino,  actively  astringent,  529. 

lead  acetate,  employed  in  serous  diarrhoeas  combined  with  opium,  422. 
lime-waler,  especially  when  acidity  of  intestines,  802. 
magnesia,  in  cases  with  intestinal  acidity,  656. 
naphtol,  a  valuable  intestinal  antiseptic,  85. 
nitric  acid,  454. 

nitro-hydrochloric  acid,  in  chronic  cases  with  hepatic  torpor,  456. 
nitrous  acid,  preferred  in  Hope's  camphor  mixture  to  nitric  acid,  455. 
oil  of  cajaput,  629. 
opium,  lessens  both  peristalsis  and  secretion,  to  be  used  in  serous,  not  in 

mucous,  diarrhoeas,  134. 
pepsin,  8 1 6. 

phenol,  as  an  intestinal  antiseptic,  837. 
rhatany,  408. 

rhubarb,  cathartic  and  astringent;  of  service  in  summer  complaint,  663. 
sodium  phosphate,  useful  in  chronic  diarrhoea  of  infants,  669. 
strychnine,  in  atonic  cases,  222. 
sulphuric  acid,  an  active  astringent,  453. 
syrup  of  lime,  806. 
tannalbin,  possesses  the  astringent  properties  of  tannin  without  deleterious 

effects  upon  the  stomach,  405. 

tannic  acid,  in  serous  types  to  check  excessive  secretion,  404. 
tannoform,  claimed  to  combine  antiseptic  influence  of  formaldehyde  to  as- 

tringency  of  tannin,  405. 
tannopine,  405. 

zinc  oxide,  in  chronic  catarrhal  varieties,  427. 
zinc  sulphate,  in  chronic  diarrhoea  with  ulcerations,  427. 

Digitalis-poisoning : 

treatment  of,  330. 

Dilatation  of  Heart : 

convallaria,  350. 
digitalis,  323. 

Dilatation  of  Stomach : 

beta-naphtol,  to  check  fermentation,  851. 

Diphtheria : 

antitoxin,  specific,  use  early  and  freely,  545. 

benzoic  acid,  locally  as  antiseptic,  863. 

boric  acid,  869. 

cold,  ice  bag  over  the  throat,  31;  to  reduce  fever,  37. 


INDEX   OF   DISEASES.  903 

colloidal  silver,  used  by  inunction,  of  doubtful  value,  439. 

creosote,  apply  locally  as  antiseptic,  844. 

hydrochloric  acid,  to  destroy  membrane,  454. 

hydrogen  dioxide,  one  of  the  most  useful  germicides,  apply  with  swab,  829. 

faborandi,  726. 

lime-water,  to  dissolve  the  membrane,  803. 

mercury,  after  antitoxin  probably  the  most  valuable  internal  remedy;  calomel 
may  be  dusted  on  diseased  surface,  489. 

Monsel's  solution,  apply  locally,  astringent,  449. 

papain,  to  dissolve  membrane,  818. 

phenol,  germicidal,  may  be  used  in  form  of  lozenge,  837. 

potassium  chlorate,  dangerous  internally  on  account  of  irritant  effect  on  kid- 
neys, may  be  applied  locally,  697. 

resorcin,  antiseptic  and  feebly  caustic,  855. 

salicylic  acid,  of  no  value,  594. 

streptococcus  antitoxin,  may  be  used  for  mixed  infections,  548. 

tincture  of  ferric  chloride,  value  doubtful,  450. 

Dislocation : 

anesthetics,  82. 

Diuresis,  Excessive : 

turpentine,  711. 

Dropsy  : 

apocynum,  diuretic  and  cardiac  stimulant,  334. 

blisters,  in  local  dropsies,  768. 

caffeine,  actively  diuretic,  348. 

calomel,  a  powerful  diuretic  if  used  in  large  doses,  683. 

cathartics,  653. 

convallaria,  is  diuretic  and  sometimes  cathartic,  350. 

copaiba,  713. 

diaphoretics,  719. 

digitalis,  increases  urinary  secretion  by  stimulating  the  circulation,  320,  686. 

diuretics,  668. 

elaterin,  hydragogue  cathartic,  especially  useful  in  renal  dropsies,  674. 

hot  baths,  718. 

jaborandi,  eliminates  the  fluid  through  the  skin,  726. 

jalap,  hydragogue  cathartic,  use  in  the  form  of  compound  jalap  powder,  671. 

magnesium  sulphate,  eliminates  fluid  through  the  bowels,  668. 

potassium  bitartrate,  non-irritant  diuretic,  693. 

scoparius,  diuretic  but  irritant  to  kidneys,  682. 

squill,  powerful  diuretic,  avoid  in  acute  Bright's  disease,  681. 

strophanthus,  cardiac  stimulant,  has  more  action  on  kidneys  than  digitalis, 

337- 

sugar,    687. 

theobromine,  useful  in  either  cardiac  or  nephritic  dropsy,  685. 
theocin,  diuretic,  685. 
veratrine,  372. 

Dysentery : 

calomel,  internally  in  fractional  doses  every  hour,  antiphlogistic  and  purgative, 
662. 

castor  oil,  purgative,  also  soothing  to  inflamed  mucous  membrane,  660. 

cathartics,  653. 

cocaine,  in  the  form  of  suppositories  when  irritability  of  rectum,  207. 

cold,  ice  suppositories  or  injections  of  ice-water  of  great  value,  38. 

copaiba,  in  chronic  cases,  713. 

creosote,  844. 

enemata,  a  very  important  part  of  the  treatment  of  dysentery  is  the  applica- 
tion of  various  drugs  to  the  inflamed  area  by  means  of  the  high  enema, 
650. 

ergot,  useful  in  chronic  cases,  752. 

flaxseed,  to  be  used  freely  in  form  of  decoction,  784. 

forced  enemata,  650. 

glycerin,  applied  locally  by  means  of  enema,  791. 


904  INDEX   OF   DISEASES. 

Dysentery —  Continued  : 
iodine,  504. 

iodoform,  in  the  form  of  suppositories  as  local  anodyne,  513. 
ipecacuanha,  except  the  purgatives  ipecac  in  large  doses  the  most  valuable 

drug  which  can  be  given  by  mouth,  638. 
naphtol,  851. 

nitrous  acid,  in  chronic  dysentery  of  hot  climates,  455. 
opium,  acts  as  antiphlogistic  and  analgesic  (134),  may  be  given  by  rectum 

(140). 

potassium  chlorate,  useful  for  rectal  injections  in  chronic  cases,  697. 
potassium  permanganate,  wash  out  colon  with  one  to  two  thousand  solution, 

827. 

silver  nitrate,  by  rectal  injection  in  chronic  cases,  435. 
sulphur,  seems  to  act  as  intestinal  antiseptic,  highly  recommended,  658. 

Dysmenorrhoea : 

amyl  nitrite,  in  spasmodic  type,  259. 

antipyrine,  to  relieve  pain,  608. 

air  opine,  in  spasmodic  type,  180. 

black  haw,  744. 

camphor,  in  nervous  cases,  287. 

cotton-root,  has  stimulant  action  of  the  uterus,  764. 

guaiac,  stimulant  to  uterine  mucous  membrane,  742. 

nydrastinine  hydrochlorate,  stimulant  to  uterus,  763. 

thermal,  to  relieve  pain,  618. 

viburnum,  744. 

Dyspepsia : 

alcohol,  often  relieves,  but  danger  of  habit,  307. 

antacids,  curative  as  well  as  alleviating,  797. 

asafetida,  in  atonic  cases,  76. 

barberry,  623. 

calcium  chloride,  recommended  in  fermentative  cases,  803. 

charcoal,  as  an  absorbent  in  fermentative  dyspepsia,  819. 

enemata,  650. 

euonymus,  as  a  laxative,  656. 

finger,  must  not  be  used  when  there  is  inflammation,  628. 
ydrastis,  760. 

hydrochloric  acid,  as  a  digestant  where  insufficient  gastric  secretion,  454. 
magnesia,  of  value  in  acid  dyspepsia,  656. 
naphtol,  antiseptic,  useful  where  much  fermentation,  851. 
nitric  acid,  to  replace  the  hydrochloric  acid  of  stomach,  455. 
pancreatin,  cannot  have  any  effect  as  digestant,  816. 
pepper,  may  be  used  in  atonic  types,  628. 

pepsin,  used  where  gastric  secretion  fails,  usually  of  little  benefit,  816. 
physostigma,  in  intestinal  dyspepsia,  237. 

silver  nitrate,  valuable  astringent  in  true  gastritis,  especially  when  ulcer  pres- 
ent, 436. 

soda,  corrects  hyperacidity,  encourages  gastric  secretion,  800. 
strychnine,  when  associated  with  atony,  222. 
taraxacum,  530. 
terebenc,  in  flatulent  intestinal  dyspepsia,  738. 

Dyspnoea : 

aspidosperma,  active  respiratory  stimulant,  278. 
oxycamphor,  respiratory  sedative  and  cardiac  stimulant,  291. 
physostigma,  when  dependent  on  bronchitis,  236. 


Eclampsia : 

See  also  PUERPERAL  CONVULSIONS. 
Eczema : 

ancesthesin,  to  relieve  itching,  used  as  ointment,  118. 
arsenic,  internally,  beneficial  in  chronic  cases,  473. 
betanaphtol,  oily  solution,  locally  applied,  851. 


INDEX   OF   DISEASES.  905 

bismuth  subgallate,  as  a  dusting  powder,  426. 

cacodylic  acid,  an  arsenical  preparation,  482. 

camphor-menthol,  (note)  852. 

glycerin,  useful  emollient,  790. 

ichlhargan,  440. 

ichthyol,  a  very  useful  external  application,  527. 

menthol,  to  relieve  itching,  852. 

papain,  to  destroy  thickened  skin,  818. 

resorcin,  a  valuable  local  application  in  chronic  cases,  855. 

soft  soap,  765. 

suprarenal  capsule,  to  blanch  reddened  areas  in  chronic  cases,  542. 

tannoform,  406. 

zinc  oxide  ointment,  a  useful  astringent  application,  428. 

Effusion,  Pericardia! : 

potassium  iodide,  aids  the  absorption  of  fluids,  506. 
squill,  eliminates  fluid  through  kidneys,  68 1. 

Effusion,  Pleura! : 

antipyrine,  609. 

iodoform,  as  a  substitute  for  iodides,  510. 

potassium  iodide,  506. 

squill,  68 1. 

sugar,  diuretic,  687. 

Emesis : 

See  VOMITING. 
Emphysema : 

aspidosperma,  278. 
Empy ema  : 

creosote,  locally  as  disinfectant,  844. 

iodine,  inject  after  cleaning  out  cavity,  504. 

iodoform,  in  tuberculous  cases  glycerin  solution  locally  applied,  513. 

Endocarditis : 

aconite,  when  cardiac  excitement  or  excessive  hypertrophy,  382. 

camphor,  as  a  stimulant  where  immediate  danger  of  heart  failure,  287. 

convallaria,  much  disagreement  as  to  its  value,  350. 

digitalis,  the  most  reliable  stimulant  and  heart  tonic  in  all  cases  where  com- 
pensation is  lost,  323,  326. 

ichthargan,  has  been  injected  intravenously  in  septic  cases,  doubtful  if  it 
be  a  method  of  value,  440. 

mercury,  489. 

sparteine,  occasionally  of  service  as  heart  stimulant,  353. 

suprarenal  extract,  value  very  doubtful,  543. 

See  also  HEART  DISEASE. 

Endometritis : 

hydrastininc  hydrochlorate ,  763. 
thyroid  extract,  537. 

Enteric  Fever: 

See  TYPHOID  FEVER. 
Enteritis : 

ammonium  chloride,  734. 

bismuth,  the  insoluble  salts  of  bismuth  (subnitrate,  subcarbonate,  subgallate, 

subsalicylate)  are  our  most  efficient  remedies  in  enteritis,  424. 
castor  oil,  useful  to  cleanse  the  bowel,  also  sedative  to  inflamed  mucosa,  660. 
cathartics,  benefit  by  getting  rid  of  irritating  substance,  use  in  beginning  of 

treatment,  653. 

chlorine,  recommended  as  an  intestinal  antiseptic,  820. 
copper  sulphate,  428. 

demulcents,  soothe  the  inflammation,  use  in  acute  cases,  782. 
enemata,  650. 


906  INDEX   OF    DISEASES. 

Enteritis —  Continued : 

flaxsced,  used  as  demulcent  in  the  form  of  a  decoction,  784. 

hydrastis,  beneficial  especially  in  chronic  cases,  760 

magnesium  sulphate,  a  non-irritating  cathartic,  668. 

naphtalin,  as  an  intestinal  disinfectant,  850. 

opium,  should  be  used  for  antiphlogistic  effects,  not  to  check  the  diarrhoea, 

134- 

physostigma,  in  chronic  cases,  237. 
resorcin,  855. 
silver  nitrate,  436. 
slippery  elm,  demulcent.  783. 
tannalbin,  a  non-irritant  astringent,  405. 
See  also  DIARRHCEA. 

Enuresis : 

See  INCONTINENCE  OP  URINE. 

Ephemeral  Fever: 

aconite,  383. 

Epidid ymitLs : 

silver  nitrate,  painted  over  the  scrotum,  435. 

Epilepsy : 

acetanilid,  612. 

ammonium  bromide,  especially  useful  in  combination  with  strontium  bromide, 

248. 

amyl  nitrite,  in  cases  with  a  distinct  aura,  or  in  status  epilepticus,  248. 
anaesthetics,  rarely  needed  except  in  status  epilepticus,  82. 
antipyrine,  efficacious  in  some  cases,  may  be  tried  in  any,  603. 
borax,  probably  of  no  value,  869. 
bromahn,  251. 

bromipin,  administered  either  hypodermically  or  by  inunction,  251. 
calcium  bromide,  less  disturbing  to  digestion  than  other  bromides,  249. 
camphor,  288. 

chloretone,  recommended  especially  in  petit  mal,  162. 
ergot,  increases  effect  of  bromides,  753. 
gold  bromide,  250. 

hydrastinine  hydrochlorate,  theoretically  is  strongly  indicated,  761,  763. 
hydrobromic  acid,  too  irritant  to  be  used  alone  but  may  be  combined  with 

alkaline  bromide,  250. 
lithium  bromide,  claimed  to  do  good  in  cases  in  which  potassium  salt  has 

failed,  249. 
physostigma,  237. 
pituitary  body,  no  good,  543. 

potassium  bromide,  the  standard  remedy  in  epilepsy,  246. 
santonin,  807. 
silver  nitrate,  useless,  436. 

sodium  bromide,  about  equivalent  to  the  potassium  bromide,  248. 
strontium  bromide,  slow  but  persistent  in  its  action,  249. 
sulphonal,  157. 

zinc  bromide,  by  some  believed  of  service,  but  doubtful  if  of  value,  428. 
zinc  oxide,  427. 

Episcleritis : 

physostigmine,  237 

Epistaxis  : 

cocaine,  acts  by  constricting  blood-vessels,  207. 

ergot,  of  little  if  any  value,  752. 

gelatin,  may  be  employed  with  advantage  both  locally  and  internally,  533. 

suprarenal  extract,  a  very  powerful  local  constrictor  of  blood-vessels,  542. 

tannic  acid,  acts  by  coagulating  blood  and  contracting  vessels,  404. 

Epithelioma : 

resorcin,  as  a  caustic,  855. 


INDEX   OF   DISEASES.  907 

Erysipelas : 

antipyrine,  to  reduce  the  temperature,  607. 

alropine,  as  a  circulatory  stimulant,  181. 

benzoic  acid,  as  an  antiseptic,  863. 

boric  acid,  saturated  solution  applied  locally,  869. 

creosote,  used  in  the  form  of  an  ointment,  844. 

ferrous  sulphate,  as  an  astringent  lotion,  449. 

ichthyol,  527. 

iodine,  beneficial  results  from  local  application  but  must  not  be  used  too  freely 

5°3- 

phenol,  deep  injections,  838. 

streptococcus  antitoxin,  has  not  fulfilled  expectations,  but  may  be  tried,  548. 
tincture  of  ferric  chloride,  specific  action  from  internal  use,  450. 

Excoriations  : 

glycerin,  soothing  and  softening,  790. 

Exophthalmic  Goitre: 

picric  acid,  814. 

sparteine,  to  relieve  the  cardiac  symptoms,  353. 
splenic  extract,  well  worth  trying,  544. 
strophanthus,  to  control  the  heart  action,  337. 
thymus  gland,  has  not  proved  of  service,  543. 


Fatty  Heart: 

See  HEART  DISEASE. 
Faucitis : 

See  SORE  THROAT. 
Favus : 

naphthol,  in  the  form  of  a  soap,  851. 
Fecal  Accumulation : 

black  draught,  a  very  efficient  remedy,  666. 
Epsom  salt,  668. 

linseed  oil,  by  rectal  injection,  787. 
senna,  666. 

Feet,  Sweating  of : 

See  HYPERIDROSIS. 
Feet,  Tender: 

tannic  acid,  404. 
Felon : 

carbolic  acid,  injected  deeply,  838. 

silver  nitrate,  to  abort,  paint  finger  with  solution  of,  435. 

Fever : 

acetanilid,  probably  less  depressant  than  antipyrin,  613. 

acetofyrin,  coal  tar  antipyretic,  610. 

aconite,  useful  febrifuge  in  mild  fevers,  383. 

alcohol,  acts  as  accessory  food  and  cardiac  stimulant,  305. 

ammonia,  281 

antipyretics,  less  serviceable  than  cold    bath  in  severe  fever,  586. 

antipyrine,  to  lessen  fever,  607. 

apirin,  especially  in  rheumatic  fever,  598. 

cardiac  depressants,  increase  heat  elimination,  359. 

chloral,  as  a  sedative,  1 50. 

cold,  most  rational  mode  of  reducing  temperature,  37  methods  of  applying,  39. 

diaphoretics,  useful  to  break  up  some  kinds  of  fever,  719. 

digitalis,  to  maintain  circulation,  327. 

diuretics,  water  especially  useful  in  febrile  conditions,  677. 

eupyrine,  antipyretic,  608. 


908  INDEX    OF    DISEASES. 

Fever-r-  Continued  : 
exalgine,  617. 

gelsetnium,  as  arterial  sedative  in   sthenic  fevers,  266. 
hydrogen  dioxide,  probably   no  value. 
jaborandi,  efficacious  sudorific,  726. 
lemon- juice,  as  refrigerant  drink,  396. 
neutral  mixture,  as  diaphoretic,  692. 
nitric  acid,  455. 
oil  of  turpentine,  711. 
opium,  to  support  the  system,  134. 

phenacctin,  probably  safest  of  coal-tar  antipyretics,  615. 
phcnocoll  hydrochloride,  616. 
potassium  citrate,  692. 

quinine,  useful  in  conjunction  with  cold  bath,  570. 
salicylic  acid,  not  generally  useful  as  antipyretic,  593. 
salipyrin,  as  antipyretic  especially  in  rheumatic  fever,  617. 
saloquinine,   580. 
solution  of  potassium  citrate,  692. 

sweet  spirit  of  nitre,  in  adynamic  fevers  of  children,  728. 
thermal,  coal  tar  antipyretic,  6r8. 
See  also  TYPHOID  FEVER,  SCARLET  FEVER,  etc, 

Fibroid  Tumors  of  Uterus  : 

See  UTERUS,  FIBROID  TUMORS  OF. 

Fissure  of  Anus: 

atr  opine,  to  relieve  accompanying  spasm,  180. 
benzoic  acid,  antiseptic  and  healing,  863. 
cocaine,  as  a  local  anaesthetic,  207. 

Fistula : 

creosote,  844. 

Flatulence  : 

dramatics,  to  stimulate  intestinal  peristalsis,  625. 
asafetida,  enemata  in  flatulent  constipation,  76. 
Hoffmann  s  anodyne,  carminative,  77. 
physostigma,  a  stimulant  to  intestinal  muscle,  237. 
See  also  COLIC. 

Fractures  : 

calcium  phosphate,  in  ununited  fractures,  520. 

sulphonal,  to  relieve  muscular  spasm,  157. 

thyroid  extract,  has  sometimes  proved  useful  in  delayed  union,  540. 

Frost-Bites  : 

ichthyol,  528. 

Furuncles : 

See  BOILS. 

O 
Galactorrhoea : 

antipyrine,  609. 

belladonna,  either  internally  or  applied  locally  to  breasts,  181. 

ergot,  753. 

Oall-Stones : 

See  BILIARY  CALCULI. 

Gangrene : 

carbolic  acid,  837. 
nitric  acid,  454. 

Gangrene  of  the  Lungs: 

phenol,  837. 


INDEX   OF    DISEASES.  909 

Gastralgia : 

ancesthesin,  a  local  anaesthetic,  118. 

arsenic,  in  neuralgic  types,  474. 

bismuth,  especially  in  feeble  patients,  424. 

hydrocyanic  acid,  a  useful  remedy,  probably  acts  on  sensory  nerves,  392. 

manganese  dioxide,  451. 

orthoform,  useful  in  cases  of  gastric  ulcer,  1 18. 

phenol,  of  value  on  account  of  local  anaesthetic  action  as  well  as  antiseptic,  837. 

validol,  a  compound  of  menthol  and  valeric  acid,  75. 

Gastric  Crisis: 

See  LOCOMOTOR  ATAXIA. 

Gastric  Ulcer: 

copaiba,  as  a  stimulant  in  chronic  and  indolent  ulcers,  713. 

ichthargan,  a  combination  of  silver  and  ichthyol,  440. 

orthoform,  to  lessen  pain  through  local  anaesthetic  effect,  118. 

resorcin,  a  not  generally  useful  remedy,  855. 

silver  nitrate,  the  standard  remedy,  sedative,  astringent,  and  antiseptic,  436. 

Gastric  Uneasiness: 

antacids,  797. 

Gastritis  : 

ammonium  chloride,  in  chronic  cases,  734. 

bismuth,  all  its  insoluble  salts  act  similarly;  they  are  sedative,  astringent, 

protective,  and  antiseptic,  424. 
calcium  chloride,  803. 

demulcents,  in  acute  inflammations  may  be  freely  employed,  782. 
hydrastis,  useful  especially  in  chronic  cases,  760. 
ichthargan,  442. 

phenol,  antiseptic  and  anaesthetic,  837. 
silver  nitrate,  useful  sedative  astringent,  436. 
See  also  DYSPEPSIA. 

Gingivitis : 

argyrpl,  germicidal,  441. 
tannin,  astringent,  404. 

Glands,  Enlarged : 

ammonium  iodide,  may  be  used  both  internally  and  externally,  507. 

cod-liver  oil,  to  improve  nutrition  in  scrofula,  517. 

ichthyol,  applied  externally,  528. 

iodine,  used  externally  in  indolent  hypertrophy,  504. 

iodoform,  either  by  mouth  (510)  or  glycerin  solution  injected  into  tuberculous 

glands,  513. 

mercurial  ointment,  in  enlarged  indurated  glands,  493. 
mercurial  plaster,  493. 

naphtol,  alcoholic  solution  to  be  injected  directly  into  glands,  851. 
phenol,  deeply  injected,  838. 
sulphurated  hme,  659. 
thiosinamine,  especially  in  cases  with  fibrous  tissue,  530. 

Glaucoma : 

dionine,  used  locally  increases  the  flow  of  lymph  in  the  eye,  143. 
physostigmine,  relieves  ocular  tension  by  contracting  the  pupil,  237. 
salicylic  acid,  useful  especially  in  rheumatic  cases,  594. 

Gleet : 

cantharides,  a  powerful  stimulant  to  the  urethral  mucous  membrane,  715. 
tincture  of  ferric  chloride,  in  combination  with  cantharides,   450. 
turpentine,  a  stimulant  alterative  diuretic,  712. 

Glycosuria : 

See  DIABETES  MELLITUS. 


9io  INDEX   OF   DISEASES. 

Goitre : 

iodine,  useful  in  true  goitre,  503. 

thyroid  extract,  only  in  simple  goitre,  not  in  exophthalmic,  538. 

Goitre,  Exophthalmic: 

See  EXOPHTHALMIC  GOITRE. 

Gonorrhoea : 

acetozone,  locally  as  antiseptic,  830. 

albargin,  a  silver  preparation,  438. 

antimony,  internally  as  a  circulatory  depressant  and  diaphoretic,  364. 

argonin,  a  silver  preparation,  440. 

argyrol,  claimed  to  be  a  non-irritant  and  active  silver  preparation,  439. 

benzoic  acid,  internally  as  urinary  antiseptic,  863. 

betol,  given  internally,  850. 

bismuth,  used  locally  in  later  stages,  713. 

copaiba,  in  the  beginning  stages  employed  internally,  425 

hydraslin,  locally  in  the  later  stages,   758. 

hydrogen  dioxide,  829. 

ichthargan,  active  silver  preparation,  440. 

kava,  715. 

largin,  recommended  especially  in  gonorrhoea  in  women,  439. 

matico,  714. 

methylene-blue,  of  doubtful  value,  581. 

oil  of  erigeron,  707. 

oil  of  sandal-wood,  used  internally  in  the  advanced  stages,  708. 

pareira,  in  chronic  gonorrhoea  as  alterative  diuretic,  705 

potassium  bromide,  to  allay  sexual  excitement,  246. 

protargol,  an  organic  silver  preparation,  441. 

quinine,  applied  locally,  575. 

resorcin,  853. 

silver  citrate,  claimed  to  be  non-irritant  and  actively  germicidal,  438. 

silver  nitrate,  especially  useful  in  chronic  cases,  435. 

silver  sulphocarbolale,  439. 

tariar  emetic,  as  a  diaphoretic,  364. 

terpin  hydrate,  used  internally,  738. 

urotropin,  given  by  mouth  as  urinary  antiseptic,  700. 

zinc  acetate,  428. 

Gonorrhoeal  Cystitis  : 

betol,  852. 

Gonorrhoea!  Rheumatism : 

salicylic  acid,  594. 

Gout  : 

cathartics,  653. 

colchicum,  most  useful  in  typical  gout  (podagra),  653. 

ether,  in  the  collapse  of  retrocedent  gout,  91. 

ichthyol,  as  an  external  application,  528. 

lithium,  supposed  to  be  depurant  and  to  increase  solubility  of  urates,  698. 

magnesia,  antacid  and  laxative,  656. 

piperazine,  occasionally  useful  in  chronic  cases,  699. 

potassium  iodide,  of  some  service  in  irregular  or  chronic  gout,  506. 

salicylates,  used  in  combination  with  colchicum,  594 

sidonal,  used  in  chronic  cases,  701. 

sulphur,  658. 

sulphuretted  hydrogen,  in  chronic  cases,  738. 

treatment  of,  24. 

Gout,  Retrocedent: 

ether,  91. 

Granular  Conjunctivitis : 

See  CONJUNCTIVITIS. 


INDEX   OF   DISEASES.  911 

Granulations,  Exuberant : 

burnt  alum,  caustic  and  astringent,  781. 

copper  sulphate,  antiseptic  astringent  and  mildly  caustic,  781. 

silver  nitrate,  caustic  and  powerfully  germicidal,  435. 

zinc  sulphate,  781. 

Gravel : 

benzoic  acid,  probably  lessens  uric  acid  excretion,  863. 

potassium  acetate,  renders  urine  alkaline,  also  lessens  formation  of  uric  acid, 

693- 

soda,  less  valuable  than  potash  salts,  800. 
water,  679. 

Graves 's  Disease : 

See  EXOPHTHALMIC  GOITRE. 
Grippe  : 

See  INFLUENZA. 
(iummata  : 

See  SYPHILIS. 
Gums,  Retraction  of: 

iodine,  applied  locally  by  means  of  camel's-hair  brush,  504. 

H 

Htematemesis : 

gelatin,   increases  the  coagulability  of  blood,  especially  useful  in  subacute 

cases,  533. 

MonseVs  solution,  one  of  the  most  trustworthy  styptics  in  acute  cases,  449. 
suprarenal  extract  acts  by  constricting  vessels  at  bleeding  point,  542. 
tannic  acid,  404. 
vinegar,  useful  especially  in  emergencies — is  quite  efficient,  397. 

Hcematuria : 

cantharides,  in  atonic  haematuria,  715. 

gallic  acid,  perhaps  the  most  generally  useful  remedy,  406. 

gelatin,  believed  by  some  to  be  irritant  to  kidneys,  is  probably  beneficial,  533. 

turpentine,  in  passive  hemorrhage,  712. 

See  also  BLACK-WATER  FEVER. 

Haemophilia : 

gelatin,  533. 

Haemoptysis : 

alum,  used  by  atomization,  410. 

atomization,  as  a  means  of  applying  remedies  locally  to  lungs,  732. 
cotarnine,  410. 

ergot,  commonly  used,  but  doubtful  if  of  service,  752. 
gallic  acid,  given  internally,  406. 

gelatin,  probably  most  useful  drug  known  (except  opiates);  increases  coag- 
ulability of  blood,  535. 
ipecacuanha,  claimed  to  be  specific,  638. 
lead  acetate,  doubtful  if  of  service,  422. 
MonseVs  solution,  applied  by  atomization,  449. 
oil  of  turpentine,  711. 
opium,  some  form  of  opium  or  morphine  should  always  be  given,  134. 

Hay  Fever : 

ammonium  valeratc,  75. 
antitoxin,  549. 

cocaine,  applied  locally,  relieves  congestion  and  is  anesthetic,  207. 
quinine,  locally  applied,  probably  not  much  value,  575. 
resorcin,  885. 

suprarenal  extract,  probably  the  most  useful  remedy  known  for  local  applica- 
tion, 542. 


912  INDEX    OF   DISEASES. 

Headache : 

ammonia,  when  due  to  sick  stomach,  282. 

ammonium  valerate,  75. 

antacids,  in  gastric  headaches  to  correct  hyperacidity,  798. 

antipyrine,  promptly  acting  coal-tar  analgesic,  609. 

caffeine,  especially  useful  in  conjunction  with  coal  tars,  347. 

camphor,  in  nervous  types,  287. 

emetics,  631. 

ergot,  in  congestive  headaches,  753 

ether,  in  hysterical  or  nervous  cases.  91. 

magnesia,    antacid  laxative  in  cases  with  gastric  disturbances,  656. 

phcnacetin,  one  of  the  most  valuable  of  the  coal  tars,  615. 

strychnine,  when  associated  with  optic  atrophy,  221. 

See  also  MIGRAINE  and  NEURALGIA. 

Heartburn  : 

See  CARDIALGIA. 
Heart  Disease: 

adonidin,  a  heart  stimulant,  355. 

apocynum,  acts  on  the  heart  like  digitalis  but  is  more  diuretic,  334. 

caffeine,  useful  as  a  temporary  stimulant.  348. 

convallaria,  employed  especially  when  dropsy,  350 

digitalis,  the  most  useful  drug  known  in  all  forms  of  prolonged  heart  failure, 

is  both  stimulant  and  tonic  to  heart  muscle,  322. 
Hoffmann's  anodyne,  to  relieve  heart  pains  in  valvular  lesions,  77. 
mercury,  as  an  antiphlogistic  in  acute  endocarditis,  489. 
spartcine,  353. 

strophanthus.  very  similar  to  digitalis,  but  more  prompt  and  less  powerful,  337. 
strychnine,  especially  valuable  where  muscular  weakness  or  degeneration,  222. 
suprarenal  extract,  of  doubtful  utility,  542 
veratrum,  to  allay  overaction  in  excessive  hypertrophy,  369. 
See  also  ENDOCARDITIS,  ANGINA  PECTORIS. 

Heart  Failure  : 

alcohol,  promptly  acting,  not  very  powerful,  304. 

ammonia,  must  be  given  hypodermically  to  have  an  effect,  281. 

amyl  nitrite,  258. 

caffeine,  useful  in  cases  not  too  acute,  348 

camphor,  hypodermic-ally  in  olive  oil,  a  very  powerful   resuscitant,  287. 

digitalis,  323. 

nitroglycerin,  an  overestimated  remedy,  262. 

strophanthus,  337. 

suprarenal  extract,  a  dangerous  drug,  542. 

Heart,  Palpitation  of: 

convallaria,  350. 
sparteine,  353. 

Hemicrania : 

See  MIGRAINE. 
Hem iplegia : 

electricity,  after  symptoms  of  irritation  have  passed  off,  to  exercise  muscles,  56. 

massage,  to  maintain  nutrition  of  muscles,  5. 

strychnine,  avoid  during  early  stages,  later  useful  as  general  tonic,  220. 

Hemorrhage  from  the  Bowels : 

oil  of  erigeron,  highly  recommended,  707. 

oil  of  turpentine,  712. 

suprarenal  extract,  acts  locally  by  constricting  vessels,  542. 

tannic  acid,  best  given  in  form  of  crude  galenical  rather  than  pure  tannin,  404. 

Hemorrhages  : 

alum,  precipitates  albumin  of  blood,  forming  hard  coagulum,  410. 
astringents,  402. 


cocaine,  applied  locally  powerfully  constricts  vessels,  207 
cotarnine,  highly  praised  in  both  internal  and  local  bl 


INDEX   OF   DISEASES.  913 

Is,  207. 

,  --„-  -„   .  bleeding,  410. 

creosote,  useful  only  to  check  capillary  oozing,  844. 
ergot,  widely  used  but  probably  no  good,  752. 

gelatin,  hastens  the  clotting  of  blood,  useful  either  locally  or  internally,  533. 
ipecacuanha,  638. 
lead  acetate,  422. 

matico,  in  external  hemorrhages,  acts  mechanically,  714. 

Monsel's  solution,  a  powerful  styptic  and  astringent  when  locally  applied,  449. 
oil  of  erigeron,  705. 
oil  of  turpentine,  709. 
sulphuric  acid,  453. 

suprarenal    extract,    locally   applied,  a    very    useful    drug,    contracts   blood- 
vessels, 542. 
tannic  acid,  for  local  application,  404. 

Hemorrhoids : 

aloes,  as  a  laxative,  665. 

ancBSthesin,  in  form  of  suppositories,  to  diminish  pain,  118. 
cocaine,  local  anaesthetic  and  constrictor  of  blood-vessels,  207 
cubebs,  used  internally  in  chronic  types,  714. 
enemata,  650. 

glycerin,  used  as  laxative,  791. 
hamamelis,  mildly  astringent,  410. 
infiltration  anesthesia,  for  operative  purposes,  121. 
iodoform,  in  suppositories  a  very  useful  anodyne,  513. 

potassium  chlorate,  saturated  solution  injected  into  the  rectum  a  useful  treat- 
ment, 697, 

stramonium,  in  the  form  of  an  ointment,  anodyne,  185. 
sulphur,  as  a  laxative,  657. 

tannic  acid,  useful  astringent  in  form  of  ointment,  404. 
tobacco,  268. 

Hepatic  Congestion  and  Torpor  : 

ammonium  chloride,  a  useful  remedy  in  chronic  cases,  735. 

calomel,  probably  most  generally  serviceable  remedy  in  acute  cases,  662. 

cathartics,  653. 

chlorine,  826. 

emetics,  633. 

eiwnymus,  used  in  chronic  cases,  655. 

ipecacuanha,  frequently  of  service,  638. 

lemon- juice,  employed  in  habitual  hepatic  torpor,  396. 

nitric  acid,  455. 

nitro-hydrochloric  acid,  one  of  the  best  remedies  in  chronic  cases,  456. 

potassium  salts,  act  as  depurants  by  increasing  oxidation,  693. 

soda,  in  chronic  cases,  800. 

sodium  phosphate,  of  value  in  chronic  cases  with  constipation,  669. 

taraxacum,  of  doubtful  value,  used  in  cases  with  dyspepsia,  530. 

Hepatitis : 

ammonium  chloride,  in  chronic  cases.  735. 
mercury,  as  antiphlogistic  rather  than  purgative,  489. 

nitro-hydrochloric  acid,  in  chronic  cases,  may  be  used  internally  or  in  form 
of  bath,  458. 

Hernia : 

ancesthesia,  82. 

Herpes  : 

naphtol,  in  the  form  of  a  soap,  851. 

Hiccough : 

atropine,  180. 

chloral,  acts  by  depression  of  motor  centres,  152. 
ether,  acts  locally  on  stomach,  also  on  nervous  centres,  91. 

58 


9H  INDEX   OF   DISEASES. 

H  iccough—  Continued : 

musk,  claimed  to  be  almost  a  specific,  74. 
sulphonal,  157. 

High  Arterial  Tension : 

antimony,  powerful  depressant  used  only  in  very  robust  patients,  364. 
nitroglycerin,  employed  especially  in  habitual  conditions,  262. 
veratrum,  used  in  more  or  less  acute  arterial  excitement,  369. 

Hospital  Gangrene : 

bromine,  a  very  active  caustic  and  germicidal  agent,  781. 
nitric  acid,  actively  caustic,  454. 

H  vdrocele : 

iodine,  inject  directly  into  sac,  504. 
phenol,  deep  injections  of,  838. 

Hydrocephalus : 

potassium  iodide,  506. 
Hydrophobia : 

caustic  potash,  applied  to  bite  as  a  prophylactic,  777. 
eschar otics,  776. 

Hyperacidity : 

See  ACIDITY  OF  STOMACH. 
Hyperemesis : 

See  VOMITING. 
Hyperidrosis : 

arsenic,  internally  in  neurotic  cases,  474. 

chalk,  applied  locally  as  a  desiccant,  803. 

tannic  acid,  used  in  form  of  wash,  404. 

tannoform,  astringent  and  antiseptic  dusting  powder,  406. 

See  also  NIGHT-SWEATS. 

Hyperpyrexia : 

See  FEVER. 
Hypertrophy  of  Heart: 

aconite,  382. 
veratrum  viride,  369. 

Hypertrophy  of  Uterus: 

ergot,  754. 
Hypochondriasis : 

alcohol,  307. 
cypripediitm,  79. 

Hysteria : 

anesthetics,  to  check  convulsions,  82. 

antipyrine,  in  convulsive  cases,  607. 

antispasmodics,  73. 

asafetida,  a  useful  nerve  sedative,  76. 

camphor,  useful  as  a  nerve  sedative  and  anticonvulsant,  288. 

cocaine,  as  a  stimulant  and    stomachic,  207. 

conium,  272. 

creosote,  to  check  hysterical  vomiting,  844. 

electricity,  to  cure  local  anaesthesias,  58. 

ether,  given  internally,  91. 

gold  and  sodium  chloride,  497. 

monobromated  camphor,  especially  where  sexual  excitement,  79,  251. 

musk,  74. 

oil  of  wormseed,  807. 

potassium  bromide,  one  of  the  most  widely  used  of  all  remedies,  245. 

sodium  bromide,  248. 


INDEX   OF    DISEASES.  915 

sparteinc,  353. 

sumbul,  especially  in  cases  with  uterine  disturbances,  80. 
valerian,  a  mildly  acting  but  widely  useful  drug,  75. 
validol,  a  combination  of  valeric  acid  and  menthol,  75. 
valyl,  a  synthetic  preparation  of  valeric  acid,  75. 

Hysterical  Paralysis : 

electricity,  54. 

I 
Ichthyosis  : 

naphtol,  851. 

Idiocy : 

thyroid  extract,  valuable  probably  only  in  myxcedematous  subjects,  537. 

Ileus : 

See  INTESTINAL  OBSTRUCTION. 

Impotence : 

turpentine,  712. 

yohimbinc,  useful  only  in  neurasthenic  cases,  not  in  organic,  715. 

Incontinence  of  Urine : 

antipyrine,  in  spasmodic  cases,  606. 

atropine,  when  due  to  irritability  of  bladder,  180. 

chloral,  in  spasmodic  cases,  152. 

quinine,  in  large  doses  frequently  useful,  572. 

strychnine,  when  due  to  nervous  relaxation,  222. 

turpentine,  in  atonic  forms,  712. 

Indigestion : 

See  DYSPEPSIA. 
Infantile  Colic: 

See  COLIC. 
Infantile  Convulsions: 

See  CONVULSIONS. 
Infantile  Diarrhoea: 

See  CHOLERA  INFANTUM. 
Infantile  Paralysis: 

electricity,  not  to  be  used  until  inflammatory  symptoms  have  passed  off,  56. 
massage,  5. 

Inflammations : 

belladonna,  locally  applied  as  anodyne,  182. 

blisters,  useful  in  serous  and  other  internal  inflammations,  768. 

carbolic  acid,  deep  injections  in  deep-seated  inflammations  of  chronic  type,  838. 

cold,  in  acute  stage,  30. 

lead  acetate,  sedative  astringent  embrocation,  especially  in  acute  conditions,  422. 

mercury,  especially  valuable  in  serous  inflammations,  may  be  used   internally 

or  externally,  488. 

opium,  seems  to  exercise  a  specific  antiphlogistic  effect,  134. 
silver  nitrate,  applied  locally  to  inflamed  mucous  membranes,  435. 
solution  of  lead  subacetate,  422. 

stramonium,  used  for  same  purposes  as  belladonna,  185. 
tartar  emetic,  to  quiet  arterial  excitement  in   sthenic  inflammations,  364. 

Influenza : 

aconite,  to  encourage  sweating,  383. 

betanaphtol,  849. 

eupyrin,  for  relief  of  pains,  608. 

pilocarpine,  used  to  produce  sweat  will  sometimes  abort,  726. 

salipyrin,  to  allay  pain  and  fever,  617. 


916  INDEX   OF    DISEASES. 

Insanity  : 

chloretone,  used  as  a  somnifacient,  uncertain,  162, 

hyoscine  hydrobromide,  acts  as  hypnotic  and  in  some  cases  seems  to  have 

curative  effect,  189. 

hyoscyamus,  is  similar  but  inferior  to  hyoscine,  186 
paraldehyde ,  one  of  the  most  valuable  somnifacients,  161. 
spleen  extract,  544. 
veronal,  as  a  hypnotic,  164. 
See  also  MANIA. 

Insomnia : 

See  SLEEPLESSNESS. 

Intermittent  Fever: 

See  MALARIA. 

Intertrigo : 

clialk,  protective  tind  desiccant,  803. 
ichthyol,  527. 

Intestinal  Atony : 

physostigma,  the  most  useful  stimulant  to  unstriped  muscle  fibre  known,  237 
strychnine,  222. 

Intestinal  Catarrh  : 

ammonium  chloride,  in  chronic  cases.  734. 

Calabar  bean,  237. 

cathartics,  to  cleanse  the  bowel  from  irritant  substance,  650. 

forced  enemata,  650. 

hydrastis,  in  chronic  cases,  especially  if  of  alcoholic  origin,  760. 

naphtalin,  as  an  antiseptic,  850. 

salol,  intestinal  antiseptic,  847. 

tannalbin,  405. 

See  also  ENTERITIS. 

Intestinal  Indigestion  : 

betanaphtol,  to  check  fermentation,  851. 
physostigma,  237. 
salol,  847. 

Intestinal  Obstruction  : 

atropine,  when  due  to  intestinal  spasm,  180. 
opium,  in  spasmodic  or  irritative  types,  134. 

Iritis  and  Irido-cyclitis : 

atropine.  to  rest  eye  and  prevent  adhesions,  best  mydriatic  for  this  purpose 

183. 

dionine,  increases  the  flow  of  lymph  in  eye,  144. 
mercury,  in  cases  with  marked  lymphatic  exudation.  489. 

salicylic  acid,  especially  but  not  exclusively  useful  in  rheumatic  persons,  594. 
santonin,  in  amaurosis  following  iritis,  809. 
thiosinamine,  probably  of  very  little  value,  530 

Irritable  Bladder: 

See  BLADDER,  IRRITABLE 

Irritable  Heart: 

digitalis,  325. 

Itch: 

See  SCABIES. 

Ivy-Poisoning: 

See  RHUS-TOXICODENDRON  POISONING. 


INDEX   OF    DISEASES.  91; 

J 
Jaundice : 

ammonium  chloride,  in  chronic  torpor  of  the  liver  and  catarrhal  jaundice,  735. 

emetics,  to  relieve  portal  congestion,  633. 

forced  enemala,  650 

ipecacuanha,  638. 

lemon  juice,  in  catarrhal  jaundice,  396. 

mercury,  probably  the  most  generally  serviceable  drug  in  catarrhal  jaundice 

and  acute  biliousness,  662. 
nitro-hydrochloric   acid,  especially    valuable    in   cases    depending  on   chronic 

hepatic  torpor,  456. 

oxgall,  most  powerful  stimulant  to  hepatic  secretion  known,  655. 
potassium  bicarbonate,  691. 
potassium  salts,  depurant  and  alkaline;  useful  in  chronic  hepatic  torpor  and 

catarrhal  jaundice,  693. 

sodium  phosphate,  in  chronic  cases  with  constipation,  669. 
sodium  salts,  alkalies  of  value,  800. 

Joints,  Inflammation  of : 

blisters,  in  chronic  cases,  768. 

cautery,  769 

cod-liver  oil,  in  tuberculous  joint  diseases,  517. 

ichthyol,  especially  in  gouty  or  rheumatic  forms,  528. 

iodine,  externally  as  alterative  and  counter-irritant,  504. 

iodoform,  injected  into  the  joint  directly,  in  tuberculous  arthritis,  513. 

lithium,  in  gouty  or  rheumatic  patients,  698. 

massage,  when   traumatic  in  origin,  5. 

mercurial  plaster,  493. 

K 

Keloid : 

ichthyol,  locally  applied,  527. 

thiosinamine,  may  be  used  either  internally  or  injected  locally,  530. 

thyroid  extract,  recommended  highly  for  internal  use,  538. 

Keratitis : 

atr opine,  to  lessen  liability  to  iritis,  183. 

dionine,  increases  lymph  flow  in  eye,  144. 

iodipin,  508. 

physostigmine,  to  reduce  vascularization,  237. 

salicylic  acid,  especially,  but  not  exclusively,  useful  in  rheumatic  cases,  594. 

Kidneys,  Congestion  of: 

flaxseed,  sedative,  useful  in  acute  conditions,  784. 
gin,  use  in  chronic  conditions,  avoid  in  acute,  707. 
sweet  spirit  of  nitre,  feebly  diuretic,  686. 

L 
Labor: 

anaesthetics,  to  allay  the  suffering,  8 1 . 

chloral,  to  lessen  pain  and  overcome  rigidity  of  os,  152. 

ergot,  to  increase  uterine  contractions,  used  only  in  latter  stages,  750. 

Laryngismus  stridulus : 

antipyrine,  608. 
atr  opine,  180. 
chloral,  152. 
expectorants,  731. 

Laryngitis : 

camphor-menthol,  dissolved  in  liquid  petrolatum  and  used  as  spray,  (note)  852. 
cocaine,  applied  locally  as  palliative,  207. 
gelsemium,  internally  in  spasmodic  types,  267. 
glycerin,  791. 


9i8  INDEX   OF   DISEASES. 

Laryngitis  —  Continued  : 

heroine,  used  as  local  anaesthetic  in  laryngeal  tuberculosis,  145 

•ichthargan,  a  solution  in  glycerin  as  a  spray,  440. 

mercury,  administered  internally  as  antiphlogistic,  489. 

naphtol,  851. 

orthoform,  a  valuable  local  anaesthetic  in  tuberculous  laryngitis,  118. 

pilocarpine,  728. 

silver  nitrate,  two  per  cent  solution  applied  locally,  435 

suprarenal  capsule,  541. 

Lead  Poisoning: 

alum,  recommended  in  colica  pictonum,  410 

atropine,  most  valuable  remedy  for  lead  colic  known,  180. 

electricity,  for  local  palsies  in  chronic  cases,  56. 

potassium  iodide,  to  increase  elimination  of  lead  in  chronic  poisoning,  506. 

strychnine,  of  value  in  plumbic  poliomyelitis.  220,  222. 

sulphuric  acid,  chemical  antidote,  453. 

treatment  of  acute,  412. 

treatment  of  chronic,  418. 

Lepra : 

ammonium  iodide,  507. 
ichthyol,  527. 
thiosinamine ,  530. 

Leucorrhoea : 

aluminum  sulphate,  astringent  and  antiseptic,  but  irritant,  411. 

bismuth  subnitrate.  sedative  astringent,  425. 

creosote,  disinfectant,  844 

ferric  ammonium  sulphate,  actively  astringent,  451. 

iodine,  tincture  of.  locally  applied,  504, 

potassium  permanganate,  disinfectant  and  deodorant,  827. 

resorcin,  855 

tannic  acid,  astringent,  404 

Leukaemia : 

bone-marrow,  probably  not  of  value,  531. 

cacodylic  acid,  of  no  more  value  than  official  forms  of  arsenic,  482. 

cold  douche,  over  splenic  area,  32. 

ergot,  injected  hypodermically.  752. 

spleen  extract,  531. 

Lichen  : 

arsenic,  473. 

Lipoma  : 

ichthyol,  528. 

Lithaemia : 

See  URIC  ACID  DIATHESIS. 
Liver  Diseases  : 

See  HEPATIC. 
Local  Anaesthesia: 

eletricity,  in  form  of  electrical  brush,  58. 
Local  Paralysis : 

massage,  5. 
Locomotor  Ataxia  : 

acetanilid,  for  relief  of  pain,  614. 

anlipyrine,   for  painful  crises,  608 

aspirin,  as  analgesic,  598. 

glycero-phosphat.es,  as  nerve  tonic,  519. 

hyoscine,  as  analgesic,  189. 

rheumatine,  579. 

silver  nitrate,  used  to  affect  conditions  in  cord,  but  of  doubtful  service,  436. 


INDEX   OF   DISEASES.  919 

Lumbagc: 

cod-liver  oil,  in  chronic  cases  with  cachexia,  490. 
ichthyol,  applied  locally,  527. 
potassium  iodide,  in  subacute  types,  506. 
salicylates,  the  standard  remedy,  592. 
sulphur,  657. 

Lumbrici : 

See  ROUND- WORMS. 
Lupus : 

aristol,  as  a  dusting  powder,  515. 

arsenic,  used  internally,  778. 

arsenic  iodide,  as  an  external  application,  482. 

cantharidin,  (note)  771. 

guaiacol,  actively  germicidal,  846. 

ichthyol,  527. 

phosphorus,  internally  as  a  tonic  alterative,  461. 

pyrogallol,  an  ointment  used  as  a  caustic,  781. 

red  mercuric  iodide.  496. 

thiosinamine,  530. 

thyroid  extract,  537. 

Lymphadenitis : 

ichthyol,  applied  externally  in  form  of  ointment,  528. 
sulphurated  lime,  used  internally,  647. 
See  also  SCROFULOSIS. 

L\  mphoma : 

arsenic,  473. 

M 
Malaria : 

ammonia,  as  a  heart  stimulant  in  malarial  collapse,  281. 

ammonium  chloride,  not  of  much  service,  735. 

amyl  nitrite,  will  abruptly  end  a  chill;  perhaps  useful  in  pernicious  type,  258. 

apiol,  not  of  much  value.  744. 

aristochin,  an  almost  tasteless  ester  of  quinine,  579. 

arsenic,  useful  especially  in  chronic  or  irregular  malarias;  also  in  convalescence 

from  acute  ague,  472. 

chloroform,  may  be  used  to  abort  a  chill,  99. 
cinchonine.  similar  to  but  less  powerful  than  quinine.  578. 
counter-irritants,  in  the  collapse  of  pernicious  malaria,  768. 
diaphoretics,  to  shorten  duration  of  paroxysm,  719 
eucalyptus,  frequently  of  service  when  quinine  contraindicated,  584. 
euquinine,  a  tasteless  substitute  for  quinine,  579. 
gefsemium,  266. 
methylene-blue,    a    very    powerful    antiperiodic,     especially     valuable     where 

haematuria,  581. 
piperin,  628. 

potassium  salts,  in  hepatic  disturbances,  693. 

quinine,  the  standard  remedy,  best  given  immediately  before  paroxysm,  572. 
saloquinine,  580. 
Warburg's  tincture,  probably  the  most  effectual  combination  known  against 

the  more  severe  types  of  the  disease,  579. 

Malarial  Neuralgia: 

arsenic,  as  an  adjunct  to  cinchona  alkaloids,  473 

electricity,  probably  of  little  value,  57. 

quinine,  large  doses  required  to  produce  an  effect,  574. 

Malignant  Pustule: 

escharotics,  776. 
Mania : 

atropine,  when  disease  dependent  on  exhaustion,  as  puerperal  mania,  181. 
cathartics,  as  revulsants,  653. 


920  INDEX   OF   DISEASES. 

Mania —  Continued  : 

chloral,  for  its  somnifacient  effect,  150. 
conium,  to  lessen  the  motor  excitement,  272. 
croton  oil,  as  a  revulsant,  674. 
gelsemium ,  267. 

hyoscine  hydrobr ornate,  seems  to  have  some  curative  effect  as  Well  as  general 
sedative  action,  189. 

Mania  a  Potu : 

See  DELIRIUM  TREMENS 

Mastitis : 

belladonna  plaster,  182. 

Masturbation : 

heroine,  claimed  to  be  a  sexual  sedative,  145. 

potassium  bromide,  the  most  generally  serviceable  sexual  sedative  known,  246. 

Melancholia : 

alcohol,  will  often  relieve  symptoms,  but  great  danger  of  habit,  307. 

cocaine,  of  very  little  service,  207. 

thyroid  extract,  may  be  tried,  but  not  likely  to  be  successful,  537. 

Membranous  Croup : 

See  CROUP. 

Meniere's  Disease : 

pelletierine,  813. 

Meningitis : 

cautery,  the  most  active  form  of  counter-irritation,  769. 

cold,  ice  bag  to  the  head,  31. 

electricity,  contraindicated  in  the  acute  stages,  56. 

Menorrhagia : 

aloes,  when  constipation;  acts  as  laxative  and  tends  to  pelvic  hyperaemia,  665. 

calcium  phosphate,  when  associated  with  anaemia,  520. 

cotarnine,  410 

creosote,  applied  locally,  844. 

digitalis,  claimed  to  act  as  a  stimulant  to  uterine  muscles,  328. 

ergot,  perhaps  the  most  generally  efficient  remedy  known,  752 

gelatin,  increases  coagulability  of  blood,  may  be  used  both  internally  and 

locally,  533 

hydrastinine  hydrochlorate,  probably  acts  by  causing  contraction  of  womb,  763. 
mammary  glands,  extract  of,  53 1 . 
oil  of  erigeron,  707. 

savine,  useful  only  in  conditions  of  relaxation,  742. 

suprarenal  extract,  given  internally,  probably  causes  uterine  contraction,  543. 
thyroid  extract,  537. 
viburnum.  744. 

Menstruation,  Suppression  of : 

See  AMENORRHCEA. 

Mercurial  Ptyalism : 

See  PTYALISM. 

Metritis : 

bismuth  oxyiodogallate ,  employed  in  form  of  suppositories,  426. 
creosote,  as  a  disinfectant,  especially  in  puerperal  cases,  844. 
ergot,  in  chronic  cases,  754. 

Metrorrhagia : 

ergot,  acts  by  stimulating  uterine  muscle,  752. 

felatin,  increases  coagulation  of  blood,  533. 
ydrastinine  hydrochlorate,  763. 


INDEX   OF   DISEASES.  921 

Migraine : 

acetopyrin,  coal-tar  analgesic,  610. 

amyl  nitrite,  in  cases  with  spasm  of  capillary  blood-vessels,  258. 

antipyrine,  during  paroxysm,  to  relieve  headache,  608 

caffeine,  sometimes  promptly  relieves  headache,  at  others  fails,  347. 

cannabis  indica,  used  as  curative  between  paroxysms,  195. 

cocaine,  207 

electricity,  of  little  service,  57. 

gold  bromide,  250. 

salipyrin,  used  to  relieve  headache,  617. 

thermal,  analgesic  of  coal-tar  series,  618. 

validol,  75. 

Mitral  Disease : 

See  HEART  DISEASE. 

Morphine-Poisoning  : 

See  OPIUM-POISONING. 

Morphoea : 

arsenic,  474. 

Multiple  Sclerosis : 

acetanilid,  614. 

Muscarine  Poisoning : 

atropine,  counteracts  effects  of  poison  on  inhibitory  and  secretory  nerves,  182. 
digitalis,  as  heart  stimulant,  327. 

Muscular  Rheumatism : 

aconite,  to  produce  sweating,  especially  in  conjunction  with  pilocarpine,  383. 

diaphoretics,  719. 

Dover's  powder,  encourages  sweating  and  relieves  pain,  729. 

ichthyol,  applied  locally,  528. 

massage,  5. 

pilocarpine,  to  produce  sweating,  726. 

potassium  iodide,  in  subacute  or  chronic  cases,  505. 

sulphur,  657. 

Myelitis : 

electricity,  avoid  during  inflammatory  stage,  later  useful  to  restore  muscular 

tone,  56. 

phosphorus,  as  a  reconstructive  tonic  for  nerve  centres,  617. 
silver  nitrate,  value  questionable.  436. 

Myocarditis : 

See  HEART  DISEASE. 
Myopathy : 

thyroid  extract,  538. 
Myxcedema : 

thyroid  extract,  is  a  specific,  537. 

N 
Narcotic  Poisoning : 

See  POISONING. 
Nasal  Catarrh : 

See  RHINITIS. 

Nausea : 

See  SICK  STOMACH. 
Nephritis : 

See  BRIGHT'S  DISEASE. 


922  INDEX   OF   DISEASES. 

Nervous  Exhaustion  : 

See  NEURASTHENIA. 

Nervous  Vomiting : 

See  VOMITING. 

Nervousness : 

asafetida,  in  cases  of  hysterical  type,  76. 

camphor,  a  very  useful  sedative,  287. 

potassium  bromide,  the  most  reliable  sedative  except  in  hysterical  cases,  245. 

valerian,  useful  in  milder  forms  of  hysteria,  75. 

Neuralgia : 

aconite,  applied  locally,  383. 

alcohol,  grave  danger  of  formation  of  habit,  307. 

ammonium  chloride,  formerly  used  in  ovarian  neuralgia,  not  generally  effica- 
cious. 735 

antipyrine,  one  of  the  best  analgesics,  608. 

arsenic,  especially  but  not  exclusively  useful  in  malarial  cases,  474. 

aspirin,  of  service  in  nervous  a?  well  as  rheumatic  types,  598. 

blisters,  768. 

butyl  chloral- hydrate.  166 

caffeine,  very  markedly  increases  the  analgesic  power  of  other  antineuralgics, 
especially  the  coal-tar  products,  347. 

cannabis  indica,  used  both  as  an  anodyne  and  as  a  curative,  195. 

carbon  disulphide,  employed  locally  as  a  counter-irritant.  775. 

chloroform,  in  the  form  of  a  liniment,  99. 

cod-liver  oil,  518. 

croton  chloral.  166. 

electricity,  not  useful  when  organic  lesion  or  toxic  cause.  57. 

ether,  internally  sometimes  of  service,  91. 

gelsemium,  used  especially  as  a  curative  agent  in  recurring  neuralgias,  267. 

gold  and  sodium  chloride,  497. 

Jiydrocyanic  acid,  in  neuralgia  of  the  stomach,  392. 

iodoform.  when  syphilitic  origin,  510. 

methylene-blue,  not  so  useful  as  other  aniline  derivatives,  578. 

oil  of  peppermint,  applied  locally  over  painful  area,  counter-irritant  and  anaes- 
thetic, 631. 

phosphorus,  when  due  to  nervous  exhaustion,  461. 

potassium  bromide,  very  frequently  of  service,  especially  in  combination  with 
caffeine,  245. 

potassium  iodide,  in  rheumatic  or  syphilitic  cases,  506. 

pyrosal,  combination  of  antipyrin  and  salicylic  acid,  618. 

quinine,  especially  in  periodic  types,  even  if  not  malarial,  574. 

saloquinine,  580. 

thermal,  618. 

veratrine,  used  externally  in  form  of  ointment,  but  is  a  dangerous  remedy,  372. 

See  also  HEADACHE. 

Neuralgia,  Intermittent : 

See  MALARIAL  NEURALGIA. 

Neuralgia,  Rheumatic : 

See  RHEUMATIC  NEURALGIA. 

Neurasthenia : 

bromipin,  a  preparation  of  bromide,  251. 

bromolein,  251. 

cocaine,  as  a  nerve  stimulant  and  tonic,  207. 

digitalis,  when  circulation  is  feeble,  327. 

euquinine,  as  general  tonic,  579. 

glycero-phosphates,  supposed  to  represent   phosphorus  in  easily  assimilable 

form,  but  of  unproved  value,  519. 

gold  and  sodium  chloride,  used  as  nerve  alterative,  value  doubtful,  497. 
hops,  mildly  sedative,  useful  in  nervous  unrest,  77. 
hypophosphites,  521. 


INDEX   OF   DISEASES.  923 

paraldehyde,  as  a  hypnotic,  161. 

phosphorus,  increases  reconstructive  metabolism  of  nerve  centres,  frequently 

of  great   service,  460. 
rest-cure,  17. 

sparteine,  to  relieve  cardiac  palpitation,  353. 
strychnine,  especially  useful  in  chronic  cases,  222. 
treatment  of,  16. 

validol,  a  nerve  sedative  of  valerian  group,  75. 
valyl,  75. 
Warburg's  tincture,  in  acute  nervous  exhaustion,  579. 

Neuritis : 

acetopyrin,  to  lessen  pain,  608. 

aconite,  rarely  of  value,  may  be  used  locally,  383. 

atropine,   in  cases  with  local  muscular  spasm,  180. 

blisters,  the  most  generally  useful  form  of  counter-irritation,  repeat  frequently 

as  necessary,  768. 

cautery,  often  valuable  in  chronic  cases,  769. 

electricity,  use  galvanic  current,  but  not  during  active  inflammatory  stage,  57. 
methylene-blue,  to  relieve  pain,  581. 

rheumatine,  a  combination  of  salicylic  acid  and  quinine,  579. 
salicylates,  in  rheumatic  cases,  594. 
saloquinine,  combination  of  quinic  and  salicylic  acids,  580. 

Night-Pains,  Syphilitic : 

iodoform,  510. 
Night-Sweats : 

agaric,  a  very  frequently  useful  remedy,  409. 

alum,  to  be  employed  externally,  410. 

atropine,  the  most  generally  serviceable  remedy  known,  181. 

camphoric  acid,  288. 

dionine,  especially  useful  in  phthisis,  as  it  is  also  cough  sedative,  143. 

ergot,  in  cases  with  passive  relaxation  of  blood-vessels,  752. 

gallic  acid,  406. 

sulphonal,  157.  • 

sulphuric  acid,  one  of  the  best  remedies,  453. 

Nipples,  Sore: 

benzoic  acid,   best  applied  in  form  of  compound  tincture  of  benzoin,  antiseptic 

and  protective,  863. 
tannic  acid,  for  purpose  of  hardening,  404. 

Nocturnal  Emissions  : 

See  SPERMATORRHOSA. 
Nocturnal  Enuresis : 

See  INCONTINENCE  OF  URINE. 
N ymphomania : 

heroine,  recommended  as  sexual  sedative,  145. 

hyoscine  hydrobromate ,  has  especial  action  on  sexual  centres,  189. 

potassium  bromide,  in  conjunction  with  hyoscine  most  efficacious  remedy,  246. 

O 
Obesity : 

saccharin,  as  a  sweetening  agent  free  from  objections  to  sugar,  792. 

treatment  of,  20. 

thyroid  extract,  will  reduce  weight  temporarily  more  certainly  than  any  other 

drug,  537. 
Obstruction  of  Bowels: 

See  INTESTINAL  OBSTRUCTION. 
(Edema  of  the  Lungs : 

strophanthus,  337. 

See  also  DROPSY. 


924  INDEX   OF   DISEASES. 

(Esophagus,  Stricture  of: 

anaesthetics,  when  spasmodic  origin,  82. 

Onychia  Maligna : 

corrosive  sublimate,  powerfully  germicidal,  mildly  caustic,  779. 
lead  nitrate,  to  be- powdered  on  inflamed  area,  423. 

Ophthalmia : 

iodine,  used  in  scrofulous  cases,  504. 

salicylic  acid,  in  sympathetic  ophthalmia,  594. 

silver  acetate,  in  ophthalmia  neonatorum,  438. 

Opium- Habit  : 

cocaine,  207. 
treatment  of,  135. 

Opium-Poisoning : 

atropine,  as  respiratory  stimulant,  181. 
caffeine,  respiratory  and  cerebral  excitant,  347. 
potassium  permanganate,  as  chemical  antidote,  827. 
treatment  of,  135. 

Osmidrosis : 

tannic  acid,  404. 

Osteomalacia : 

calcium  phosphate,  520. 
phosphorus,  461. 

Osteoporosis  : 

phosphorus,  461. 

Otitis  : 

betanaphtol,  as  an  antiseptic,  851. 
resorcin,  in  chronic  cases,  855. 

Otorrhcea  : 

creosote,  as  a  disinfectant  in  fetid  types,  844. 
hydrastin,  acts  directly  on  mucous  membrane,  760. 
potassium  permanganate,  oxidizing  disinfectant,  827. 

Ovarian  Irritation  : 

gold  and  sodium  chloride,  in  conditions  of  lowered  nervous  power,  497. 
viburnum,  744. 

Ovarian  Neuralgia: 

ammonium  chloride,  of  doubtful  service,  735. 

gelsemium,  acts  beneficially  in  some  unknown  manner,  267. 

gold  and  sodium  chloride,  49  7 . 

Over-Secretion : 

astringents,  when  due  to  relaxed  condition,  402. 
tannic  acid,  404. 

Oxalic  Acid  Diathesis : 

nitric  acid,  455. 

nitro-hydrochloric  acid,  a  specific  in  neurasthenic  oxaluria,  455. 

Oxalic- Acid  Poisoning: 

treatment  of,  398. 
Oxyuris  Vermicularis : 

See  SEAT-WORMS. 
Ozsena : 

iodine,  an  alterative  stimulant,  504. 
potassium  permanganate,  disinfectant,  827. 


INDEX   OF   DISEASES.  925 


Pain: 

acetanilid,  when  pain  of  nervous  origin,  614. 

aconite,  locally  applied  in  neuralgia  arid  similar  conditions,  383. 

anaesthetics,  of  service  in  severe  medical  as  well  as  surgical  conditions,  8r. 

antipyrine,  in  various  nervous  pains  whether  functional  or  organic,  608. 

atropine,  as  local  anodyne,  180. 

cannabis  indica,  frequently  of  service  although  not  very  powerful,  195. 

chloral,  of  little  use  as  analgesic,  152. 

chloroform,  externally  as  counter-irritant,  99. 

Dover's  powder,  729. 

electricity,  useful  in  neuralgic,  not  in  organic  pains,  57. 

exalgine,  617. 

iodofornt,  as  a  local  anaesthetic,  510. 

methylene-bhte,  similar  to,  generally  less  useful  than  other  aniline  derivatives, 

581. 

oil  of  peppermint,  locally  anaesthetic  and  counter-irritant.  622. 
opium,  the  most  generally  efficient  drug,  but  danger  of  habit,  135. 
phenacetin,  useful  in  nervous  pains,  especially  in  combination  with  caffeine, 

615- 

Palpitation  of  Heart : 

See  HEART,  PALPITATION  OF. 

Papilloma : 

resorcin,  855. 

Paralysis : 

electricity,  not  to  be  used  during  inflammatory  stages,  56. 
strychnine,  useful  only  when  depressant  poison  is  cause,  222. 
veratrine,  applied  as  counter-imtant  over  the  spine,  372. 

Paralysis  Agitans: 

conium,  272. 

hyoscine..  a  useful  palliative,  189. 

Paraplegia,  Myelitic : 

phosphorus,  may  be  of  service,  461 . 
silver  nitrate,  probably  of  no  value,  436 

Parturition : 

See  LABOR. 

Pemphigus  : 

arsenic,  473. 

Pericardial  Effusions: 

See  EFFUSION,  PERICARDIAL. 

Pericarditis : 

mercury,  when  exudate  is  fibrinous   489. 

potassium  iodide,  in  cases  with  serous  effusion,  506. 

Peritonitis : 

blisters,  768. 

cold,  applied  to  abdomen,  31. 

iodoform,  in  tuberculous  peritonitis,  513. 

mercury,  in  sthenic  forms  of  puerperal  peritonitis  or  where  fibrinous  exudate, 

489. 
opium,  very  useful  for  its  antiphlogistic  action  as  well  as  checking  intestinal 

peristalsis,  134 

poultices,  a  useful  means  of  applying  heat,  792,  793. 
veratrum,  acts  almost  specifically,  its  tendency  to  vomit  must  be  controlled  by 

opium,  369 


926  INDEX    OF   DISEASES. 

Pernicious  Anaemia : 

bone-marrow,  may  be  tried,  53 1 . 
iron,  of  very  little  service,  447. 

Pernicious  Fever  i 

See  MALARIA. 
Pertussis : 

See  WHOOPING-COUGH. 
Petit  Mai : 

amyl  nitrite,  as  a  diagnostic  agent,  259. 

chloretone,  162. 

potassium  bromide,  less  generally  of  service  than  in  true  epilepsy,  246. 

Phagedaena : 

nitric  acid,  as  a  caustic,  780. 
Phantom  Tumor: 

Calabar  bean,  acts  by  stimulating  intestinal  muscles,  231. 
Pharyngitis : 

suprarenal  extract,  to  overcome  congestion,  542. 
Phenol-Poisoning : 

treatment,  840. 
Phlegmons : 

ichthargan,  applied  in  form  of  ointment,  440. 

phenol,  deep  injections  of  value,  838. 

Phosphatic  Gravel : 

bcnzoic  acid,  863. 
Phosphaturia : 

benzoic  acid,  to  prevent  precipitation  of  phosphates  from  urinary  fermentation, 

863. 

glycero-phosphoric  acid,  when  daily  elimination  of  phosphorus  is  excessive,  519. 
urotropin,  as  a  urinary  antiseptic,  700. 

Phosphorus-Poisoning : 

treatment  of,  466. 
Phthisis : 

alcohol,  of  value  as  an  accessory  food  and  stimulant  to  digestion,  307. 

ammonium  iodide,  as  a  resolvent  in  incipient  cases,  507. 

antipyrine,  to  control  the  fever,  607. 

arsenic,  in  fibroid  or  slowly  progressing  types.  474. 

calcium  phosphate,  520. 

camphoric  acid,  to  check  the  night-sweats,  288. 

cannabis  indica,  as  a  euthanasiac,  195. 

canlharidin,  (note)  771. 

cocaine,  as  a  local  application  in  irritated  throat  conditions,  207. 

codeine,  to  check  the  cough,  142. 

cod-liver  oil,  of  service  on  account  of  food  value  and  perhaps  through  some 

specific  action,  517. 

creosote,  acts  as  a  stimulant  expectorant,  843 
creosote  carbonate,  asserted  to  be  less  injurious  to  the  stomach  than  creosote, 

845- 

formaldehyde,  has  been  employed  by  inhalation  with  doubtful   benefit,  850. 
gallic  acid,  to  lessen  the  night-sweats,  406. 
guaiacol,  as  a  stimulant  expectorant,  846. 

neroine,  perhaps  the  most  generally  useful  cough  sedative  known,  145. 
hyppphosphites,  520. 

iodine,  applied  externally  as  a  counter-irritant,  503. 
prunus  virginiana,  used  for  cough,  but  very  feeble,  622. 
sulphuretted  hydrogen,  an  active  but  unpleasant  expectorant. 
theocol,  845. 
tuberculin,  its  precise  value  as  a  curative  agent  is  uncertain,  544. 


INDEX    OF    DISEASES.  927 

Piles  : 

See  HEMORRHOIDS. 

Pityriasis : 

oil  of  cajnput,  629. 
res  or  tin,  855. 

Pleurisy  : 

atropine,  as  a  circulatory  stimulant  in  conditions  of  collapse,  181. 

blisters,  their  counter-irritant  effect  often  of  service,  768. 

cold,  applied  over  chest,  3 1 . 

gelsemium,  266. 

iodine,  applied  externally  in  chronic  cases  with  serous  effusion,  504. 

mercury,  beneficial  in  cases  with  fibrinous  exudate,  489. 

potassium  iodide,  when  serous  effusion  is  present,  477. 

poultices,  the  whole  chest  may  be  covered,  794. 

salicylic  acid,  recommended  as  diuretic  in  pleural  effusion,  594. 

Pleuritic  Effusion : 

See  EFFUSION,  PLEURAL. 

Pneumonia : 

aconite,  in  the  early  stages  as  a  cardiac  sedative  not  so  good  as  veratrum,  .383. 

alcohol,  as  a  cardiac  stimulant,  305. 

ammonia,  used  as  an  expectorant  with  doubtful  advantage,  282. 

antipyrine,  to  lessen  fever,  607. 

arsenic,  in  chronic  or  fibrous  pneumonia,  474. 

atropine,  as  a  circulatory  stimulant,  181. 

blisters,  766. 

camphor,  used  hypodermically  is  a  very  useful  cardiac  stimulant  in  emer- 
gencies, 287. 

cold,  31,  37. 

cold-water  compresses,  preferable  to  hot  applications  when  temperature  is 
high,  795. 

digitalis,  as  heart  stimulant,  especially  valuable  in  later  stages,  327. 

ergot,  used  in  the  early  stages,  7  53 . 

gelsemium,  266. 

guaiacol,  used  as  antipyretic,  but  is  dangerous,  846. 

mercury,  489. 

musk,  as  a  nervous  stimulant  in  adynamic  forms,  74. 

naphtol,  oily  solution  dropped  into  trachea,  851. 

oil  of  turpentine,  as  a  counter-irritant  application.  711. 

phosphorus,  for  the  nerve  exhaustion  in  adynamic  cases,  462. 

poultices,  794. 

respiratory  stimulants,  277. 

tartar  emetic,  to  reduce  circulatory  excitement,  364. 

theocol,  847. 

veratrum  viride,  useful  in  early  stages  to  diminish  the  congested  area,  369. 

Poisoning : 

alcohol,  as  cardiac  stimulant,  306. 

ammonia,  hypodermically.  as  circulatory  stimulant,  281. 
apomorphine,  as  emetic,  642. 

atropine,  as  a  respiratory  and  circulatory  stimulant,  181. 
heat,  to  combat  collapse,  30. 
ipecacuanha,  as  an  emetic,  637. 

mustard,  a  prompt  and  efficient  but  unpleasant  emetic,  643. 
physiological  salt  solution,  useful  to  maintain  circulation  and  increase  elimi- 
nation, 209,  679. 

strychnine,  probably  most  powerful  respiratory  stimulant  known,  222. 
zinc  sulphate,  the  most  generally  useful  emetic  in  poisoning,  643. 

Poisonous  Fungi : 

atropine,  the  physiological  antagonist  of  muscarine,  182. 
Poliomyelitis,  Acute : 

See  INFANTILE  PARALYSIS. 


928  INDEX   OF   DISEASES. 

Polyuria : 

exalgine,  615. 

See  also  DIABETES  IXSIPIDUS. 

Post-partum  Hemorrhage : 

ergot,  acts  by  causing  uterine  contractions,  most  valuable  remedy  known,  751. 
ipecacuanha,  supposed  to  affect  coagulability  of  blood,  638. 

Pregnancy : 

calcium  phosphate,  as  a  prophylactic  against  foetal  rickets,  520. 

cerium  oxalate,  for  vomiting,  427. 

confection  of  senna,  useful  as  a  laxative,  667. 

ipecacuanha,  for  the  relief  of  vomiting,  637. 

Prolapse  of  Rectum : 

strychnine,  222. 
Prurigo : 

hydrocyanic  acid,  a  local  anaesthetic  used  to  allay  itching,  394. 
naphtol,  used  in  form  of  soap  as  antiseptic,  851 . 

Pruritus  : 

anoesthesin,  used  in  form  of  ointment,  118. 

brucine,  227. 

glycerin,  when  there  is  lack  of  sebaceous  secretions,  790. 

hydrocyanic  acid,  394. 

menthol,  a  useful  local  anaesthetic,  852. 

tobacco,  268. 

validol,  combination  of  menthol  and  valerian,  75. 

Pseudo-membranous  Croup : 

See  CROUP. 
Psoriasis : 

ammonium  iodide,  used  locally  in  form  of  an  ointment,  507. 

aristol,  515. 

arsenic,  employed  internally,  473. 

chrysarobin,  one  of  the  most  efficacious  remedies  known  for  this  disease,  766. 

glycerin,  emollient,  is  excellent  vehicle  for  more  powerful  drugs,  791. 

iodine,  of  secondary  value,  504. 

oil  of  cajuput,  stimulant  and  parasiticide,  629. 

phosphorus,  used  internally,  461. 

pyrogallol,  dangerous  if  used  too  freely,  781. 

resorcin,  855. 

thyroid  extract,  claimed  to  have  a  peculiar  alterative  effect  on  skin,  537. 

Psorophthalmia : 

citrine  ointment,  496. 

Ptyalism  : 

air  opine,  the  most  valuable  internal  remedy  known,  181. 
tannic  acid,  used  in  solution  as  mouth  wash,  404. 

Puerperal  Convulsions : 

amyl  nitrite,  if  used  immediately  after  labor  may  cause  post-partum  hemor- 
rhage, 259. 
anesthetics,  82. 
camphor,  of  little  value,  288. 

chloral,  one  of  the  most  powerful  anticonvulsants  known,  151. 
nitroglycerin,  261. 
See  also  ECLAMPSIA. 

Puerperal  Eclampsia: 

See  ECLAMPSIA. 

Puerperal  Fever: 

digitalis,  as  a  circulatory  stimulant,  328. 

nuclein,  claimed  to  prevent  the  growth  of  septic  bacteria,  531. 


INDEX   OF   DISEASES.  929 

oil  of  turpentine,  may  be  used  both  internally  and  externally,  711. 
streptococcus  antitoxin,  results  have  not  proved  encouraging,  548. 
See  also  SEPTICAEMIA. 

Puerperal  Mania : 

atr  opine,  181. 
splenic  extract,  544. 

Puerperal  Peritonitis : 

mercury,  489. 
Purpura  Haemorrhagica : 

ergot,  probably  not  of  much  value,  752. 

gelatin,  acts  by  increasing  coagulability  of  blood,  533. 

oil  of  turpentine,  711. 

Pysemia : 

alcohol,  as  a  circulatory  and  general  stimulant,  305. 

quinine,  not  probable  that  it  exercises  any  direct  action  on  pyogenic  organ- 
isms, 571. 
tincture  of  ferric  chloride,  450. 

Pyelitis : 

buchu,  a  mild  stimulant  to  the  urinary  mucous  membranes,  705. 

cantharides,  actively  stimulating,  to  be  used  only  in  chronic  cases,  715. 

copaiba,  713. 

juniper,  diuretic  and  stimulating,  used  in  chronic  cases,  707. 

methylene-blue,  doubtful  if  of  value,  581. 

salicylic  acid,  acts  as  urinary  antiseptic,  594. 

turpentine,  712. 

iirotropin,  urinary  antiseptic,  especially  useful  in  lithaemic  patients,  700. 

uva  ursi,  mildly  astringent  and  diuretic,  705. 

Pyogenic  Membranes: 

papain,  818. 
Pyrexia : 

See  FEVER. 
Pyrosis : 

bismiith,  antiseptic  and  sedative,  424. 

manganese  dioxide,  451. 

silver  oxide,  feebly  astringent,  438. 

Q 
Quinsy : 

salicylates,  594. 

R 

Rachitis : 

See  RICKETS.  . 

Remittent  Fever: 

arsenic,  used  only  when  quinine  not  available,  472. 

diaphoretics,  when  paroxysms  are  close  together,  719. 

quinine,  must  be  used  in  full  dose,  5  7.3 . 

Warburg's  tincture,  a  very  powerful  combination  containing  quinine,  579. 

Renal  Calculi: 

atropine,  to  lessen  spasm  during  attacks  of  colic,  180. 
piperazine,  to  prevent  deposition  of  uric  acid,  689. 

Retention  of  Urine: 

strychnine,  when  due  to  atony  of  bladder,  222. 
Retina,  Detachment  of: 

dionine,  144. 

59 


930  INDEX   OF    DISEASES. 

Retinitis  : 

iodipin,  508. 

Retraction  of  Gums: 

iodine,  to  be  applied  locally  with  camel's-hair  brush,  504. 

Rheumatic  Neuralgia : 

aconite,  applied  locally,  383. 

potassium  iodide,  in  subacute  or  chronic  cases,  506. 

salicylates,  the  most  generally  serviceable  remedy,  594. 

Rheumatism : 

aconite,  used  to  produce  sweat,  383. 

ammonium  iodide,  especially  in  chronic  forms,  507. 

avnyl  salicylate,  599. 

arsenic,  in  chronic  cases;  may  be  alternated  with  iodides,  474. 

aspirin,  a  form  of  exhibiting  salicylic  acid  much  less  likely  to  disturb  diges- 
tion, 598. 

Burgundy  pitch,  as  a  mildly  counter-irritant  plaster,  775. 

carbolic  acid  injections,  838. 

cathartics,  653. 

chloroform,  externally  as  counter-irritant,  99. 

cod-liver  oil,  useful  in  chronic  types  especially  when  poor  nutrition,  518. 

colchicum,  in  those  cases  approaching  the  gouty  type,  528. 

diaphoretics,  to  prevent  muscular  rheumatism  following  exposure,  719. 

Donovan's  solution,  used  only  in  chronic  cases,  507. 

Dover's  powder,  as  a  sudorific,  729. 

electricity,  52. 

glycosal,  a  salicylic  preparation  for  external  use,  599. 

gold  and  sodium  chloride,  may  perhaps  be  of  some  service  in  chronic  cases,  498. 

guaiac,  529. 

heat,  local  application  may  relieve  joint,  but  has  no  beneficial  effect  on  general 
condition,  29. 

ichthyol,  mildly  counter-irritant  and  alterative,  528. 

iodine,  used  externally  in  chronic  cases,  510. 

iodoform,  internally  in  chronic  cases  as  analgesic,  510. 

jaborandi,  to  produce  sweating,  726. 

magnesia,  antacid  and  laxative,  656. 

massage,  5. 

meso/an,  a  salicylic  acid  preparation  absorbed  readily  through  the  skin,  599. 

mfthylene-blue,  as  an  analgesic,  581. 

oil  of  cajuput,  629. 

oil  of  gaultheria,  an  active  form  of  salicylate,  598. 

oil  of  peppermint,  externally,  631. 

phenocoll  hydrochloride ,  616. 

phenosol,  618. 

potassium  acetate,  is  antacid  and  increases  oxidation,  especially  valuable  in 
acute  cases,  692. 

potassium  iodide,  a  very  valuable  remedy  in  chronic  cases,  505. 

pyramidon,  in  acute  cases  to  relieve  pain,  618. 

pyrosal,  618. 

quinine,  572. 

rheumatine,  combination  of  salicylic  acid  and  quinine,  579. 

salicin,  inferior  to  salicylates,  599. 

salicylates,  the  standard  remedies  in  all  forms  of  rheumatism,  594. 

salipyrin,  as  an  analgesic,  617. 

salol,  not  very  powerful  but  often  of  service  in  chronic  cases,  847. 

salophen,  acts  much  like  salol,  600. 

sulphur,  as  a  laxative,  also  as  alterative  in  chronic  cases,  657. 

sulphurated  potassa,  658. 

urasol,  a  salicylic  acid  combination,  702. 

xanthoxylum,  530. 

Rheumatism,  Inflammatory : 

antipyrine,  to  relieve  excessive  fever,  607. 

benzoic  acid,  asserted  to  be  equal  to  salicylic  acid,  863. 


INDEX   OF   DISEASES.  931 

cimicifuga,  an  old  remedy  rarely  employed  to-day,  80. 

Dover's  powder,  valuable  on  account  of  diaphoretic  effect,  729. 

lemon-juice,  396. 

oil  of  gaultheria,  597. 

phenocoll  hydrochloride,  616. 

potassium  acetate,  692. 

potassium  nitrate,  inferior  to  vegetable  salts,  694. 

potassium  salts,  one  of  most  valuable  treatments;  encourages  oxidation  and 

corrects  systemic  hyperacidity,  692. 

quinine,  in  very  large  doses,  efficacious  but  dangerous,  572. 
salicylic  acid,  relieves  pain  and  hyperpyrexia  and  probably  has  direct  curative 

effect  on  morbid  metabolism,  594. 
salipyrin,  as  antipyretic,  617. 
veratrine,  dangerous  and  not  effective,  372. 

Rheumatoid  Arthritis: 

arsenic,  probably  the  most  frequently  useful  remedy  known,  474. 

potassium  iodide,  506. 

salicylic  acid,  but  rarely  of  service,  594. 

Rhinitis : 

camphor-menthol,  applied  locally  dissolved  in  liquid  petrolatum,  852. 
hydrastin,  an  excellent  local  remedy  especially  in  chronic  catarrhs,  700. 
ichthargan,  actively  germicidal,  may  be  used  in  spray,  440. 
suprarenal  extract,  constricts  the  engorged  blood-vessels,  542. 
See  also  CATTARRH. 

Rhus-Toxicodendron  Poisoning : 

lobelia,  264. 

Rickets : 

calcium  phosphate,  when  there  is  a  deficiency  of  lime  salts  in  nutriment,  520. 
cod-liver  oil,  a  valuable  remedy  especially  in  poorly  nourished  subjects,  518. 
phosphorus,  stimulates  the  growth  of  bone,  461. 

Rigidity  of  Os  Uteri : 

belladonna,  applied  locally,  180. 
Round- Worms : 

anthelmintics,  805. 

azedarach,  used  but  comparatively  little,  806. 

chenopodium,  a  useful  remedy,  807. 

oil  of  cajuput,  629. 

oil  of  turpentine,  812. 

santonin,  one  of  the  most  active  drugs  against  this  parasite,  809. 

spigelia,  safe  and  efficient,  806. 


Salivation : 

See  PTYALISM. 
Sarcoma : 

streptococcus  toxin,  results  have  been  generally  disappointing,  545. 

Scabies : 

glycerin,  as  an  emollient  vehicle,  790. 
rcsorcin,  somewhat  antiseptic,  855. 
sulphur,  the  most  frequently  employed  remedy,  658. 

Scarlet  Fever: 

aconite,  as  a  febrifuge  in  the  early  stages,  383. 
alcohol,  as  a  circulating  stimulant  for  threatened  collapse,  305. 
ammonia,  rapidly  acting  cardiac  stimulant,  281. 
antipyrine,  to  reduce  hyperpyrexia,  607. 

atropine,  has  no  specific  action,  as  formerly  believed,  but  is  valuable  as  a  stim- 
ulant, 181,  183. 


932  INDEX    OF    DISEASES. 

Scarlet  Fever — Continued: 

capsicum,  as  a  local  application  for  the  accompanying  sore  throat,  629. 
cold,  to  reduce  fever,  37. 

hydrogen  dioxide,  used  as  antiseptic  application  to  the  throat,  829. 
streptococcus  antitoxin,  for  secondary  infections,  especially  of  throat,  548. 
urotropin,  probably  of  use  as  preventive  of  nephritis,  701. 

Sciatica : 

acetopyrin,  as  an  analgesic,  610. 

electricity,  galvanic  current  often  of  great  service  after  acute  inflammation  is 

gone,  57. 
guaiac,  529. 

potassium  iodide,  of  value  in  subacute  rheumatic  cases,  506. 
salicylatcs,  the  most  useful  remedy  in  rheumatic  cases,  594. 
saloquinine,  analgesic  and  antirheumatic,  580. 
sulphur,  used  in  small  doses  as  alterative,  657. 

Scleritis : 

iodipin,  508. 
physostigmine,  237. 

Scleroderma  : 

hiosinamine,  530. 

Scrofulosis : 

alcohol,  as  an  accessory  food,  307. 

ammonium  iodide,  used  both  internally  and  externally  as  a  resolvent,  569. 

calcium  phosphate,  520. 

calx  sulphurata,  internal  remedy  for  scrofulous  glands,  659. 

cod-liver  oil,  to  improve  nutritive  condition,  517. 

gold  and  sodium  chloride,  498. 

gold  oxide,  498. 

ichthalbin,  a  derivative  of  ichthyol  suitable  for  internal  use,  528. 

iodine,  used  internally  for  glandular  enlargements.,  especially  when  no  sup- 
puration, 505. 

phosphoric  acid,  largely  used  but  of  little  value,  519. 

sarsaparilla,  529. 

syrup  of  ferrous  iodide,  combines  alterative  action  of  iodine  with  tonic  effect  of 
iron,  450. 

Scurvy : 

lemon-juice,  a  specific;  the  only  remedy  of  value,  396. 

vinegar,  may  be  substituted  for  lemon  juice,  but  much  inferior,  397. 

Seat- Worms : 

forced  enemata,  650. 

naphtalin,  given  by  injection,  850. 

quassia,  probably  the  most  generally  useful  remedy;  use  in  enema,  622. 

vinegar,  397. 

Seborrhoea : 

arsenic,  internally  when  of  neurotic  origin,  474. 
glycerin,  externally  to  soften  the  skin,  790. 
resorcin,  stimulant  and  antiseptic,  855. 

Seminal  Emissions : 

See  SPERMATORRHCEA 
Septicaemia : 

antitoxin,  has  not  given  brilliant  results,  548. 

cold,  to  reduce  fever,  37. 

colloidal  silver,  its  value  is  problematical,  439. 

formaldehyde,  intravenous  injections  of  no  service,  860. 

ichthargan,  used  hypodermically,  but  no  positive  evidence  of  value,  440. 

quinine,  perhaps  useful  as  antipyretic,  has  no  specific  action,  369. 

Serous  Diarrhoea : 

See  DIARRHOEA. 


INDEX   OF   DISEASES.  933 

Sexual  Excitement: 

camphor,    a   feeble   sedative,    288. 
hops,  frequently  employed  but  of  little  use,  77. 

hyoscine  hydrobromate,  one  of  the  most  reliable  sedatives  known  for  this  con- 
dition, 189. 

monobromated  camphor,  79,  251. 
potassium  bromide,  a  very  valuable  remedy,  246. 
See  also  NYMPHOMANIA. 

Shock : 

See  COLLAPSE. 

Sick  Headache: 

antacids,  to  correct  acidity  of  stomach,  798. 

aromatic  spirit  of  ammonia,  the  most  generally  useful  antacid,  796 

magnesia,  laxative  and  antacid,  656. 

Sick  Stomach : 

creosote,  local  anaesthetic  and  antiseptic,  844. 
ipecacuanha,  as  a  gastric  stimulant  in  atonic  nausea,  637. 

Silver-Nitrate  Poisoning : 

treatment  of,  437. 

Singultus : 

See  HICCOUGH. 

Sinking-Spells : 

See  SYNCOPE. 

Skin  Diseases: 

ammoniated  mercury,  496. 

arsenic,  used  internally  in  chronic  conditions,  473. 

cataplasm  of  kaolin,  793. 

chalk,  as  a  protective  and  desiccant,  803. 

chrysarobin,  an  excellent  stimulating  application,  especially  in  psoriasis,  766. 

citrine  ointment,  496. 

cod-liver  oil,  used  internally  to  improve  nutrition,  518. 

Donovan's  solution,used  internally  as  an  alterative,  507. 

gold  iodide,  498. 

'ichthyol,  a  local  remedy  of  wide  applicability,  527. 

iodine,  occasionally  used  as  an  antiseptic,  504. 

magnesia,  as  a  laxative  antacid,  656. 

naphtol,  as  an  antiseptic  soap,  851. 

nitro-hydrochloric  ac^d,  for  its  stomachic  effect,  456. 

oil  of  cajuput,  stimulating  and  parasiticide,  629. 

ointment  of  zinc  oxide,  428. 

oxide  of  mercury,  496. 

phosphorus,   internally  in  various  chronic  conditions,  461. 

sulphur,  used  both  internally  and  externally,  657. 

sulphurated  potassa,  658. 

tar,  737. 

thyroid  extract,  especially  in  psoriasis  and  keloid,  537. 

vinegar,  as  a  sedative  astringent  in  acute  inflammations,  397. 

zinc  oxide,  a  widely  useful  astringent,  427. 

Sleeplessness : 

amylene  hydrate,  163. 

bromipin,  a  preparation  of  bromides,  251. 

bromolein,  251. 

cannabis  indica,  195. 

chloral,  the  most  powerful  hypnotic  known  in  nervous  insomnia,  150. 

chloralformamid,  less  powerful  but  less  depressant  than  chloral,   165. 

chloralase,  uncertain  in  its  effects,  165. 

chloretone,  feeble  but  safe,  162. 

dormiol,  of  moderate  power  in  insomnia  of  nervous  origin,  163. 


934  INDEX    OF   DISEASES. 

Sleeplessness —  Continued. 

hedonal,  sometimes  of  use  in  cases  of  not  great  severity  nor  associated  with 
pain,  163. 

hyoscide  hydrobromide,  especially  serviceable  in  insomnia  of  insanity  or  de- 
lirium, 189. 

hypnone,  164. 

isopral,  164. 

lactic  acid,  feeble  and  uncertain,  457. 

methylal,  163. 

opium,  chiefly  of  value  in  insomnia  due  to  pain,  133. 

paraldehyde,  a  safe  and  powerful  remedy  in  sleeplessness  not  associated  with 
pain,  161. 

potassium  bromide,  comparatively  feeble  as  direct  somnifacient,  but  useful  in 
cases  where  wakefulness  is  caused  by  stimuli  from  without,  245. 

sulphonal,  a  slowly  acting  but  fairly  powerful  remedy,  156. 

trional,  less  likely  to  cause  chronic  poisoning  than  sulphonal,  160. 

urethan,  a  safe  and  moderately  active  remedy  in  nervous  insomnia,  163. 

veronal,    164, 

Smallpox : 

ichthyol,  employed  locally  to  prevent  pitting,  527. 
opium,  to  sustain  system  by  blunting  sensibilities,  134. 
thiosinamine ,  to  cure  the  scars  after  smallpox,  530. 

Snake- Poisoning : 

alcohol,  of  value  as  circulatory  stimulant,  but  is  not   a  specific  as  sometimes 

believed,  306. 

ammonia,  a  useful  heart  stimulant,  inject  hypodermically,  281. 
antitoxin,  acts  specifically  in  bites  from  certain  varieties  of  snakes,  550. 
potassium  permanganate,  as  a  local  antidote;  should  be  injected  into  wound, 

827. 

Sore  Nipples : 

See  NIPPLES,  SORE. 

Sore  Throat: 

acacia,  dissolved  in  the  mouth  is  very  soothing  in  acute  inflammations,  782. 

alum,  as  an  astringent,  not  fitted  for  gargle,  410. 

atr  opine,  181. 

carbolic  acid,  in  ulcerated  or  diphtheritic  sore  throat  as  an  antiseptic,  837. 

chlorine  water,  as  a  disinfectant  gargle  in  violent  infections,  826. 

cocaine,  applied  locally  as  vasoconstrictor  and  anaesthetic,  207. 

creosote,  locally  as  antiseptic,  844. 

gum  arabic,  a  demulcent,  used  in  high-grade  irritations,  782. 

mercury,  internally  as  antiphlogistic,  489. 

phenol  injections,  838. 

potassium  chlorate,  a  very  valuable  astringent  in  not  too  acute  inflammations, 

697. 

salicylates,  specifics  in  tonsillitis  and  rheumatic  angina,  594. 
silver  nitrate,  sedative  astringent  and  germicidal,  435. 
sumach  berries,  make  an  excellent  astringent  gargle,  409. 
tannic  acid,  applied  by  swab  or  as  a  gargle,  404. 

Spasms : 

aconite,  not  generally  useful,  383. 

amyl  nitrite,  a  very  powerful  and  rapidly  acting  but  fugacious  relaxant,  259. 

anaesthetics,  in  severe  hysterical  or  spinal  convulsions,  81. 

asafetida,  when  due  to  hysteria,  76. 

atr  opine,  in  local  spasms  especially  of  involuntary  muscles,  180. 

chloral,  in  all  forms  of  violent  generalized  convulsions  a  valuable  remedy,  152. 

ether,  91. 

hyoscine,  in  asthma,  whooping-cough,  and  similar  disorders,  189. 

lobelia,  in  spasms  of  the  bronchial  muscles,  264. 

oil  of  cajuput,  recommended  in  intestinal  spasms,  629. 

opium,  especially  in  cerebral  or  painful  spasms,  133. 


INDEX   OF    DISEASES.  935 

potassium  bromide,  one  of  the  most  valuable  remedies  in  spinal  and  epileptic 

convulsion,  246. 
sulphonal,  a  feeble  anticonvulsant,   137, 

Spermatorrhoea : 

antipyrine,  608. 

chloral,  useful  in  spasmodic  types,  152. 

digitalis,  asserted  to  be  actively  anaphrodisiac,  328. 

kyoscine  hydrobromide,  one  of  the  most  valuable  remedies  known,  189. 

monobromated  camphor,  251. 

potassium  bromide,  a  very  useful  sexual  sedative,  240. 

sulphonal,  157. 

turpentine,  in  cases  with  marked  atony,  712. 

Spinal  Congestion : 

ergot,  753. 

Spinal  Depression : 

strychnine,  220. 

Spinal  Scleroses : 

gold  and  sodium  chloride,  beneficial  results  have  been  claimed  for  it,  498. 
silver  nitrate,  an  old  remedy  of  doubtful  value,  436. 

Spleen,  Enlargement  of: 

cold,  douche  said  to  be  of  service  in  post-malarial  or  even  leukaemic  spleens,  32. 
ergot,  contracts  vessels,  useful  in  cases  of  chronic  congestion,  752. 
potassium  bromide,  in  post-malarial  spleens,  246. 

Spongy  Gums : 

tannic  acid,  404. 
Sprains : 

arnica,  as  a  stimulant  application,  373. 

camphor,  as  a  counter-irritant,  288. 

dilute  acetic  acid,  a  sedative,  astringent  lotion,  397. 

heat,  locally  applied  of  great  service  after  acute  inflammation  has  subsided,  29. 

ichthyol,  528. 

lead  water,  a  frequently  employed  sedative  embrocation,  422. 

massage,  to  be  used  after  acute  stage  has  subsided,  5. 

vinegar,  397. 

Status  Epilepticus: 

amyl  nitrite,  258. 
Stomatitis : 

boric  acid,  a  large  crystal  of  borax  allowed  to  dissolve  in  the  mouth  is  an  excel- 
lent treatment,  869. 

phenol,  the  ulcers  to  be  touched  with  a  concentrated  solution  in  glycerin,  837. 
potassium  chlorate,  employed  both  as  a  mouth  wash  and  taken  internally,  697. 
sodium  chlorate,  (note)  695. 

Strangury : 

ftaxseed,  popularly  used  in  form  of  a  decoction,  784. 
opium,  best  administered  per  rectum,  140. 

Stricture : 

anaesthetics,  in  spasmodic  stricture  of  oesophagus,  86. 

belladonna,  in  spasmodic  stricture  of  either  urethra  or  bowels,  180. 

thiosinamine ,  asserted  to  be  useful  in  true  urethral  stricture,  530. 

Strychnine-Poisoning : 

amyl  nitrite,  use  by  inhalation  or  hypodermically  to  produce  immediate  re- 
laxation, 259. 

chloral,  a  very  useful  spinal  depressant,  151. 
physiological  salt  solution,  to  aid  in  elimination  of  poison,  679. 
physostigma,  a  remedy  of  only  secondary  power,  237. 
potassium  bromide,  a  valuable  physiological  antagonist,  246. 
treatment  of,  225. 


936  INDEX    OF    DISEASES. 

Subinvolution  of  Uterus: 

ergot,  754. 

Suffocative  Catarrh: 

apomorphine  hydrochlorate,  as  an  emetic  to  evacuate  exudate,  642. 
garlic,  used  externally  in  form  of  poultices,  737. 
treatment  of  asphyxia  in,  729. 

Sulphonal-Poisoning : 

treatment  of,  158. 
Summer  Complaint: 

See  CHOLERA  INFANTUM 

Sunburn : 

dilute  acetic  acid,  a  valuable  sedative  astringent,  397. 
vinegar,  397. 

Suppressed  Menstruation : 

See  AMENORRHCEA. 

Suppression  of  Urine : 

calomel,  one    of    the    most    powerful    diuretics    known    in    parenchymatous 

nephritis,  683. 
digitalis,  in  acute  suppression  a  poultice  of  the  leaves  may  be  applied    over 

loins,  686. 

jaborandi,  given  in  small  doses  sometimes  of  service,  726. 
water,  when  suppression  dependent  on  acute  irritation  of  kidneys,  678. 

Sweating,  Excessive : 

See  HYPERIDROSIS. 

Syncope : 

alcohol,  a  rapidly  acting  cardiac  stimulant,  304. 

ammonia,  irritant  action  of  vapors  on  mucous  membrane  of  nose  acts  reflexly 

as  stimulant,  281. 

amyl  nitrite,  a  dangerous  remedy,  as  the  slightest  overdose  is  depressant,  258. 
digitalis,  give  hypodermically  in  large  doses,  326. 
ether,  91. 

Synovitis : 

carbolic  acid,  injections,  838. 

heat,  applied  locally  especially  in  chronic  cases,  29. 

Syphilis : 

ammonium  iodide,  used  either  internally  or  externally  as  a  resolvent,  507. 

aristol,  as  a  dusting  powder  for  ulcers,  515. 

berberis,  624. 

calcium  phosphate,  recommended  in  syphilitic  periostitis,  also  in  gumma,  520. 

cod-liver  oil,  in  the  cachexia  of  tertiary  stage,  518. 

gold  and  sodium  chloride,  in  sclerosis  of  nervous  system,  498. 

gold  iodide,  498. 

guaiac,  a  remedy  of  secondary  importance,  may  be  used  as  adjunct,  529. 

ichthaWin,  528. 

iodipin,  has  same  effect  as  iodides,  but  acts  more  slowly  and  persistently,  508. 

iodoform,  used  internally  especially  when  "night-pains,  '510. 

iodol,  514. 

mercury,  especially  useful  in  early  stages,  but  a  specific  in  all  forms,  489. 

nitric  acid,  455. 

nitro-hydrochloric  acid,  to  improve  digestion,  456. 

oxide  of  gold,  498. 

potassium  iodide,  a  specific,  employed  most  frequently  in  tertiary  stage,  506. 

red  mercuric  iodide,  a  valuable  form  of  mercurial,  496. 

sarsaparilla,  perhaps  of  service  as  adjunct,   528. 

sulphur,  natural  sulphur-waters,  recommended  in  chronic  syphilis,  658. 

thiosinamine,  as  a  local  application  in  syphilitic  skin  lesions,  530. 

yellow  mcrcurous  iodide,  a  very  efficient  mercurial,  495. 


INDEX   OF   DISEASES.  937 

T 
Tabes  Mesenterica : 

cod-liver  oil,  increases  general  nutrition,  517. 
Tapeworm : 

anthelmintics,  805. 

aspidium,  one  of  the  best  remedies  against  tapeworm,  but  is  poisonous,  812. 

chloroform,  probably  of  little  value,  99. 

cusso,  efficient  and  harmless,  807. 

ether,  of  only  secondary  value,  91. 

forced  enemata,  650. 

kamala,  813. 

oil  of  wormseed,  rarely  used,  807. 

pepo,  the  safest  and  one  of  the  most  powerful  taenicides,  812. 

pomegranate,  efficient,  but  poisonous  in  overdose,  813. 

thymol,  8 1 1 . 

turpentine,  812. 

Tetanus : 

amyl  nitrite,  to  allay  spasm  which  threatens  immediate  death,  although  power- 
ful too  fugacious  for  constant  use,  259. 

antipyrine,  608. 

antitoxin,  is  of  service  in  more  chronic  cases,  547. 

cannabis  indica,  195. 

chloral,  one  of  the  most  generally  serviceable  remedies  known,  151. 

phenol,  hypodermic  injections  have  been  asserted  to  act  very  favorably,  837. 

physostigma,  useful  as  adjunct,  too  feeble  to  be  relied  upon,  236. 

potassium  bromide,  probably  the  best  single  remedy,  must  be  used  in  large 
doses,  246. 

urethane,  163. 

Tic  Douloureux: 

croton  chloral,  1 66. 
gelsemium,  267. 

Tinea  Capitis : 

acctozone,  as  a  local  germicide,  830. 

lime-water,  valuable  as  a  sedative  application,   802. 

resorcin,  stimulant  and  parasiticide,  855. 

Toadstool-Poisoning : 

atropine,  182. 

Tonsillitis : 

capsicum,  applied  locally  with  a  swab,  629. 
gnaiac,  used  internally,  529. 
ichthargan,  as  a  local  germicidal  astringent,  440. 
See  also  SORE  THROAT. 

Toothache : 

oil  of  cloves,  saturated  pledget  of  cotton  placed  in  cavity,  626. 

Torticollis : 

atropine,  injected  deeply  into  muscle,  180. 
hyoscine,  usually  fails,   189. 

Trachoma : 

ichthargan,  440. 
Trichiniasis : 

picric  acid,  814. 
Trismus  Nascentium : 

Calabar  bean,  236. 
chloral,  151. 
physostigma,  236. 


938  INDEX   OF    DISEASES. 

Tuberculosis : 

arsenic,  as  a  reconstructive  alterative  especially  in  chronic  cases,  474. 
arsenic  iodide,  as  a  local  application  in  external  tuberculosis,  482. 
cacodylic  acid,  a  mode  of  exhibiting  arsenic,  482. 
camphoric  acid,  for  the  relief  of  night  sweats,  288. 
cantharidin,  (note)  771. 

cinnamic  acid,  in  pulmonary  tuberculosis  probably  useful  as  a  stimulating  ex- 
pectorant, 864. 

cod-liver  oil,  one  of  the  most  valuable  drugs  known  to  improve  nutrition,  517. 
colloidal  silver,  439. 

fuaiacol,  as  a  stimulant  expectorant,  846. 
eroine,  to  allay  cough  in  phthisis,  145. 

iodoform,  as  a  local  application  especially  in  joint  tuberculosis,  512. 
lecithin,  asserted  to  exercise  a  beneficial  effect  on  nutrition,  552. 
nucleins,  531. 

pyramidon,  to  reduce  excessive  fever,  618. 
tannoform,  as  an  antiseptic  astringent  in  diarrhoea,  405. 
See  also  PHTHISIS. 

Tympanites : 

aromatic s,  625. 

asafetida,  especially  valuable  in  debilitated  subjects,  75. 

escharotics,  776. 

physostigma,  a  direct  stimulant  to  intestinal  muscle  fibres,  237 

Typhoid  Fever: 

For  methods  of  controlling  temperature  see  under  FEVER. 

For  treatment  of  hemorrhage  see  under  HEMORRHAGE  FROM  THE  BOWELS. 

acetozone,  as  an  intestinal  antiseptic,  830. 

alcohol,  an  essential  part  of  the  treatment;  aids  digestion,  acts  as  food,  and 

stimulates  circulation,  307. 

beta-naphtol,  lessens  intestinal  fermentation  by  its  antiseptic  effects,  851. 
caffeine,  347. 
camphor,  hypodermically  in  threatening  collapse,  a  powerful  heart  stimulant, 

287. 

cold,  best  means  of  combating  hyperpyrexja,  37. 
creosote,  as  intestinal  antiseptic,  844. 

digitalis,  claimed  to  act  as  antipyretic  as  well  as  cardiac  stimulant,  328. 
guaiacol,  as  an  antipyretic  is  dangerous,  846. 
hydrochloric  acid,  of  little  benefit,  454. 
jaborandi,  726. 

musk,  in  conditions  with  low  muttering  delirium  a  very  valuable  remedy,  74. 
naphtalin,  850. 
oil  of  turpentine,  best  remedy  for  tympanites,  acts  as  an  intestinal  antiseptic 

and  carminative,  711. 

salol,  probably  most  effective  intestinal  antiseptic,  845. 
sulphur,  656. 

suprarenal  extract,  to  check  hemorrhage  from  bowels,  542. 
thymol,  of  little  value,  853. 

Typhus  Fever: 

alcohol,  useful  as  an  accessory  food  as  well  as  circulatory  stimulant,  305. 

antipyrine,  to  reduce  excessive  pyrexia,   607. 

ati -opine,  as  a  circulatory  stimulant,  181. 

chloral,  as  a  cerebral  sedative  in  delirious  cases,  150. 

chlorine  water,  826. 

cold,  to  control  fever,  37. 

U 
Ulcer  of  Cornea: 

See  CORNEAL  ULCER. 

liberation  of  the  Bowels : 

copper  sulphate,  429. 
oil  of  turpentine,  711. 


INDEX   OF   DISEASES.  939 

Ulcers : 

acetozone,  830. 

alum,  astringent,  used  when  excessive  secretions,  411. 

aluminum  sulphate,  411. 

black  wash,  in  syphilitic  ulcers,  496. 

Canquoin's  paste,  as  a  caustic  in  syphilitic  growths,  779. 

chalk,  as  a  desiccant  and  protective,  803. 

chloral,  anaesthetic  and  antiseptic,  152. 

chloretone,  somewhat  antiseptic  and  locally  anaesthetic,  162. 

chlorine  water,  a  stimulant  disinfectant  application,  826. 

cold  douclie,  as  a  stimulant  to  sluggish  ulcers,  31. 

copaiba,  in  chronic  ulcers  of  the  stomach,  711. 

copper  sulphate,  in  \ndolent  ulcers  especially  of  mucous  membranes,  429. 

creosote,  as  a  disinfectant  in  foul  ulcers,  844. 

eschar otics,  to  destroy  exuberant  granulations,  776. 

ichthargan,  a  silver  germicidal  preparation,  440. 

ichthyol,  527. 

iodoform,  a  desiccant,  alterative,  and  antiseptic,  511. 

lead  plaster,  as  a  protective  in  superficial  ulcers,  421. 

lime-water,  803. 

mezereon,  529. 

nitric  acid,  actively  caustic,  780. 

phenol,  an  active  germicide,  837. 

potassium  permanganate,  antiseptic  and  cleansing,  used  where  much  suppu- 
ration, 827. 

red  mercuric  oxide. 

resin  cerate,  a  stimulant  application,  708. 

silver  nitrate,  mildly  stimulant  and  actively  germicidal,  used  especially  to 
destroy  exuberant  granulations,  435. 

solution  of  mercuric  nitrate,  as  a  caustic,  779. 

sulphuric  acid,  a  dilute  solution  stimulant  and  astringent,  452. 

tannic  acid,  to  lessen  excessive  secretion  on  old  ulcers,  404. 

tannoform,  supposed  to  be  both  antiseptic  and  astringent,  406. 

thyroid  extract,   538. 

yellow  wash,  in  syphilitic  ulcers,  496. 

zinc  oxide,  used  as  desiccant  and  astringent  dusting  powder,  427. 

zinc  sulphate,  781. 

Uncinariasis : 

thymol,  813. 
Unilateral  Sweating: 

jaborandi,   726. 
Uraemia : 

chloral,  to  control  convulsions,  151. 

elaterin,   a   hydragogue   purgative   believed   to   eliminate   urea  through  the 

bowels,  674. 

jaborandi,  as  a  diaphoretic,  726. 
nitroglycerin,  used  to  overcome  spasms,  261. 
opium,  used  as  anticonvulsant  and  diaphoretic,  but  dangerous  on  account  of 

effect  on  secretion  of  urine,  135. 
quebracho,  to  combat  dyspnoea,  278. 

Urethral  Fever: 

aconite,   383. 

potassium  bromide,  lessens  irritability  of  genital  system,  246. 

Urethral  Spasm : 

belladonna,  180. 

Urethritis : 

acetanilid,  a  suspension  may  be  used  locally,  614. 

copper  sulphate,  429. 

silver  nitrate,  actively  astringent  and  germicidal,  435. 

terebene,  used  internally  in  later  stages,  738. 

See  also  GONORRHOEA. 


940  INDEX    OF    DISEASES. 

Uric  Acid  Calculus  and  Gravel : 

bcnzoic  acid,  one  of  the  most  generally  useful  remedies  known,  863. 

piper azine,  useful  in  gravel,  699. 

potassium  salts,  of  service  as  prophylactic,  693. 

quinic  acid,  claimed  to  greatly  lessen  output  of  uric  acid,  701. 

quinotr opine,  701. 

sidonal,  a  combination  of  piperazine  and  quinic  acid,  701. 

soda,  inferior  to  potash,  800. 

Uric  Acid  Diathesis: 

benzoic  acid,  a  useful  remedy,  863. 
lithium,  much  employed  but  of  uncertain  value,  698. 
lycetol,  699. 

potassium  salts,  increase  oxidative  processes  of  body,  frequently  of  much  ser- 
vice,  693. 
sodium,    800. 

sodium  phosphate,  as  a  laxative,  669. 
treatment  of,  24. 

Urticaria : 

arsenic,  in  chronic  forms,  473. 

cimicifuga,  acts  almost  specifically  in  neurotic  cases,  78. 

emetics,  when  due  to  gastric  irritation,  633. 

ichthyol,  as  a  local  application,  527. 

menthol,  as  a  local  application  to  lessen  itching,  852. 

Uterine  Inertia: 

ergot,  to  be  used  very  cautiously  on  account  of  danger  of  uterine  spasm,  750. 
quinine,  in  full  dose  sometimes  of  service,  568. 

Uterus,  Cancer  of : 

chloral,  as  a  local  anaesthetic  and  antiseptic,  152. 
cotton  root,  to  arrest  the  hemorrhage,  764. 
iodoform,  applied  locally  to  allay  pain,  513. 

Uterus,  Fibroid  Tumors  of : 

cotton-root,  to  allay  hemorrhage  or  other  symptoms,  764. 
ergotin,  has  been  administered  hypodermically,  753. 
mammary  gland,  53 1 . 

Uterus,  Subinvolution  of: 

ergot,    754- 
Uveitis : 

dionine,  increases  lymphatic  circulation  in  eye,  144. 
salicylic  acid,  594. 


Vaginismus  : 

piper  in,   628. 
Vaginitis : 

acetanilid,  used  locally  in  a  suspension,  stimulant  antiseptic,  614. 

bismuth  oxyiodogallate ,  used  in  suppository,  antiseptic  and  sedative,  426. 

erindelia,  736. 

hydrastin,  influences  mucous  membrane  directly,  760. 

ichthargan,  a  germicidal  silver  preparation,  440. 

Valvular  Heart  Disease : 

See  ENDOCARDITIS. 
Varicose  Veins  : 

ergot,  used  locally,  but  probably  of  little  value,  752. 
hamamelis,  feebly  astringent,  408. 

Venereal  Ulcers : 

See  CHANCRES  AND  CHANCROIDS. 


INDEX   OF    DISEASES.  941 

Venereal  Warts : 

nitric  acid,  454. 

Veratrum- Viride  Poisoning : 

alcohol,  as  a  heart  stimulant,  306. 
treatment  of,  369. 

Vesical  Tenesmus : 

ancesthesin,  118. 

Vomiting : 

aconite,  locally  stimulant  and  anaesthetic,  especially  valuable  in  pregnancy,  383. 

ancesthesin,  acts  as  a  local  anaesthetic,  118. 

bismuth  subnitrate,  sedative,  astringent,  and  antiseptic,   424. 

cerium  oxalate,  believed  to  have  a  specific  action  especially  in  vomiting  of 

pregnancy,  427. 
chloretone,  162. 

cocaine,   paralyzes  the  sensory  nerves  of  stomach,   207 
creosote,  antiseptic  and  local  anaesthetic,  844. 
hydrastin,  stomachic,  760. 

ipecacuanha,  in  atonic  conditions  especially  in  pregnancy,  637. 
lime  water,  to  render  milk  more  easily  digested,  802. 
opium,  one  of  the  best  remedies  we  have,  benumbs  vomiting  centre;  may  be 

given  per  rectum,  134,  140. 
orexin,  stimulant  to  gastric  mucosa,  especially  recommended  after  anaesthesia 

and  in  pregnancy,  625. 

phenol,  antiseptic  and  locally  anaesthetic,  often  of  great  service  in  gastritis,  837. 
potassium  bromide,  in  reflex  vomiting  from  uterine  disturbances,  .246. 
prussic  acid,  local  anaesthetic,  391. 
treatment  of,  634. 
valyl,  in  hysterical  conditions,  77. 

W 

Warts: 

nitric  acid,  one  of  the  most  generally  useful  caustics,  454. 

pa  fain,  supposed  to  dissolve  them  by  a  process  similar  to  digestion,  8r8. 

White  Swelling : 

See  JOINTS,    INFLAMMATION  OF. 

Whooping-Cough  : 

antipyrine,  of  some  value  as  antispasmodic,  607. 

aristochin,  a  synthetic  quinine  derivative,  579. 

arsenic,  476. 

asafetida,   antispasmodic  and  expectorant,    76. 

atropine,  a  valuable  remedy  on  account  of  antispasmodic  action,  180 

bromoform,  doubtful  if  it  possesses  any  virtue  not  found  in  bromides,  250. 

camphor,  its  use  has  largely  passed  out  of  vogue,  288. 

chloral,  useful  temporarily  to  check  spasms,  152. 

conium,  an  unreliable  remedy,  272. 

euquinine,  probably  less  efficient  than  quinine,  579. 

gelsemium,  267. 

grindelia,  as  an  expectorant,  736. 

heroine,  as  a  cough  sedative,  145 

hyoscine,  for  its  antispasmodic  effect,  185. 

quinine,  seems  to  act  specifically,  perhaps  exercises  antiseptic  effect,  575. 

thermal,  acts  like  phenacetin,  618. 

thyme,  853. 

Winter  Cough : 

See  BRONCHITIS. 
Worms : 

See  ROUND-WORMS  and  TAPEWORMS. 


942  INDEX   OF   DISEASES. 

Wounds : 

acetanilid,  as  antiseptic  dusting  powder,  of  secondary  value,  614. 

alcohol,  actively  antiseptic  and  sedative,  especially  used  as  a  dressing,  309. 

aristol,  a  useful  desiccant  and  antiseptic  dusting  powder,  515. 

bismuth  subgallate,  as  a  dusting  powder,  427. 

boric  acid,  feebly  antiseptic,  869. 

chloretone,  locally  anaesthetic  and  somewhat  antiseptic,   162. 

escharotics,  in  poisoned  wounds,  as  bites,  or  when  seriously  infected,  776. 

formaldehyde,  powerfully  disinfectant  but  too  irritant  for  ordinary  uses,  of 

service  when  severe  infection,  859. 

hydrogen  dioxide,  cleansing  on  account  of  its  oxidizant  action,  also  antiseptic. 
iodoform,  desiccant,  anaesthetic  and  slightly  antiseptic,  511. 
orthoform,  useful  in  painful  wounds,  local  anaesthetic,  and  somewhat  antiseptic, 

118. 

phenol,  actively  bactericidal,  837. 

potassium  permanganate,  oxidizant  and  disinfectant,  827. 
protargol,  a  germicidal  silver  preparation,  441. 
quinine,  (note)  575. 

Y 

Yellow  Fever: 

antipyrine,  to  control  hyperpyrexia,  607. 


GENERAL  INDEX. 


Abies  balsamea,  708 

excelsa,  775 
A.  B.  S.  pill,  666 
Absolute  acetic  acid,  397 

alcohol,  289 
Absorbent  cotton,  764 
Absorbents,  819 
Acacia,  782 

catechu,  407 

Senegal,  782 

A.  C.  E.  mixture,  (note)  106 
Aceta,  61 
Acetanilid,  610 
Acetanilidum,  610 
Acetic  acid,  397 

ether,  79 

poisoning,  397 
Acetonchloroform,  162 
Acetone,  397 
Acetonum,  (note)  397 
Acetophenone,  164 
Acetopyrin,  610 
Acetozone,  830 
Acetphenetidin,  614 
Acetphenetidinum,  614 
Acetum,  396 

opii,  141 

scillae,  682 
Acetyl-methylene-disali- 

cylic  acid,  702 
Acetylparamidophenyl,  599 
Acetyl-salicylic  acid,  598 
Acetyl-salicyl-phenetidin, 

'  618 

Acid  potassium  pxalate,  398 
Acids  and  alkalies,  864 
Acidum  aceticum,  397 

aceticum  dilutum,  397 

aceticum  glaciale,  397 

benzoicum,  861 

boricum,  866 

camphoricum,  288 

carbolicum  crudum,83i 

cinnamicum,  864 

citricum,  395 

gal  lieu  m,  406 

hydriodicum    dilutum, 
508 

hydrobromicum     dilu- 
tum, 249 

hydrochloricum,  454 

hydrochloricum     dilu- 
tum, 454 


Acidum  hydrocyanicum, 

385 

hydrocyanicum     dilu- 
tum, 385,  393 
hypophosphorosum , 

520 

lacticum,  457 
nitricum,  454,  780 
nitricum  dilutum,  455 
nitro-hydrochloricum, 

455 
nitrp-hydrochloricum 

dilutum,  455 
nitrosum,  455 
oleicum,  787 
oxalicum,  397 
phosphoricum,  518 
phosphoricum  dilutum, 

5i8 

picrum,  814 
quinicum,  701 
salicylicum,  587 
stearicum,  788 
sulphuricum,  453 
sulphuricum     aromati- 

cum,  454 
sulphuricum    dilutum, 

454 

sulphurosum,  864 
tannicum,  402 
tartaricum,  394 
trichloraceticum,  780 

Aconine,  374,  (note)  380 

Aconite,  373 

poisoning  by,  383 

Aconitine,  374,  385 

Aconitum,  373 

anthora,  (note)  374 
cammarum,  (note)  373 
ferox,  (note)  373 
fischeri,  (note)  374 
japonicum,  (note)  374 
lycoctonum,  (note)  374 
napellus,  373 
neomontanum,    (note) 

373  , 
pamculatum,       (note) 

37.3 

tauncum,  (note)  373 

variabile,  (note)  373 
Acrinyl  sulphocyanate,  773 
Actol,  438 
Adeps,  786 

benzoinatus,  786,  863 

lanae,  788 


Adeps  lanae  hydrosus,  788 
Adhesive  plaster,  421,  708, 

796 

Adjuvant  elixir,  784 
Adonidin,  354 
Adonis  vernalis,  354 
Adrenalin,  539 
Adrenals,  538 
yEther,  87 

aceticus,  79 
^Ethylis  chloridum,  100 

carbamas,  163 
^thyl-sulphonic  acid,  155 
African  arrow-poison,  312 

pepper,  628 
Agaric,  409 

acid,  409 
Agaricin,  409 
Agaricinic  acid,  409 
Age  in  relation  to  dose,  66 
Agropyrin  repens,  706 
Airol,  426 
Albargin,  438 
Alcohol,  289 

absolutum,  289 

dilutum,  289 

poisoning,  310 
Alexandria  senna,  666 
Alimentation,  rectal,  14 
Allis  inhaler,  in 
Allium,  736 

sativum,  736 
Allspice,  627 
Allyl-sulphocarbamide, 

529 

sulpho-urea,  529 
A*loe,  664 

purificata,  665 
Aloes,  664 

Barbadoes,  664 

Cape,  664 

Socotrine,  664 
Aloin,  664 
Aloinum,  664 
Alpha-eucaine,  117 
Alterative  diuretics,  704 
Alteratives,  459 
Althaea,  785 

officinalis,  785 
Alum,  410 

curd,  411 

dried,  410 

poisoning,  410 
Alumen,  410 

exsiccatum,  410 

943 


944 


GENERAL    INDEX. 


Aluminii  hydroxidum,  411 

sulphas,  411 
Aluminum  hydrate,  411 

hydroxide,  411 

sulphate,  411 
Alypin,  118 

American  silver  fir,  706,  708 
Amido-camphor,  (note)  283 
Ammonia,  279,  774 

alum,  410 

poisoning,  282 

water,  282 
Ammoniac,  739 

emulsion,  739 

plaster  with   mercury, 

Ammoniacum,  739 
Ammoniated  mercury,  496 

tincture  of  guaiac,  529 

tincture  of  valerian,  75 
Ammonii  benzoas,  864 

bromidum,  247 

carbonas,  282 

chlpridum,  734 

iodidum,  507 

nitras,  283 

salicylas,  596 

valeras,  75 

Ammonium  acetate,    solu- 
tion of,  728 

benzoate,  864 

bromide,  247 

carbonate,  282 

cathartate,  666 

chloride,  734 

ichthyo-sulphate,  527 

iodide,  507 

nitrate,  283 

picrate,  814 

sal  icy  late,  596 

valerate,  75 

valerianate,  75 
Amorphous  aconitine,  374 

aspidospermine,  277 
Ampere,  45 
Amygdala  amara,  394 
Amygdalin,  624 
Amylene  chloral,  163 

hydrate,  163 
Amyl  nitrite,  252 
Amylis  nitris,  252 

salicylas,  599 
Amylum,  784 
Anaesthesia,  practical,  103 

accidents  in,  112 

after-effects  of,  116 

local,  117 
Anaesthesin,  118 
Anesthetics,  81 
Anarcotine,  142 
Anclira  araroba,  766 
Animal  charcoal,  819 

drugs,  530 
Anise,  630 
Anisum,  630 
Annidaline,  514 


Antacids,  797 
Anthelmintics,  805 
Anthem  is,  631 

nobilis,  631 

Anthracene,  (note)  663 
Anthrarobin,  (note)  766 
Antidiphtheric  serum,  545 
Antifebrin,  610 
Antimonial  ointment,  366 

wine,  366 

Antimonii  et  potassii   tar- 
tras,  360 

oxidum,  360 

sulphidum,  360 

purificatum,  360 
Antimonium  sulphuratum, 

360 
Antimony,  360 

and  potassium  tartrate, 
360 

oxide,  360 

poisoning  by,  304 

sulphide,  360 
Antinosine,  515 
Antiperiodics,  555 
Antipyretics,  586 
Antipyrin,  600 

aceto-salicylate,  617 

salicyl-acetate,  618 

salicylate,  617 
Antipyrina,  600 
Antipyrylurea,  617 
Antiseptics,  820 
Antispasmodics,  73 
Antitoxins,  544 
Antitussin,  865 
Antivenin,  550 
Apiol,  743 

Apium  petroselinum,  743 
Apocodeine,  651 
Apocynein,  333 
Apocynin,  333 
Apocynum,  333 

cannabinum,  333 
Apomorphinae    hydrochlo- 

ras,  639 
Apomorphine,  639 

hydrochlorate,  639,  734 
Apothecaries'  measure,  879 

weights,  879 

Apparatus  for  artificial  res- 
piration, 114 
Appendix,  879 
Aqua  ammoniaa,  282,  774 

ammoniac  fortior,  282, 

774  .. 

aurantu  florum,  630 
camphorae,  288 
chloroformi,  100 
cinnamomi,  626 
creosoti,  845 
foeniculi,  630 
hamamelis,  408 
hydrogenii  dioxidi,  828 
menthae  piperitae,  630 
menthae  viridis,  630 


Aqua  rosce,  409 

Aquae,  61 

Arabin,  782 

Araroba,  766 

Arbutin,  705 

Arctostaphylos     uva     ursi, 

7t>5 

Argel-leaves,  666 
Argenti  acetas,  438 

casein,  439 

citricum  438 

cyanidum,  394,  438 

lactas,  438 

nitras,  431,  822 

nitras  dilutus,  438 

nitras  fusus,  431 

oxidum,  438 

sulphophenas,  439 
Argentol,  438 
Argentum,  431 

solubile,  439 
Argol,  395 
Argonin,  439 
Argyria,  432 
Argyrol,  438 
Aristochin,  579 
Aristol,  514 
Aristolochia  reticulata,  631 

serpentaria,  631 
Arnica,  372 

montana,  372 

root,  372 
Arnicine,  372 
Aromatic  bitters,  631 

fluid  extract,  626 

fluid  extract  of  cascara 
sagrada,  655 

powder,  626 

spirit  of  ammonia,  282 

spirit  of  hartshorn,  282, 


798 
sulp 


phuric  acid,  454 

syrup  of  rhubarb,  664 

tincture  of  rhubarb,  664 
Aromatics,  625 
Arrow-poison,  334 
Arrow-root  porridge,  1 2 
Arseni  iodidum,  482 
Arsenic,  468 

antidotes,  480 

as  a  caustic,  778 

-eating,  472 

iodide,  482 

poisoning,  acute,  474 
chronic,  478 

post-mortem    imbibi- 
tion, 481 

trioxide,  468 
Arsenical  paper,  com- 
pound, 732 

solution  of  lithium,  698 
Arsenii  trioxidum,  468 
Arsenous  acid,  468 
Art  of    prescribing    medi- 
cines, 67 
Artemisia  pauciflora,  807 


GENERAL    INDEX. 


945 


Artificial  camphor,  708 

respiration,  114 

respiration,     apparatus 

for,  (note)  114 
Artificially  digested  foods, 

13 

Asafetida,  75 
Asafoetida,  75 
Asagraea  officinalis,  370 
Aspic,  oil  of,  (note)  630 
Aspjdin,  (note)  811 
Aspidium,  8n 

spinulosum,  (note)  Sn 
Aspidosamine,  277 
Aspidosperma,  277 

quebracho-bianco,  277 
Aspidospermatine,  277 
Aspidospermine,  277 
Aspirin,  598 

Astragalus  gummifer,  783 
Astringents,  401 
Atomization,  65,  732 
Atoxyl,  483 

Atropa  belladonna,  168 
Atropina,  168 
Atropinae  sulphas,  184 
Atropine,  168 

poisoning  by,  183 

sulphate,  184 
Aurantii  amari  cortex,  629 

dulcis  cortex,  630 

flores,  630 
Auri  et    sodii    chloridum, 

497 

Ava,  715 
Azedarach,  806 


Baked  flour  porridge,  12 
Balm,  630 

of  Gilead,  708 
Balsam  of  Peru,  736 

of  Tolu,  736 
Balsamum    peruvianum, 

736 

tolutanum,  736 

traumaticum,  863 
Banks  oil,  515 
Bantingism,  22 
Barbadoes  aloes,  664 
Barbaloin,  664 
Barberry,  623 
Barley,  785 

water,  785 
Barosma  betulina,  704 

cernata,  704 
Basilicon  ointment,  708 
Bassorin,  783 
Bearberry,  705 
Beef  essence,  9 

tea,  9 
Belladonna,  168 

leaf,  168 

plaster,  184 


Belladonna  poisoning,  183 

root,  1 68 
Belladonnas  folia,  168 

radix,  168 
Benzaconine,    374,    (note) 

380 

Benzaldehyde,  394 
Benzaldehydum,  394 
Benzine,  (note)  106 
Benzojc  acid,  86 1 
Benzoin,  861 

Benzoinated  lard,  786,  863 
Benzoinum,  86 1 
Benzosulphinidum,  791 
Benzoyl-acetyl-peroxide, 

830 

Benzoyl-tropein,  117 
Benzozone,  830 
Berberine,  623,  756 
Berberis,  623 

vulgaris,  623 

Bertoni's  ether,  (note)  252 
Beta-eucaine,  117 
Beta-naphtol,  850 
Beta-naphtol-ether    salicyl- 

ate,  852 

Beta-oxysantonin,  808 
Betol,  852 

Bichloride  of  mercury,  821 
Bile,  655 

effects  of  drugs  on,  646 
Biniodide  of  mercury,  822 
Bismuth,  423 

and  ammonium  citrate, 

425 

citrate,  425 

oxyiodide,  427 

oxyiodpgallate,  426 

poisoning,  424 

salicylate,  427 

subcarbonate,  423 

subgallate,  426 

subnitrate,  423 

subsalicylate,  426 

tetraiodophenolphtha- 

lein,  515 
Bismuthi  citras,  425 

et  ammonii  citras,  425 

subcarbonas,  423 

subgallas,  426 

subnitras,  423 

subsalicylas,  426 
BismuthutTii  423 
Bisulphites,  865 
Bitter  almonds,  394 

cucumber,  671 

orange  peel,  629 
Bitters,  622 
Black  draught,  667 

drink,  (note)  338 

drop,  141 

ginger,  627 

haw,  744 

manganese  oxide,  741 

mustard,  772 

oak  bark,  408 
60 


1  Black  pepper,  628 

snakeroot,  78 

wash,  496 
Blackmail's  disinfectant, 

(note)  825 

Bleaching  powder,  823 
Blisters,  766 
Bloodroot,  739 
Blue  galls,  406 

mass,  493,  660 

ointment,  492 

pills,  493 

stone,  429 
Boletus,  409 

laricis,  409 
Boneblack,  819 
Bone-marrow,  531 
Bonjean's  ergotin,  756 
Boracic  acid,  866 
Borax,  866 
Boric  acid,  866 
Borneo    camphor,     (note) 

76 

Bornylamin,  (note)  283 
Boroglycerin,  869 
Bougies,  65 
Bran, 654 
Brandy,  289 
Brassica  alba,  772 

nigra,  772 
i  Brayera,  807 
;  Bread-and-milk  poultice, 

794 

Bromal  hydrate,  251 
Bromalin,  251 
Bromated  camphor,  79,  251 
Bromethylformin,  251 
Bromides,  comparative 

power  of,  250 
Bromine,  781 

as  a  disinfectant,  824 
Bromipin,  251 
Bromism,  241 
Bromocoll,  251 
Bromoform,  250 
Bromoformum,  250 
Bromolein,  250 
Bromum,  781 
Broom  plant,  350 
Broth,  chicken,  9 
Brown  mixture,  784 

stock,  10 

sugar,  654 
Brown-Sequard's     elixir, 

.  53i 
Brucine,  212,  227 

nitrate,  227 

sulphate,  227 
Bubonic    plague    serum, 

549 

Buchu, 704 
Buckthorn,  655 
Burgundy  pitch,  775 
pitch  plaster,  775 
Burnt  alum,  781 
Butyl-chloral  hydrate,  165 


946 


GENERAL    INDEX. 


Cabinet  baths,  (note)  717 
Cacao  butter,  787 
Cacodylic  acid,  482 
Caffeina,  338 

citrata,  339 

citrata  effervescens,  339 
Caffeine,  338 

poisoning,  348 
Caffeol,  (note)  340 
Caffeone,  (note)  339 
Cajuput,  629 
Calabar  bean,  229 
Calabarine,  229 
Calabarinum  puruni,(note) 

231 

Calamine,  428 
Calcii  bromidum,  249 
Calcii    carbonas     praecipi- 
tatus,  803 

chloridum,  803 

hypophosphis,  521 

iodidum,  804 

phosphas  pnecipitatus, 
520 

sulphas  exsiccatus,  803 
Calcium,  801 

bromide,  249 

carbonate,  803 

chloride,  803 

hypophosphite,  521 

iodide,  804 

lactophosphate,  520 

phosphate,  519 

precipitated,  520 

sulphate,  803 

sulphide,  658 
California  buckthorn,  655 
Calomel,  493,  660,  682 
Caloric,  28 
Calumba,  623 
Calx,  801 

chlorinata,  824 

sulphurata,  658 
Cambogia,  674 
Campherol,  (note)  283 
Camphor,  283 

artificial,  708 

bromated,  79 

cymol,  (note)  283 

liniment,  288 

-menthol,  (note)  852 

mixture,  Hope's,  455 

mqnobromated,  251 

poisoning,  288 

water,  288 
Camphora,  283 

monobromata,  79 
Camphorated    tincture    of 

opium,  141 
Camphoric  acid,  288 
Canada  balsam,  708 

fleabane,  707 

turpentine,  708 
Canadian  hemp,  333 


Canadine,  756 
Cannabene,  192 

tannate,   195 
Cannabin,  191 
Cannabinol,  192 
Cannabinon,  191 
Cannabis  indica,  191 
Canquoin's  paste,  779 
Cantharjdal  collodion,  772 
Cantharides,  714,  742,  769 

cerate,  772 

poisoning,  771 
Cantharidin,  769 

salts,  (note)  771 
Cantharis,  714,  769 

vesicatoria,  769 
Cape  aloes.  664 
Capsicin,  (note)  629 
Capsicum,  628,  773 

annuum,  629 

fastigiatum,  628 
Capsules,  69 
Caraway,  630 
Carbamic  ether,  163 
Carbazotic  acid.  814 
Carbo,  819 

animalis,  819 

purificatus,  819 

ligni,  819 
Carbolic  acid,  831 

poisoning,  838 
Carbon  bisulphide,  775 

compounds,  831 
Carbonei  disulphidum,  775 
Cardamom,  627 
Cardamomum,  627 
Cardiac  depressants,  359 

massage,  115 

stimulants,  279 
Cardiants,  279 
Carica  papaya,  817 
Carminatives,  625 
Carolina  jessamine,  264 
Carrageen,  783 
Carrageenin,  783 
Carron  oil,  802 
Carum,  630 

carui,  630 
Caryophyllus,  626 
Cascara  sagrada,  655 
Cassia  acutifolia,  666 

angustifolia,  666 

bark,  626 

fistula,  656 

obovata,  666 
Castile  soap,  765 
Castillon's  powder,  803 
Castor  oil,  659 

oil  beans,  659 
Cataplasm  of  kaolin,  793 
Cataplasma  kaolini,  793 
Catechu,  407 
Cathartic  acid,  666 
Cathartics,  644 
Caustic  potash,  777 

soda,  800 


Cayenne  pepper,  628 
Centric  emetics,  635 

local  anaesthesia,  121 
Cephaeline,  635 
Cephaelis  acuminata,  635 

ipecacuanha,  635 
Cera  alba,  786 

flava,  786 

Cerasus  serotina,  624 
Cerata,  62 
Cerates,  62 
Ceratum  cantharidis,  772 

resinae,  708 

compositus,  708    • 
Cerebritis,  saturnine,  414 
Cerii  oxalas,  426 
Cerium  oxalate,  426 
Cetaceum,  786 
Cetraria,  785 

islandica,  785 
Cetraric  acid,  785 
Cetrarin,  785 
Cevadine,  366 
Ceylon  cinnamon,  626 
Chalk,  803 

mixture,  803 
Chamomile,  631 
Champagne,  309 
Charcoal,  819 

Charta  arsenicalis  compos- 
ita,  (note)  732 

sinapis,  773 
Chartae,  62 
Chemical  current,  47 
Chenopodium,  806 

anthelminticum,  806 
Chicken  broth,  9 
Children,  comparative  dose 

for,  65 

Chili  saltpetre,  694 
Chillies,  628 
Chimaphila,  706 

umbellata,  706 
Chimaphilin,  706 
Chinese  cinnamon,  626 
Chinic  acid,  701 
Chirata,  623 
Chloral,  146 

hydrate,  146 

intravenous    injections 
of,  152 

poisoning,  152 

poisoning,  chronic,  153 
Chloralamid,  164 
Chloralformamid,  164 
Chloralformamidum,  164 
Chloralose,  165 
Chloralum  hydratum,  146 
Chloretone,  162 
Chloric  ether,  449 
Chlorinated  lime,  824 
Chlorine,  823 

water,  826 
Chloroform,  92 

liniment,  100 

water,  100 


GENERAL   INDEX. 


947 


Chloroformum,  92 
Chlorum,  823 
Chocolate  porridge,  12 
Cholera  antitoxin,  548 
Choline,  551 
Chondodendron    tomento- 

sum,  705 
Chondrus,  783 

crispus,  783 
Chromic  acid,  780 
Chromii  trioxidum,  780 
Chromium  trioxide,  780 
Chronic    antimony-poison- 
ing, 365 

arsenic-poisoning,  478 
chloral-poisoning,  153 
digitalis-poisoning, 

lead-poisoning,  412 
sulphonal-poisoning, 

157 

Chrysaroba,  765 
Chrysarobin,  765 
Chrysarobinum,  765 
Chrysophanic  acid,  662 
Chrysotoxin,  746 
Churrus,  191 
Cigarettes, arsenical,  (note) 

732 
Cimicifuga,  78 

racemosa,  78 
Cimicifugin,  78 
Cinchona,  555 

flava,  555 

pallida,  555 

rubra,  555 
Cinchonamine,  578 
Cinchonidinae    sulphas, 

57.8 
Cinchonidine,  578 

bromohydrate,  578 

sulphate,  578 
Cinchoninae  sulphas,  577 
Cinchonine,  577 

sulphate,  577 
Cinnaldehydum,  626 
Cinnamic  acid,  864 

aldehyde,  626 
Cinnamomum,  626 

saigonicum,  626 

zeylanicum,  626 
Cinnamon,  626 

water,  626 

Citrated  caffeine,  339 
Citric  acid,    395,    (note) 

453 

Citrine  ointment,  496 
Citrullus  colocynthis,  671 
Clarke's   Rule  for    Doses, 

(note)  66 
Classification,  70 
Claviceps  purpurea,  745 
Clear  stock,  10 
Clove  tea,  627 
Cloves,  626 
Coca,  195 


Cocainae    hydrochloridum, 

207 
Cocaine,  196 

habit,  209 

hydrochloride,  207 

poisoning,  207 
Cocainismus,  209 
Coca-tannic  acid,  196 
Codeina,  141 
Codeinae  phosphas,  141 

sulphas,  141 
Codeine,  141 

phosphate,  141 

sulphate,  141 
Cod-liver  oil,  577 
Coffee,  338,  (note)  339 
Cohnheim's  salt  frog,  150 
Colchiceine,  (note)  521 
Colchici  cormus,  521 

semen,  521 
Colchicina,  527 
Colchicine,  521,  527 
Colchicum,  521 

autumnale,  521 

poisoning,  526 

root,  521 

seed,  521 
Cold,  30 

as  a  diuretic,  678 

as  an  antiseptic,  820 

as  a  tonic,  32 

bath,  36 

cream,  409,  786 

in  pyrexia,  32 

local  use  of,  30 

physiological  action  of, 

32 

Colica  pictonum,  413 
Collargol,  439 
Collodion,  796 
Collodium,  796 

cantharidatum,  772 

flexile,  796 

stypticum,  405 
Colloidal  silver,  439 
Colocynth,  671 
Colocynth  in,  671 
Colocynthis,  671 
Columbian  spirits,  311 
Columbin,  623 
Columbo,  623 
Commercial    calcium    sul- 
phide, 658 

sodium  bicarbonate, 
801 

zinc  oxide,  427 
Compound  arsenical  paper, 
(note)  732 

cathartic  pills,  672 

decoction    of    sarsapa- 
rilla,  528 

extract  of    colocynth, 

671 
fluid  extract  of    sarsa- 

parilla,  529 
infusion  of  gentian,  623 


Compound  infusion  of  sen- 
na, 667 

jalap  powder,  670 
licorice    powder,    667, 

784 

mixture  of  iron,  448 
mixture  of  licorice,  784 
pills  of  rhubarb,  663 
powder  of  jalap,  680 
powder  of  rhubarb,  663 
solution  of  chlorine,  826 
solution  of  cresol,  848 
solution  of  iodine,  506 
spirit  of  ether,  76 
spirit  of  juniper,  707 
syrup     of     hypophos- 

phites,  528 
syrup    of   sarsaparilla, 

528 

syrup  of  squill,  737 
tincture  of  benzoin,  863 
tincture  of  cardamom, 

627 
tincture  of  cinchona, 

555 

tincture  of  gambir,  407 

tincture  of  gentian,  623 
Confectio  rosae,  409 

sennae,  667 
Confection  of  rose,  409 

of  senna,  667 
Confectiones,  62 
Confections,  62 
Conine,  269 

hydrobromate,  273 
Conium,  269 

maculatum,  269 

poisoning,  269,  273 
Consomme",  10 
Continuous  current,  46 
Convallamarin,  349 
Convallaria,  349 

maialis,  349 
Convallarin,  349 
Convolvulin,  670,  671 
Convolvulus      scammonia, 

671 
Copaiba,  712 

langsdorffii,  712 

-red,  713 

Copaivic  acid,  712 
Copper,  428 

arsenite,  479 

poisoning,  429 

sulphate,  428,  781 
Copperas,  823 
Coriander,  630 
Coriandrum,  630 

sativum,  630 
Cornutine,  746 
Corrosive    mercuric    chlo- 
ride, 494 

sublimate,  494 

as  a  caustic,  779 
as  a  disinfectant, 
821 


948 


GENERAL    INDEX. 


Corsican  moss,  785 
Corynanthe  yohimbi,  715 
Cosmoline,  792 
Cotarnine  gauze,  410 

hydrochlorate,  409 
Cotton-root,  764 

-seed  oil,  787 
Couch-grass,  706 
Counter-irritants,  766 
Court-plaster,  796 
Coxe's  hive  syrup,  737 
Cracked  wheat,  654 
Cramp-root,  744 
Cream  of  tartar,  693 
Creasote,  842 
Creolin,  849 
Creosotal,  845 
Creosote,  842 

carbonate,  845 

water,  845 
Creosotum,  842 

carbonicum,  845 
Cresalol,  849 
Cresol,  848 

salicylate,  849 
Cresylic  acid,  848 
Cresylol,  848 
Creta,  803 

prseparata,  803 
Croton-chloral,  165 

oil,  675 

tiglium,  675 
Crotonoleic  acid,  675 
Croton-resin,  675 
Crude  camphor,  283 
Cryptopine,  142 
Crystallized  digitalin,  312 
Cubeb,  713 
Cubeba,  713 
Cubebic  acid,  713 
Cubebin,  713 
Cupri  sulphas,  428,  874 
Cuprum,  428 
Cusso,  807 
Cyanogen  gas,  394 
Cynips  galte  tinctorise,  406 
Cypripedin,  79 
Cypripedium,  79 

parviflorum,  79 

pubescens,  79 
Cytisine,  372 
Cytisus  laburnum,  372 

scoparius,  350,  682 


Dandelion,  530 
Daphne  mezereum,  529 
Daphnin,  529 
Datura  stramonium,  185 
Daturine,  185 
Decocta,  60 
Decoction  of  kava,  715 
sarsaparilla,      com- 
pound, 528 


Decoctions,  60 

Delirifacients,  168 

Demulcents,  782 

Deodorized  opium,  140 
tincture  of  opium,  141 

Depresso-motors,  229 

Depurant  diuretics,  687 

Dermatol,  426 

Dewees's  emmenagogue 
mixture,  742 

Diaethylsulfondimethylme- 
than,  155 

Diagnosis,  use  of  electricity 
in,  52 

Dialyzed  iron,  450 

Diaphoretics,  717 

Diastase,  817 

Diet,  22 

Diethylendiamine,  698 

Di-fluor-diphenyl,  865 

Digestants,  815 

Digested  foods,  13 

Digitalein,  312 

Digitalin,  312,  332 
crystallized,  312 
German,  312 
of  Kiliani,  312 

Digitalinum     crystallatum, 

312 

Gallicum,  312 
Germanicum,  312 
verum,  312 

Digitalis,  312 

as  a  diuretic,  686 
eriostachys,  (note)  312 
ferruginea,  (note)  312 
fontanesii,  (note)  312 
gigantea,  (note)  312 
glandulosa,  (note)  312 
nervosa,  (note)  312 
poisoning  by,  328 
purpurea,  312 

Digitin,  312 

Digitonin,  312 

Digitoxin,  312,  332 

Dihydroxyl-qumine,  (note) 
56i 

Diiodoparaphenolsul- 
phonic  acid,  515 

Di-isobutyl-ortho-cre-sol- 
iodide,  515 

Dilute  acetic  acid,  397 
alcohol,  289 
hydriodic  acid,  508 
hydrobromic  acid,  249 
hydrochloric  acid,  454 
hydrocyanic  acid,  385, 

.393 

nitric  acid,  455 
nitro-muriatic  acid,  455 
phosphoric  acid,  518 
prussic  acid,  393 
silver  nitrate,  438 
solution  of  lead  subace- 

tate,  422 
sulphuric  acid,  454 


Dimethylamidophenyl-di- 
methylpyrazolon,  617 

Dimethylarsenic  acid,  482 

Dimethylpiperazine      tar- 
trate,  699 

Dimethylxanthine,  683 

Dinner-pill,  666 

Dionine,  142 

Dioxypurin,  683 

Diphtheria  antitoxin,  545 

Disinfectants,  820 

proprietary,  (note)  825 

Di-steary  1-glycerophos- 

phate  of  cholin,  550 

Distilled  oils,  61 

Disulphones,  155 

Dithymol-diiodide,  514 

Diuretics,  678 

Diuretin,  684 

Donovan's  solution,  507 

Dormiol,  163 

Doses,  rules  for,  65 

Dover's  powder,  140,  728 

Drastics,  670 

Dried  alum,  410 
•    blood,  445 

calcium  sulphate,  803 
ferrous  sulphate,  449 
sodium  carbonate,  801 
suprarenals,  543 
thyroid  body,  538 

Dry   heat  as  a  germicide, 
820 

Dryobalanops   camphora, 
(note)  76 

Dryopteros  filix  mas,  811 
marginale,  811 

Ductless  glands,  534 

Dunbar's    hay-fever    anti- 
toxin, 549 

Duotal,  846 


Ebstein  method,  23 

Ecballium  elaterium,  673 

Effervescent  titrated  caf- 
feine, 339 

lithium  citrate,  698 
magnesium  citrate, '668 
magnesium     sulphate, 

668 
sodium  phosphate,  669 

Effervescing  draught,  692 

Eggnog,  ii,  310 

Elaterin,  673 

Elaterinum,  673 

Elaterium,  673 

Electric  brush,  52 

Electricity,  41 

therapeutic  application 

of,  52 
use  of,  as  a  tonic,  58 

Elettaria  repens,  627 

Elixir  adjuvans,  784 


GENERAL    INDEX. 


Elixir  of  phosphorus,  468 
of  testicles,  531 
of  valerianate  of   am- 
monium, 75 
phosphori,  468 
proprietatis,  666 

Emetics,  632 

Emetine,  635,  639 

Emmenagogues,  741 

Emodin,  663 

Emollients,  786 

Emplastra,  62 

Emplastrum    ammoniaci 

cum  hydrargyro,  739 
adhaesivum,  796 
belladonnas,  184 
hydrargyri,  493,  496 
plumbi,  421,  796 
resinae,  421,  708 
saponis,  421,  796 

Empyreumatic  oils,  61 

Emulsin,  624,  772 

Emulsion  of  ammoniac,  739 
of  asafetida,  76 
of  chloroform,  100 
of  cod-liver  oil,  518 
of    cod-liver    oil    with 
hypophosphites,   518 
of  oil  of  turpentine,  712 

Emulsions,  61 

Emulsum  ammoniaci,  739 
asafcetidae,  76 
chloroform!,  100 
olei  morrhuae,  518   . 
cum  hypophos- 

phitum,  518 
terebinthinae,  712 

Encephalopathia  saturnina, 
414 

Endermic    administration, 

65 

Enemata,  649 
high,  650 
nutritive,  14 

English  garlic,  733 

Eosote,  847 

Epinephrin,  540 

Epispastics,  769 

Epsom  salt,  667 

Ergot,  745 

Ergota,  745 

Ergotin,  746,  '756 

Ergotism,  755 

Erigeron,  707 

canadense,  707 

Erythrol  tetranitrate,  262 

Erythroxyline,  195 

Ery thro xy Ion  coca,  195 

Escharotics,  776 

Eserine,  229 

Essence  of  beef,  9 
of  ginger,  628 
of  peppermint,  630 
of  spearmint,  630 

Essential    salt   of    lemons, 
398 


Ether,  87 

Bertoni's,  (note)  252 

pneumonia,  (note)  108 
Ethereal  oil,  61,  76 
Ethyl  bromide,  100 

carbamate,  163 

chloride,  100 

ester  of    p-amidoben- 
zoic  acid,  118 

nitrite,  260,  728 

oxide,  87 
Ethylacetamidopheno  1 , 

(note)  611 

Ethylene  bromide,  101 
Eucaine,  117 

Eucalypsinthe,  (note)  582 
Eucalyptol,  582 
Eucalyptus,  582 

globulus,  582 

gum,  582 
Eudoxine,  515 
Eugenia  aromaticus,  626 

jambolana,  529 
Eugenol,  860 
Euonymin,  656 
Euonymus,  655 

atropurpureus,  655 
Eupyrin,  610 
Equmine,  559 
European  rhubarb,  662 
Europhen,  515 
Exalgine,  616 
Excito-motors,  212 
Expectorants,  729 

of  the  first  group,  733 

of  the  second  group, 

734 
of  the  third  group,  735 

Expressed  oil  of  almonds, 
787 

Extract  of  aconite,  385 
of  aloes,  666 
of   belladonna  leaves, 

alcoholic,  184 
of  bone-marrow,  531 
of  Calabar  bean,  238 
of  cannabis  indica,  195 
of  cascara  sagrada,  655 
of  chirata,  623 
of  cimicifuga,  79 
of  colchicum  root,  527 
of  colocynth,  671 
of  conium,  273 
of  dandelion,  530 
of  digitalis,  330 
of  ergot,  756 
of  euonymus,  656 
of  gentian,  622 
of  glycyrrhiza,  784 
of  heematoxylon,  408 
of  hemp,  195 
of  hyoscyamus,  186 
of  Indian  cannabis,  195 
of  krameria,  408 
of  licorice,  784 
of  logwood,  408 


Extract  of  malt,  816 

of  nux  vomica,  212 

of  opium,  140 

of  physostigma,  238 

of  quassia,  622 

of  rhatany,  408 

of  rhubarb,  663 

of  spleen,  531 

of    stramonium     seed, 
185 

of  sumbul,  80 

of  syzygium    jambola- 
num,  (note)  398 

of  taraxacum,  530 

of  uva  ursi,  706 

of  wahoo,  656 
Extracta,  61 
Extracts,  fluid,  62 

solid,  61 
Extractum  aloes,  666 

belladonnae    foliorum, 
184 

cannabis  indicae,  195 

cimicifugae,  79 

colchici  cormus,  527 

colocynthidis,  671 

colocynthidis  composi- 
tum,  671 

conii,  273 

digitalis,  330 

ergotae,  756 

euonymus,  656 

gentianae,  623 

glycyrrhizae,  784 
purum,  784 

haematoxyli,  408 

hyoscyami,  186 

krameriae,  408 

lactucarii  fluidum,  84 

malti,  816 

nucis  vomicae,  2 1 2 

opii,  140 

pnysostigmatis,  238 

quassiae,  622 

rhamni  purshianae,  655 

rhei,  663 

spigeliae  et  sennae  flui- 
dum, 806 

stramonii,  185 

sumbul,  80 

taraxaci,  530 
Extraneous  remedies,  797 


Factitious  scammony,  671 
Fagus  sylvatica,  842 
Farad  ic  current,  47 
Faradization,  general,  59 
Feeding  by  the  rectum,  14 

of  the  sick,  6 
Fel  bovis,  655 

purificatum,  655 
Fell's  apparatus,  (note)  114 
Fennel,  630 


950 


GENERAL    INDEX. 


Fennel  water,  630 
Ferratin,  445 
Ferri  carbonas  saccharatus, 
448 

chloridum,  450 

citras,  451 

et  ammonii  citras,  451 

et    ammonii    sulphas, 

45i 

et  ammonii  tartras,  451 
et  potassii  tartras,  451 
et  quininae  citras,  451 
et  quininae  citras  solu- 

bilis,  451 
et    strychninae    citras, 

451 

hydroxidum,  448 

hydroxidum  cum  mag- 
nesii  oxido,  448 

hypophosphis,  451,  521 

iodidum   saccharatum, 
450 

lactas,  451 

phosphas  solubilis,  451 

pulvis,  448 

pyrpphosphas   solu- 
bilis, 451 

sulphas,  449 

sulphas  exsiccatus,  449 

sulphas    granulatas, 

449 
Ferric  ammonium  sulphate, 

45i 

chloride,  450 
citrate,  451 
hydrate,  448 
hydrate  with  magnesia, 

448 

hypophosphite,  521 
phosphate,  soluble,  451 
pyrophosphate,      solu- 
ble, 451 
subsulphate,      solution 

of,  449 
sulphate,    solution   of, 

449 
Ferrous  carbonate,  saccha- 

rated,  448 
iodide,    saccharated, 

45o 

lactate,  451 
sulphate,  449,  823 
sulphate,  dried,  449 
Ferrum,  443 

dialyzatum,  450 
reductum,  448 
Ferula  foetida,  75 

sumbul,  80 
Ficus,  654 
Figs,  654 
Filicic  acid,  811 
Filix  mas,  811 
Fire,  820 
Flake  manna,  655 
Flaxseed,  784 
poultice,  794 


Flaxseed  tea  (infusion),  784 

Fleabane,  707 

Fleming's  tincture  of  aco- 
nite, 385 

Flexible  collodion,  796 

Fluidextract  of  aconite,  385 
of  apocynum,  334 
of  belladonna  root,  184 
of  bitter  orange  peel, 

629 

of  black  haw,  744 
of  buchu,  705 
of  calumba,  623 
of  cannabis  indica,  195 
of  capsicum,  629 
of  cascara  sagrada,  655 
of  chimaphila,  706 
of  chirata,  623 
of  cimicifuga,  79 
of  cinchona,  555 
of  coca,  207 
of    colchicum     seeds, 

527. 

of  conium,  273 
of  convallaria,  350 
of  couch-grass,  706 
of  cramp-root,  744 
of  cubeb,  714 
of  dandelion,  530 
of  digitalis,  330 
of  ergot,  756 
of  eucalyptus,  582 
of  euonymus,  655 
of  frangula,  655 
of  gelsemium,  267 
of  gentian,  623 
of  geranium  409 
of  ginger,  628 
of  glycyrrhiza,  784 
of  grindelia,  736 
of  hamamelis,  408 
of  hemp,  195 
of  hydrastis,  760 
of  hyoscyamns,  186 
of  Indian  cannabis,  195 
of  ipecacuanha,  639 
of  jaborandi,  727 
of  kava,  715 
of  krameria,  408 
of  lactucarium,  80 
of  leptandra,  656 
of  licorice,  784 
of  lobelia,  264 
of  lupulin,  78 
of  matico,  714 
of  mezereon,  529 
of  nux  vomica,  212 
of  oak  bark,  409 
of  pareira  brava,  705 
of  pilocarpus,  727 
of  pomegranate,  813 
of  podophyllum,  673 
of  quassia,  622 
of  rhamnus  purshiana, 

655 
of  rhatany,  408 


Fluidextract  of  rhubarb,  663 
of  rhus  glabra,  409 
of  rose,  409 
of  sanguinaria,  739 

of  sarsaparilla,  529 
of  savine,  742 
of  scopola,  187 
of  senega,  739 

of  senna,  667 

of  serpentaria,  631 

of  spigelia,  806 

of  spigelia  and  senna, 
806 

of  squill,  682 

of  stillingia,  530 

of  stramonium,  185 

of  sumach,  409 

of  sumbul,  80 

of  taraxacum,  530 

of  uva  ursi,  706 

of  valerian,  75 

of  veratrum,  370 

of  wild  cherry,  624 

of  xanthoxylum,  530 
Fluidextracta,  62 
Fluidextracts,  62 
Fluidextractum  aconiti,  385 

apocyni,  334 

aromaticum,  626 

aurantii  amari,  629 

belladonnas  radicis,  184 

berberidis,  624 

buchu,  705 

calumbae,  623 

cannabis  indicae,  195 

capsici,  629 

chimaphilae,  706 

chiratae,  623 

cjmicifugae,  79 

cinchonae,  555 

cocae,  207 

colchici  seminis,  527 

conii,  273 

convallariae,  350 

cubebae,  714 

cypripedii,  79 

digitalis,  330 

ergotae,  756 

eucalypti,  582 

euonymi,  655 

frangulae,  655 

gelsemii,*267 

gentianae,  623 

geraniae,  409 

glycyrrhizae,  784 

granati,  813 

grindeliae,  736 

hamamelidis  foliorum, 
408 

hydrastis,  760 

hyoscyami,  186 

ipecacuanhae,  639 

krameriae,  408 

lactucarii,  80 

leptandrae,  656 

lobelia;,  264 


GENERAL    INDEX. 


Fluidextractum  lupulini,  78 

matico,  714 

mezerei,  531 

nucis  vomicae,  212 

pareirae,  705 

pilocarpi,  727 

podophylli,  673 

pruni  Virginianae,  624 

quassiae,  622 

quercus,  409 

rhamni  purshianae,  655 
aromaticum,  655 

rhei,  663 

rhois  glabrae,  409 

rosae,  409 

sabinae,  742 

sanguinariae,  739 

sarsaparillae,  529 

compositum,  529 

scillae,  682 

scopolae,  187 

senegae,  739 

sennas,  667 

serpentariae,  631 

spigeliae,  806 

stilhngiae,  530 

stramonii,  185 

sumbul,  80 

taraxaci,  530 

tritici,  707 

uva  ursi,  706 

valerianse,  75 

veratri,  370 

viburni  opuli,  744 

viburni  prunifolii,  746 

xanthoxyli,  53 

zingibens,  628 
Fluorides,  865 
Fluoroform,  866 
Fluoroformol,  866 
Fluorol,  865 
Fceniculum,  630 

capillaceum,  630 
Foods,  artificially  digested, 

13 

composition  of,  23 
Forced     artificial     respira- 
tion, 114 

enemata,  639 

insufflation,  114 
Formaldehyde,  855 
Formalin,  856 
Formin,  699 
Formol,  855 
Formyl,  855 

bromide,  250 
Fowler's  solution,  482 
Foxglove,  312 
Frangula,  655 
Frangulin,  655 
Fraxmus  ornus,  655 
French  digitalin,  312 
Fresh  juices,  61 
Fuller's  earth,  793 
Fumigations,   mercurial, 
492 


Furfur-alcohol,  (note)  340 
Fused  silver  nitrate,  431 


Gaduin,  516 
Gadus  morrhua,  515 
Galla,  406 
Gallic  acid,  406 
Gallo-tannic  acid,  402 
Galls,  406 
Galvanic  current,  47 
Galvanization  of  the  spinal 
cord,  58 

of  the  sympathetic,  58 
Gambir,  407 
Gamboge,  674 

in  sorts,  675 

Gangrenous  ergotism,  755 
Garcinia  hanburii,  674 
Garden  rue,  742 
Garlic,  736 
Gaulthena,  597 
Gelatin,  532 

tannate,  405 
Gelatinum,  532 

glycerinatum,  534 
Gelatose  silver,  438 
Gelsemin,  (note)  265 
Gelsemine,  264 
Gelseminic  acid,  264 
Gelseminin,  (note)  265 
Gelsemium,  264 

sempervirens,  264 
General  faradization,  59 
Gentian,  622 
Gentiana,  622 

lutea,  622 
Gentiopikrin,  622 
Gentisic  acid,  622 
Geosote,  847 
Geranium,  409 

maculatum,  409 
German  chamomile,  631 

digitalin,  312 
Germicides,  820 
Gigartina  mamillosa,  783 
Gin,  707 
Ginger,  627 
Glacial  acetic  acid,  397 
Glandulae  suprarenales,  538 
siccae,  543 

thyroideae,  534 
siccae,  538 
Glauber  salt,  668 
Glonoin  trinitrate,  262 
Glucose,  687 
Glusidum,  791 
Glycerin,  788 
Glycerinated  gelatin,  534 
Glycerinum,  788 
Glycerita,  61 

Glycerite  of  boroglycerin, 
869 

of  hydrastis,  760 


Glycerite  of  starch,  785,  791 
of  tannin,  405 
of  yolk  of  egg,  791 

Glycentes,  61 

Glyceritum   acidi    tannici, 

405 

amyli,  785 
boroglycerini,  869 
hydrastis,  760 
phenolis,  841 
Glycero-phosphoric     acid, 

519 

Glyceryl  nitrate,  261 
Glyco-formalin,  858 
Glycosal,  599 
Glycyrrhiza,  784 

glabra,  784 

glandulifera,  784 
Glycyrrhizin,  784 
Glycyrrhizinum    ammonia- 
turn,  784 
Goa  powder,  766 
Gold  and  sodium  bromide, 
250 

chloride,  497 

iodide,  498 

oxide,  498 
Golden  seal,  756 
Gossypii  cortex,  764 
Gossypium  herbaceum,  764 

purificatum,  764 
Goulard's  extract,  422 
Granatum,  813 
Gray  powder,  493 
Green  galls,  406 

ginger,  627 

soap,  765 

Griffith's  mixture,  448,  741 
Grindelia,  735 

robusta,  735 

squarrosa,  735 
Ground  slippery  elm,  794 
Guaiac,  742 

resin,  529 

Guaiaci  resina,  529 
Guaiacol,  845 

carbonate,  846 
Guaiacolis  carbonas,  846 
Guaiaconic  acid,  502 
Guarana,  330 
Tiuaranine,  (note)  339 
}um  arabic,  782 
jun-cotton,  796 
iunjah,  191 
iutta-percha,    796 


H 

rtaematin,  407 
Haematogen,  445 
[-laematoporphyrin,  157 
hlaematoxylin,  407 
Hasmatoxylon,  407 

campechianum,  407 
laemoglobin,  445 


952 


GENERAL    INDEX. 


Hagenia  abyssinica,  807 
Halogen  disinfectants,  823 
Hamamelidis  cortex,  408 

folia,  408 
Hamamelin,  408 
Hamamelis,  408 

Virginica,  408 
Hashish,  191 
Hay-fever  antitoxin,  549 
Heat  as  a  disinfectant,  820 
Heavy  magnesia,  656 

oil  of  wine,  76 
Hedeoma  pulegioides,  743 
Hedonal,  163 
Helmitol,  701 
Hemp,  191 
Heroine,  144 
Heteroxanthin,  684 
Hetol,  864 
Hetralin,  701 
Hexamethylenamina,  699 
Hexamethylenetetramine, 

699 

High  enemata,  650 
Hippurate     of     lime    and 

lithia,  (note)  861 
Hippuric  acid,  861 
Hive  syrup,  Coxe's,  737 
Hoffmann's  anodyne,  76 
Holly  tea    (note)  338 
Homatropinae  hydrobro- 

midum,  190 
Homatropine,  190 

hydrobromide,  190 
Honey  of  rose,  409 
Honeys,  61 
Hop  poultice,  78 
Hope's  camphor  mixture, 

455 

Hops,  77 
Hordeum,  785 
Horehound,  739 
Hot  baths,  30,  717 
Humulus,  77 

lupulus,  77 

Hundred-leaved  rose,  409 
Huxham's  tincture,  555 
Hydragogue  diuretics,  6So 
Hydragogues,  653 
Hydrargyri  chlondum  cor- 
rosivum,  493,  779,  821 
chloridum  mite,  493 
iodidum  flavum,  495 
rubrum,  495,  822 
oxidum  flavum,  496 

rubrum,  496 
Hydrargyrum,  483,  659 
ammoniatum,  496 
cum  creta,  493 
Hydrastin,  756 
Hydrastina,  760 
Hydrastine,  756,  760 
Hydrastininse      hydrochlo- 

ras,  761 

Hydrastinine       hydrochlo- 
rate,  761 


Hydrastis,  756 

canadensis,  756 
Hydrated  oxide  of  iron,  448 
Hydrobrpmic  acid,  249 
Hydrochinone,  705,  854 
Hydrochloric  acid,  454 
poisoning,  452 
Hydrocyanic  acid,  385 

poisoning  by,  392 
Hydrofluoric  acid,  865 
Hydrogen     dioxide,    solu- 
tion of,  828 

peroxide,    solution  of, 

828 

Hydroquinone,  854 
Hydroxybenzene,  831 
Hyoscinae  hydrobromidum, 

187 
Hyoscine,  185,  187 

hydrobromide,  187 
Hyoscyaminae  sulphas,  186 
Hyoscyamine  sulphate,  186 
Hyoscyamus,  185 

niger,  138,  185 
Hyperemesis,  634 
Hypnone,  164 
Hypochlorites,  824 
Hypodermic  injections,  64 

purgation,  651 
Hypodermoclysis,      (note) 

209,  678 

Hypophosphites,  521 
Hypophosphorous       acid, 

520 

Hypophysis,  543 
Hypoquebrachine,  377 


Ice-poultice,  31 
Iceland  moss,  785 
Ichthalbin,  528 
Ichthargan,  440 
Ichthyodin,  528 
Ichthyol,  527 

albuminate,  528 
Idiosyncrasies,  66 
Igasuric  acid,  212 
Ignis  sacer,  755 

sancti  Antonii,  755 
Ilex  cassine,  (note)  338 

Paraguaiensis,     (note) 

338 

Illicmm  amsatum,  630 
Impure  haemoglobin,  445 
Incompatibilities,  69 
Index  of  diseases,  889 
India  senna,  666 
Indian  cannabis,  191 

hemp,  191 

meal,  654,  794 
Indications  for  drugs,  62 
Induced  current,  47 
In6e  poison,  334 
Infiltration-anaesthesia,  119 


Infusa,  61 

Infusion  of  chamomile,  631 

of  cloves,  627 

of  coffee,  (note)  318 

of  digitalis,  330 

of  gentian,  compound, 

,6.23. 
or  jumper,  707 

of  pareira  brava,  705 

of    senna,    compound, 
667 

of  wild  cherry,  624 
Infusions,  61 
Infusum  digitalis,  330 

pruni  virginianae,  624 

sennae    compositum, 

667 
Injections,  65 

subcutaneous,  64 
Insoluble     gold     prepara- 
tions, 498 
Intravenous    injections    of 

chloral,  152 
salt  solution  in  poi- 
soning, (note) 
209 

Inunctions,  mercurial,  491 
lodic  acid,  (note)  512 
Iodine,  498 

as  a  disinfectant,  824 

ointment,  504 
lodipin,  508 
lodism,  500 
lodoform,  508 

ointment,  513 

poisoning,  513 
lodoformogen,  515 
lodoformum,  508 
lodol,  514 
lodolum,  514 
lodothyrin,  535 
lodum,  498 
Ipecacuanha,  635 

as  a  diaphoretic,  728 

as  an  expectorant,  733 
Ipecacuanhic  acid,  635 
Ipomcea  jalapa,  670 
Irish  moss,  783 
Iron,  443 

and  ammonium  cit- 
rate, 451 

and  ammonium   tar- 
trate,  451 

and  potassium  tartrate, 

45i 

and  quinine  citrate,  451 
and  strychnine  citrate, 

451 

by  hydrogen,  448 
citrate,  451 
Quevenne's,  448 
tartrates,  451 
Irritants,  765 

and     counter-irritants, 

765 
Isacomtme,  374 


GENERAL    INDEX. 


953 


Isarol,  528 
Isinglass  plaster,  796 
Iso -butyl  nitrite,  (note)  244 
Isopelletierine,  813 
Isophysostigmine,  229 
Isopilocarpine,  (note)  721 
Isopral,  163 
Isopunicine,  813 
Itrol,  438 


Jaborandi,  720 
Jaborine,  (note)  721 
Jacket-poultice,  794 
Jaguarandy,  720 
Jalap,  670 
Jalapa,  670 
Jalapin,  671 
Jamaica  ginger,  628 
Jambul,  529 
Jamestown  weed,  185 

amguarandi,  720 

apaconitine,  (note)  374 
jateorhiza  palmata,  623 
"erusalem  oak,  806 

ervine,  366 

iiices,  6t 
Julienne  soup,  10 
Juniper,  707 
Juniperus,  707 

communis,  707 
sabina,  742 


Kaiserling's  solution,  859 
Kamala,  813 
Kaolin,  793 
Kava,  715 
Kava-kava,  715 
Kava  resin,  715 
Kavin,  715 
Kawa,  715 

Kentish  ointment,  774 
Kiliani's  digitalin,  312 
Kinic  acid,  555 
Kino,  407 

Kino-tannic  acid,  402 
Kinovic  acid,  555 
Kola  nut,  (note)  338 
Kombe"  poison,  334 
Kosin,  807 
Kosotoxin,  807 
Koumys,  n 
Kousso,  807 
Krameria,  408 

ixina.  408 

triandra,  408 
Kumys,  n 
Kuzazu,  (note)  374 


Labarraque's  solution,  825 
Lactic  acid,  (note)  394,  457 


Lactophosphate     of    lime, 

520 

Lactuca  virosa,  80 
Lactucarium,  80 
Lactucin,  80 
Lady  Webster  pills,  666 
Lanolin,  788 
Lard,  786 

Large  enemata,  650 
Largin,  438 
Laudanine,  142 
Laudanum,  141 
Laurus  camphora,  283 
Lavage  of  the  blood,  (note) 

209,  679 
Lavandula    spica,     (note) 

630 

Lavender,  oil  of,  630 
Laxatives,  654 
Lead,  411 

acetate,  421 

carbonate,  422 

chrpmate,  (note)  412 

colic,  413 

nitrate,  423,  823 

oleomargarate,  421 

oxide,  421 

plaster,  421,  796 

poisoning,  410 

water,  422 
Lecithin,  551 

Ledoyen's  disinfectant  so- 
lution, 423,  823 
Lemon-juice,  396 
Lemon-peel,  630 
Lemons,   essential  salt  of, 

398 

Leptandra,  656 
Leptandrin,  656 
Levant  wormseed,  807 
Lichen  starch,  785 
Lichenin,  785 
Lichenstearic  acid,  785 
Licorice,  784 

root,  784 

Liebig's  beef  tea,  9 
Light  magnesia,  656 
Lily  of  the  valley,  349 
Lime,  801, 

lactophosphate,  520 

liniment,  802 

stone,  801 

unslaked,  801 

water,  802 
Limonis  cortex,  630 
Liniment  of  ammonia,  775 

of  belladonna,  184 

of  camphor,  288 

of  chloroform,  100 

of  lime,  802 

of  soap,  288 

of  turpentine,  774 
Linimenta,  62 
Liniments,  62 
Linimentum  ammoniac,  775 

belladonnae,  184 


Linimentum  calcis,  802 
camphorae,  288 
chloroformi,  loo 
saponis,  288 
terebinthinae,  774 

Linseed  oil,  787 

Linum,  784 

usitatissimum,  784 

Liquid  cosmoline,  792 
meat  foods,  7 
petrolatum,  792 

Liquor  acidi  arsenosi,  482 
ammonii  acetatis,  728 
arseni  et  hydrargyri 

iodidi,  507 
calcii  oxidi,  802 
chlori  compositus,  826 
cresolis  compositus,  848 
ferri  chloridi,  450 
fern  subsulphatis,  449 
ferri  tersulphatis,  449 
formaldehydi,  856 
gutta-percnae,  796 
hydrargyri  nitratis,  779 
iodi  compositus,  504 
magnesii  citratis,  668 
pancreaticus,  13 
plumbi  subacetatis, 

421 
plumbi  subacetatis  di- 

lutus,  422 
potassae,  692 
potassii  arsenitis,  482 
potassii  citratis,  692 
sodae  chlorinatae,  825 
sodii  arsenatis,  482 
sodii  hydroxidi,  800 
zinci  chloridi,  779 

Liquores,  61 

Lisbon  diet-drink,  528 

Listerine,  874 

Litharge,  421 

Lithiasis,  24 

Lithii  benzoas,  698 

bromidum,  249,  698 
carbonas,  698 
citras,  698 
citras  effervescens,  698 

Lithium,  697 

arsenical    solution    of, 

698 

benzoate,  698 
bromide,  249 
carbonate,  698 
citrate,  698 
mercuric  iodide,  822 

Lobelia,  262,  733 
inflata,  262 

Lobeline,  262 

Local  anaesthesia,  117 
applications,   65 
cold,  30 
heat,  28 
remedies,  621 

Logwood,  407 

Lozenges,  62 


954 

Lozenges  of  ipecacuanha, 

63? 
of     ipecacuanha     and 

morphine,  639 
Lugol's  solution,  504 
Lump  asafetida,  75 
Lunar  caustic,  431 
Lupulin,  77 
Lupulinum,  77 
Lycetol,  699 
Lycoctonine,  (note)  374 
Lysol,  848 

M 

Mace,  627 
Macis,  627 
Macrotin,  78 
Magnesia,  656,  798 

ponderosa,  656 
Magnesii  carbonas,  656 

sulphas,  667 

sulphas     effervescens, 

668 
Magnesium  carbonate,    656 

citrate,  668 

sulphate,  667 
Magnetism,  59 
Male  fern,  81 1 
Malic  acid,  409 
Mallotus  philippinensis,  813 
Malt,  816 

Mammary  glands,  531 
Manganese,  451 

dioxide,  451,  741 

sulphate,  451 

Mangani    dioxidum    prae- 
cipitatum,  451 

sulphas,  451 
Manna,  655 
Mannite,  655 
Marble,  801 

Marjoram,  oil  of, (note)  630 
Marrubiin,  739 
Marrubium,  739 
Martineau's  solution,  (note) 

698 
Mass  of  copaiba,  713 

of  mercury,  493 
Massa  copaibae,  713 

hydrargyri,  493 
Massage,  2 

of  the  heart,  115 
Mat£,  (note)  338 

in  leaf,  (note)  338 

in  powder,  (note)  338 
Materia  medica,  60 
Maticin,  714 
Matico,  714, 
Matricaria,  631 

chamomilla,  631 
Matzoon,  12 
May-apple,  672 
Meadow  saffron,  521 
Measures   of   the  metrical 
system,  880 


GENERAL    INDEX. 

Meat-juice,  8 
Mechanical  emetics,  643 
Meconic  acid,  125 
Meconine,  125 
Medulla  sassafras,  785 
Mel  rosae,  409 
Melaleuca      leucadendron, 

629 

Melia  azedarach,  806 
Melissa,  630 

officinalis,  630 
Mellita,  61 
Mentha  piperita,  630 

pulegium,  743 

viridis,  630 
Menthol,  852 
Mercurial  cachexia,  487 

fumigations,  492 

inunctions,  491 

ointment,  492 

pills,  493 

plaster,  493 

poisoning,  local,  487 

ptyalism,  484 

purgatives,  660 
Mercuric    nitrate,   solution 
of,  765 

oxide,  496 
Mercury,  483,  682 

ammoniated,  496 

bichloride,  494,  821 

biniodide,  822 

hypodermic     use     of, 
492 

with  chalk,  493 
Mesotan,  599 
Meta-arsemc-anilid,  483 
Metacresol,  848 
Metallic  salts  as  disinfect- 
ants, 821 

Methaemoglobin,  256 
Methenyl  chloride,  92 
Methyl  alcohol,  311 

bromide,  102 

propyl-carbinol-ure- 
thane,  163 

pyrocatechin,  845 

salicylas,  597 

salicylate,  597 
Methylacetanilid,  617 
Methylal,  163 
Methylene  bichloride,    102 

blue,  580 
Methylic  alcohol,  311 

amblyopia,  311 
Methylthioninse         hydro- 

chloridum,  580 
Methylxanthine,  683 
Methysticin,  715 
Metric  system,  880 
Mezereon,  529 

ointment,  529 
Mezereum,  529 
Mild    mercurous   chloride, 

493 
Milk  diet,  26 


Milk  foods,  10 

of  asafetida,  76 

punch,  ii,  310 

toast,  pancreatized,  14 
Mineral  acids,  452 

astringents,  410 

tonics,  443 
Minor  hypnotics,  162 
Mistura  cretae,  803 

ferri     composita,    448, 

74i 

glycyrrhizae      compos- 
ita, 784 

potassii  citratis,  692 
rhei  et  sodae,  664 
Misturae,  61 
Mixed  anaesthetics,  (note) 

106 

Mixture  of  asafetida,  76 
of    potassium    citrate, 

680 
of  rhubarb  and  soda, 

664 

Mixtures,  61 
Moist  heat  as  a  germicide, 

820 

Molasses,  654 
Monobromated     camphor, 

79.  25i 

Monomethyl  ether,  845 
Monosalicylic-glycerin 

ester,  599 

Monsel's  solution,  450 
Morphina,  141 
Morphinae  acetas,  141 

hydrochloras,  141 

sulphas,  141 
Morphine,  125,  141 

acetate,  141 

benzyl-ester   hydro- 
chloride,  142 

derivatives,  142 

diacetic  ester,  144 

hydrochlorate,  141 

sulphate,  141 
Moschus,  73 

moschiferus,  73 
Motor  points,  51,  883 
Mucilage  of  gum  arabic,  782 

of  sassafras  pith,  785 

of  slippery  elm  bark, 

783 

of  tragacanth,  783 
Mucilages,  61 
Mucilagines,  61 
Mucilago  acaciae,  782 

sassafras  medullae,  785 

tragacanthae,  783 

ulmi,  783 
Mulled  wine,  309 
Muriate   of  morphine,   141 
Muriatic  acid,  454 
Muscarine,  antidote  for,  182 
Musk,  73 
Musk-root,  80 
Mustard,  772 


GENERAL   INDEX. 


955 


Mustard  as  an  emetic,  643 

flour,  633 

paper,  773 

plaster,  773 

poultice,  759 
Mutton  suet,  786 
Myristica,  627 

fragrans,  627 
Myrrh,  741 
Myxcedema,  535 

N 

Napelline,  374 
Naphtalenum,  849 
Naphtalin,  849 
Naphthalol,  852 
Naphtol,  850 
Narceine,  142 
Narcotine,  142 
Nataloin,  664 
Nativelle's  digitalin,  312 
Neodermin,  865 
Nervines,  73 
Neural  anaesthesia,  122 
Neurine,  551 
Neutral  mixture,  692 
Ngai  camphor,  (note)  283 
Nicotine,  267 
Nirvanin,  119 
Nitre,  694 
Nitric  acid,  454 

as  a  caustic,  780 

oxide,  82 

poison,  452 
Nitrite-oxyhsemoglobin, 

256 

Nitrogen  monoxide,  82 
Nitroglycerin,  261 
Nitro-hydrochloric  acid, 

455 

poison,  452 
Nitrous  acid,  455 

oxide,  82 
Normal      salt     solution, 

(note)  679 
Norway  spruce,  761 
Nosophen,  515 
Nucleic  acid,  531 
Nucleins,  530 
Nutgall,  406 
Nutmeg,  627 
Nutriants,  401 
Nutritive  enemata,  14 
Nux  vomica,  212 


Oatmeal,  654 
porridge,  12 

Ohm,  45 

Ohm's  law,  42 

Oil  of  absinthe,  860 
of  allspice,  627 
of  anise,  630 


Oil  of  aspic,  (note)  630 
of  bitter  almonds,  394 
of  cajuput,  629 
of  camphor,  288 
of  caraway,  630 
of  chenopodium,  807 
of  cinnamon,  626,  860 
of  cloves,  626,  860 
of  copaiba,  713 
of  coriander,  630 
of  cotton  seed,  787 
of  cubeb,  714 
of  erigeron,  707 
of  eucalyptus,  582 
of  fennel,  630 
of  gaultheria,  597 
of  geranium,  860 
of  hedeoma,  746 
of  juniper,  707 
of  lavender,  630 
of  mace,  627 
of    marjoram,     (note) 

630 
of   mentha    pulegium, 

743 

of  mustard,  772 
of  myristica,  627 
of  nutmeg,  627 
of  pennyroyal,  743 
of  peppermint,  630 

camphor,  852 
of  phosphorus,  468 
of  pimenta,  627 
of  rose,  409 
of    rosemary,    (note) 

630 

of  rue,  742 
of  sandal-wood,    707, 

738,  860 

of  sassafras,  629 
of  savine,  742 
of  spearmint,  630 
of  sweet  almonds,  787 
of  sweet  birch,  597 
of  tansy,  743 
of  tar,  737 
of  theobroma,  787 
of  thyme,  852,  860 
of  turpentine,  708,  774 
of  valerian,  74 
of  vitriol,  453 
of  wine,  heavy,  81 
of  wintergreen,  597 
of  wormseed,  807 
of  zedoary,  860 

Oils,  61 

Ointment    of    ammoniated 

mercury,  496 
of  ammonium  iodide, 

507 

of  antimony,  366 
of  belladonna,  184 
of    fluor-pseudocumol, 

865 

of  galls,  407 
of  iodine,  504 


Ointment  of  iodoform,  513 
of  lead  carbonate,  422 
of  mercuric  nitrate,  496 
of  mercury,  492 
of  mezereon,  529 
of  nutgall,  407 
of  nutmeg,  627 
of    potassium    iodide, 

,5°7^ 

of    red    mercuric    ox- 
ide, 496 

of  rose-water,  409 

of  stramonium,  185 

of  tannic  acid,  405 

of  tar,  737 

of  veratrine,  372 

of    white     precipitate, 
496 

of     yellow      mercuric 
oxide,  496 

of  zinc  oxide,  428 
Ointments,  62 
Olea  destillata,  61 
Oleata,  61 

Oleate  of  mercury,  493 
Oleates,  61,  788 
Oleatum    hydrargyri,    493, 

496 

Oleic  acid,  788 
Oleoresin  of  capsicum,  629 

of  cubeb,  714 

of  fern,  8n 

of  ginger,  628 

of  lupulin,  77 

of  pepper,  628 
Oleoresina  aspidii,  8ir 

capsici,  629 

cubebae,  714 

lupulinae,  77 

piperis,  628 

zingiberis,  628 
Oleoresinae,  61 
Oleoresins,  61 
Oleum  aethereum,  76 

amygdalae  expressum, 

787 

betulae  volatile,  597 
cajuputi,  629 
camphorae,  80 
caryophylli,  626 
chenopodii,  807 
cinnamomi,  626 
copaibae,  713 
cubebae,  714 
erigerontis,  707 
eucalypti,  582 
gaultneriae,  597 
gossypii  seminis,  787 
nedeomae,  743 
juniperi,  707 
lini,  787 
morrhuae,  515 
myristicae,  627 
ohvae,  787 
phosphoratum,  468 
pimentae,  627 


956 


GENERAL    INDEX. 


Oleum  ricini,  659 
sabinae,  742 
santali,  707,  738 
sassafras,  629 
sinapis  volatile,  772 
terebinthinae,  708 
theobromatis,  787 
tiglii,  675 

Olive  oil,  787 

Onaye  poison,  334 

Opii  pulvis,  140 

Opinanine,  125 

Opium,  125 

alkaloids,  142 
deodoratum,  140 
deodorized,  140 
poisoning  by,  126,  135 
smoking,  139 

Orange-flower  water,  630 
flowers,  630 
peel,  629 

Orexae  hydrochloras,  624 

Orexin,  624 

tannate,  624 

Orthocresol,  848 

Orthocresotic  acid,  (note) 

589 

Orthoform,  118 
Orthoguaiacol-sulphonic 

acid,  847 
Oxalic  acid,  397 

poisoning,  398 
Oxgall,  655 
Oxide  of  gold,  498 

of  zinc,  428 
Oxidizing    disinfectants, 

826 

Oxycamphor,  289 
Oxycannabin,  191 
Oxydicolchicine,  521 
Oxysparteine,    (note)    350 
Oxytocics,  745 


Pahouius  poison,  334 
Pale  catechu,  407 

cinchona,  555 

rose,  409 
Pancreatin,  816 
Pancreatized  foods,  14 
Papain,  817 

Papaver  somniferum,  125 
Papaverine,  142 
Papaw,  817 
Papayotin,  817 
Papers,  62 
Paracetamidophenol , 

(note)  611 
Paracresol,  848 
Paracresotic  acid,  (note) 

589 

Paraffin,  792 
Paraffinum,  792 
Paraform,  858 


Paraform  aldehyde,  857 
Paraguay  tea,   (note)  338 
Paraldehyde,  160 
Paraldehydum,  160 
Paramidophenol,  (note) 

611,  614 

Paramorphine,  125 
Paraphenetidin-vanillin- 

ethyl-carbonate,  610 
Paraxanthin,  685 
Paregoric,  141 
Pareira,  705 

brava,  705 
Parillin,  528 
Parillinic  acid,  528 
Parsley,  743 
Paullinia  campana,  339 
Pearl  barley,  785 
Pearlash,  691 
Pelletierinae  tannas,  813 
Pelletierine,  813 
Pennyroyal,  743 
Pental,  102 
Pepo,  812 
Pepper,  628 
Peppermint,  630 

water,  630 
Pepsin,  815 
Pepsinum,  815 
Peptonized  beef  tea,  14 

gruel,  14 

milk,  14 

milk  toast,  14 

oysters,  14 
Pernambuco    jaborandi, 

720 

Peronine,  142 
Peroxide  of  hydrogen, 

828 

Pertussin,  853 
Pest  serum,  549 
Petrolatum,  792 

album,  792 

liquidum,  792 
Petroselinum  sativum,  743 
Pharmacodynamics,  60 
Pharmacology,  60 
Pharmacopoeia,  60 
Pharmacy,  60 
Phellandrene,  582 
Phenacetin,  614 
Phenazonum,  600 
Phenic  acid,  831 
Phenocoll  hydrochloride, 

616 
Phenol,  831 

liquefactum,  831 

poisoning,  838 

sodique,  874 
Phenosol,  618 
Phenyl  sal  icy  late,  847 
Phenylacetamide,  610 
Phenyldihydrochinazoline 

hydrochlorate,  624 
Phenyl-dimethyl-pyrazo- 
lone,  600 


Phenylic  alcohol,  831 
Phenylis  salicylas,  847 
Phosphorated  oil,  468 
Phosphoric  acid,  518 
Phosphorus,  459 

antidote  to,  466 

necrosis,  468 

poisoning,  461 

sesquisulphide,   (note) 

468 
Physostigma,  229 

poisoning,  238 

venenosum,  229 
Physostigminae      salicylas, 
238 

sulphas,  238 
Physostigmine,  229 

sal  icy  late,  238 

sulphate,  238 
Picraconitine,  374 
Picrsena  excelsa,  622 
Picric  acid,  814 
Picropodophyllin,      (note) 

672 
Pill  of  aloes,  666 

of  aloes  and  asafetida, 
164 

of  aloes  and  iron,  666 

of  aloes  and  mastic, 
666 

of  aloes     and     myrrh, 
666 

of  asafetida,  76 

of  opium,  140 

of  phosphorus,  468 

of  podophyllum,  capsi- 
cum, and  belladonna, 

673 

of  rhubarb,     com- 
pound, 663 
Pills,  62 

Pilocarpidine,  (note)  721 
Pilocarpinae   hydrochloras, 

727 
Pilocarpine,  721 

hydrochlorate,  727 
Pilocarpus,  720 
jaborandi,  720 
pinnatus,  (note)  720 
selloanus,  720 
Pilulae,  62 

aloes,  666 

aloes     et      asafcetidae, 

666 

aloes  et  ferri,  666 
aloes    et     mastiches, 

666 

aloes  et  myrrhae,  666 
asafoetidae,  76 
catharticae  compositae, 

672 
catharticae  vegetabiles, 

672 
taxativas   compositae, 

666 
opii,  140 


GENERAL    INDEX. 


957 


Pilulae  phosphpri,  468 

podophylli,    capsici   et 
belladonnas,  673 

rhei  composite,  663 
Pimenta,  627 

officinalis,  627 
Pimpinella  anisum,  630 
Pinkroot,  805 
Pinus  palustris,  708,  737 
Pipe  gamboge,  675 
Piper,  628 

angustifolium,  714 

cubeba,  713 

methysticum,  715 

nigrum,  628 
Piperazidine,  698 
Piperazinae  quinas,  701 
Piperazine,  698 

hydrochlorate,  698 
Piperazinum,  698 
Piperin,  628 
Piperinum,  628 
Pipsissewa,  706 
Pitch,  737 
Pjtuitary  body,  543 
Pix  burgundica,  775 

liquida,  737 
Plasma  of  starch,  791 
Plaster  of  ammoniac   with 
mercury,  739 

of  belladonna,  184 

of  mercury,  496 
Plasters,  62 
Platt's  chlorides,  874 
Plumbi  acetas,  421 

carbonas,  422 

nitras,  423 

oxidum,  421 
Plumbism,  412 
Plumbum,  411 
Podophyllin,  673 
Podophyllinic  acid,  (note) 

672 

Podophylloresin,  672 
Podophyllotoxin,  651,   672 
Podophyllum,  672 

peltatum,  672 
Polygala  senega,  739 
Polygalic  acid,  739 
Polymerized    formalde- 
hyde, (note)  858 
Polystichic  acid,    (note) 

Sii 

Pomegranate  rind,  813 
Poppy,  125 
Porcelain  clay,  793 
Porphyroxine,  142 
Potash,  691 
Potassa  cum  calce,  778 

sulphurata,  658 
Potassii  acetas,  692 

bicarbonas,  691 

bitartras,  693 

bromidum,  239 

carbonas,  691 

chloras,  695 


Potassii  citras,  692 

cyanidum,  393 

et  sodii  tartras,  669 

hydroxidum,  777 

hypophosphis,  521 

iqdidum,  505 

nitras,  694 

permanganas,  826 

sulphas,  693 
Potassium,  687 

acetate,  692 

alum,  410 

and    sodium     tartrate, 
669 

bicarbonate,  691 

bi tartrate,  693 

bromide,  239 

carbonate,  691 

chlorate,  695 

poisoning  by,  695 

citrate,  692,  733 

cyanide,  393 

hypophosphite,  521 

iodide,  505 

myronate,  772 

nitrate,  694 

poisoning  by,    694 

nitrite,  260 

oxalate,  398 

permanganate,  741,  826 

sulphate.  693 
Poudre      de      succession, 

(note)  411 
Poultices,  793 
Powder     of     ipecac     and 

opium,  140 
Powdered  opium,  140 
Powders,  62 
Practical  anaesthesia,  103 

disinfection,  869 

local  anaesthesia,  1 19 
Precipitated    calcium    car- 
bonate, 803 

calcium  phosphate,  520 

sulphur,  657 

zinc  carbonate,  428 
Predigested  foods,  13 
Preparations  of  drugs,  60 
Prepared  chalk,  803 
Prescribing,  art  of,  67 
Prickly  pear,  530 
Pride  of  China,  806 
Primary  current,  46 
Propenyl  alcohol,  788 
Proprietary     disinfectants, 

(note)  825 
Propylamin,  516 
Protargol,  440 
Protect)  ves,  796 
Protiodide  of  mercury,  495 
Prunes,  654 
Prunus  serotina,  624 

virginiana,  624 
Prussic  acid,  385 

poisoning,  392 
Pseudaconitine,  (note)  374 


Pseudocannabinol,  192 
Pseudojervine,  366 
Psychotrin,  635 
Pterocarpus      marsupium, 

407 

Ptyalism,  484 
Pulveres,  62 
Pulvis  aromaticus,  626 

effervescens    composi- 
tus,  669 

glycyrrhiza      composi- 
tus,  667,  784 

ipecacuanhas    et    opii, 
140,  728 

jalapae  compositus,  670 

parturiens,  751 

rhei  compositus,  663 
Pumpkin  seed,  812 
Punicine,  813 
Purgative  enemas,  650 
Purgatives,  644 

hypodermic  use  of,  651 
Purges,  659 
Purging  agaric,  409 

cassia,  656 
Purified  aloes,  665 

animal  charcoal,  819 

oxgall,  655 
Purshianin,  655 
Pyramidon,  617 

bicamphorate,  618 

camphorate,  618    . 

salicylate,  618 
Pyroacetic     spirit,     (note) 

397 

Pyrocatechin,  854 
Pyrogallic  acid,  781 
Pyrogallol,  781 
Pyrosal,  618 
Pyroxylic  spirits,  311 
Pyroxylin,  796 
Pyroxylinum,  796 


Quassia,  622 
Quassin,  622 
Quebrachamine,  277 
Quebrachine,  277 
Quebracho,  277 
Queen's  root,  530 

euercitron,  408 
uercus  alba,  409 
lusitanica,  406 
tinctoria,  408 
Quevenne's  iron,  448 
Quillaja,  739 

Buinic  acid,  701 
uinicine,  555 
Quinidinae  sulphas,  577 
Quinidine  sulphate,  577 
Qujnina,  556 
Quininae  bisulphas,  575 
hydrobromas,  575 
hydrochloras,  575 


GENERAL   INDEX. 


Quininae  sulphas,  556 
Quinine,  556 

bisulphate,  575 

dihydroxyl,  (note)  559 

esters,  579 

hydrobromate,  575 

hydrochlorate,  575 

poisoning,  576 

salicylate,  575 

sulphate,  556 

tannate,  577 
Quinotropine,  701 


Reactions  of  degeneration, 

53 

Rectal  alimentation,  14 
Red  cinchona,  555 

gum,  582 

mercuric  iodide,  495 

mercuric  oxide,  496 

precipitate  ointment, 
496 

wine,  289 

Reduced  iron,  448 
Refrigerants,  394 
Relation    of    apothecaries' 
to  metric  weights, 
881 

of  apothecaries' 
weights   to  meas- 
ures, 88 1 

of  metric  to  apotheca- 
ries' weights,  881 
Remijia  pedunculata,  578 

purdieana,  578 
Rennet,  815 
Resin  cerate,  708 

of  jalap,  671 

of  May-apple,  673 

of  podophyllum,  673 

of  scammony,  672 

plaster,  421 
Resina,  708 

jalapae,  671 

podophylli,  673 

scammonii,  672 
Resinae,  62 
Resins,  62 
Resorcin,  854 
Resorcinol,  854 
Respiratory  depressants, 
276 

stimulants,  276 
Rest-cure,  17 
Rhabarbarin,  663 
Rhamnus  frangula,  655 

purshiana,  655 
Rhatany,  408 
Rhein,  663 
Rheum,  662 

officinale,  662 
Rheumatine,  579 
Rhodalline,  529 


Rhodeoretin,  670 
Rhubarb,  662 
Rhus  glabra,  409 
Ricin,  659 
Ricinoleic  acid,  659 
Ricinolein,  659 
Ricinus  communis,  659 
Rio  Janeiro  jaborandi,  720 
Rochelle  salt,  669 
Roman  chamomile,  631 
Rosa  centifolia,  409 

gallica,  409 
Rosemary,    oil  of,    (note) 

630 

Rose-water,  409 
Rosin,  708 
Roth-Drager  inhaler, 

(note)  104 
Rottlerin,  814 
Rubefacients,  772 
Rubijervine,  366 
Rubraronic  acid,  617 
Rue,  742 

Russian  bath.  717 
Ruta,  742 

graveolens,  742 
Rye,  745 


Sabadilline,  (note)  370 
Sabina,  742 

Saccharated    ferrous    car- 
bonate, 448 

ferrous  iodide,  450 

pepsin,  815 
Saccharin,  791 
Saccharum,  654 

lactis,  654 
Sage,  630 
Sago  jelly,  12 

porridge,  12 
Saigon  cinnamon,  626 
Saljcin,  599 
Salicyl-acetic    acid  phene- 

tide,  618 
Salicylate  of  /i-naphtol 

ether,  852 
Salicylic  acid,  587 

amylester,  599 

methyloxymethyl- 

ester,  599 

Sahcylunc  acid,  588 
Salines,  667 
Salipyrin,  617 
Salol,  847 
Salophen,  599 
Saloquinine,  579 
Salseparin,  528 
Salt  of  lemons,   essential, 

398 

of  sorrel,  398 
Saltpetre,  694 
Salvia,  630 

officinalis,  630 


Sanguinaria,  739 
Sanguinarine,  739 
Santalum  album,  707,  738 
Santogenin,  808 
Santonica,  807 
Santonin,  807 
Santoninic  acid,  807 
Santoninum,  807 
Sapo,  765 

mollis,  765 

viride,  765 
Saponin,  528,  739 
Sarillinic  acid,  528 
Sarsaparilla,  528 
Sarsaparillin,  528 
Sarsaponin,  528 
Sassafras,  oil  of,  629 

pith,  785 

Saturnine  cerebritis,  414 
Saturnism,  412 
Savine,  742 
Scammonin,  671 
Scammonium,  671 
Scammony,  671 
Scheele's  green,  479 
Schleich's  infiltration- 
anaesthesia,  119 

mixture,  (note)  106 
Schweinfurt  green,  479 
Scilla,  680,  737 
Scillin,  680 
Scillipicrin,  680 
Scillitin,  681 
Scillitoxin,  680 
Scoparin,  682 
Scoparius,  682 
Scopola,  1 86 

carniolica,  186 

japonica,  186 
Scopolamine,  186 

hydrobromide,  187 

-morphine  anaesthesia, 

189 

Secale  cereale,  745 
Seidlitz  powder,  669 
Senega,  739 
Senegin,  739 
Senna,  666 
Serpentaria,  631 
Serum  antidiphthericum, 

545 

Sevum,  786 

Sex  in  relation  to  dose,  66 

Shore  oil,  515 

Sjdonal,  701 

Silberol,  439 

Silver,  431 

acetate,  438 
citrate,  438 
cyanide,  394,  438 
fluoride,  865 
iodide,  438 
lactate,  438 
nitrate,  431,  822 
nitrate,  diluted,  438 
nitrate,  fused,  431 


GENERAL   INDEX. 


959 


Silver  oxide,  438 
poisoning,  436 
soluble,  439 
sulphocarbolate,  439 
thiohydrocarbosul- 

phonate,  440 
vitellin,  438 
Simaruba,  622 

officinalis,  622 
Simple  bitters,  622 
Sinalbin,  772 
Sinapis  alba,  772 

nigra, 772 
Sinigrin,  772 
Siphon   stomach-pump, 

(note)  136 
Slippery  elm,  783 

poultice,  794 
Smilacin,  528 
Smilax,  528 
Smyrna  opium,  125 
Snake-poisoning  anti- 
toxin, 550 
Soap,  765 

liniment,  288 
plaster.  421,  796 
Soap-bark,  739 
Socaloin,  664 
Socotrine  aloes,  664 
Soda,  798 
Sodii  acetas,  Soi 
arsenas,  482 
benzoas,  864 
bicarbonas,  801 
bicarbonas  venalis,  Soi 
boras,  866 
bromidum,  248 
carbonas  exsiccatus, 

801 
carbonas  monohydras, 

801 

hydroxidum,  Soo 
hypophosphis,  521 
nitras,  80 1 
nitris,  260 

phenolsulphonas,  849 
phosphas,  668 
phosphas  effervescens, 

669 
phosphas   exsiccatus, 

669 

salicylas,  596 
sulphas,  668 
Sodium,  798 
acetate,  80 1 
and  caffeine  benzoate, 

348 
and  theobromine  sali- 

cylate,  684 
arsenate,  482 
benzoate,  864 
bicarbonate,  801 
borate,  866 
bromide,  248 
carbonate,  801 
carbonate,  dried,  801 


Sodium    chlorate,    ( note 

697 

cinnamate,  864 
fluoride,  865 
hydrate,  8po,  874 
hypochlorite,  826 
hypophosphite,  521 
ichthyo-sulphate,  527 
lactate,  457 
nitrate,  694,  801 
nitrite,  260 
phosphate,  668 
salicylate,  596 
santoninate,  810 
sulphate,  668 
sulphocarbolate,  849 
tartrate,  669 
tetraiodophenol- 
phthalein,  515 
theobromine  salicyl- 
ate, 684 

Soft  soap,  765 

Solid  extracts,  61 

Soluble    ferric    phosphate, 

45 ' 
ferric  pyrophosphate, 

45i 

iron  and  quinine  cit- 
rate, 451 

silver,  439 
Solution  of  ammonium 
acetate,  728 

of  arsenic  and   mer- 
curic iodide,  507 

of  arsenous  acid,  482 

of  chlorinated  soda, 
825 

of  ferric  subsulphate, 

449 

of  ferric  sulphate,  449 
of  formaldehyde,  856 
of  gutta-percha,    796 
of  hydrogen  dioxide, 

828 
of  hydrogen  peroxide, 

828 

of  lead  subacetate,  422 
of  lime,  802 
of  magnesium  citrate, 

668 
of  mercuric  nitrate, 

779 
of  persulphate  of  iron, 

449 

of  potassa,  692 
of  potassium  arsenite, 

482 
of   potassium  citrate, 

692 
of  sodium   arsenate, 

482 

of  sodium  hydrate,  800 
of  subsulphate  of  iron, 

449 

of  zinc  chloride,  779 
Solutions,  61 


Somnifacients,  125 

minor,  162 
Somnoform,  103 
Soups,  9 
Soziodol,  515 
Spanish  flies,  769 
Sparteinse  sulphas,  350 
Sparteine,  350 

sulphate,  350,  354 
Spasmodic  ergotism,  755 
Spearmint,  630 
water,  630 
Spermaceti,  786 
Sphacelinic  acid,  746 
Sphacelotoxin,  746 
Spjce  plasters,  773 
Spigeha,  805 

marilandica,  805 
Spigeline,  806 
Spinal  anaesthesia,  121 
Spirit  of  ammonia,  282 
aromatic,  282 

of  anise,  630 

of  camphor,  288 

of  chloroform,  100 

of  cinnamon,  626 

of  ether,  76 

of  ether,   compound, 
76 

of  glonoin,  261 

of  juniper,  707 

of  juniper,  compound, 
707 

of  lavender,  631 

of  lemon,  630 

of  Mindererus,  728 

of  nitrous  ether,  685, 
728 

of  peppermint,  630 

of  spearmint,  630 
Spirits,  61 
Spiritus,  6 1 

aetheris,  76 

aetheris  compositus,  76 

aetheris   nitrosi,   685, 
728 

ammonise,  282 

ammoniae  aromaticus, 
282 

anisi,  630 

camphorae,  288 

chloroformi,  rco 

cinnamomi,  626 

frumenti,  289 

glonoini,  261 

glycerylis  nitralis,  261 

jtiniperi,  707 

juniperi   compositus, 
707 

lavandulae,  631 

limonis,  630 

menthae  piperitae,  630 

vini  gallici,  289 
Spleen,  543 
Squill,  680 

as  an  expectorant,  737 


960 


GENERAL    INDEX. 


Squirting  cucumber,  673 
Star  anise,  630 
Starch,  784 
Stearic  acid,  788 
Sterculia  acuminata,  338 
Sticking  plaster,  422,  708 
Stillingia,  530 
Stillingine,  530 
Stimulating  emetics,  643 
Stomachics,  621 
Stomach-pump,  (note)  136 
Stovaine,  118 
Straits  oil,  515 
Stramonii  folia,  185 
Stramonium  leaves,  185 

seed,  185 

Streptococcus  antitoxin, 
548 

toxin,  545 

Stronger  water  of  ammo- 
nia, 282 
Strontii  bromidum,  249 

iodidum,  508 

lactas,  704 
Strontium,  702 

bromide,  249 

iodide,  508 

lactate,  704 

phosphate,   (note)  703 

salicylate,  596 
Strophanthidin,  334 
Strophanthin,  334,  338 
Strophanthus,  334 

hispidus,  334 

kombe',  334 
Strychnic  acid,  214 
Strychnina,  212 

poisoning  by,  222 
Strychninae  sulphas,  212 
Strychnine   sulphate,   212, 

226 

Strychnos  nux  vomica,  212 
Stupes,  774 
Styptic  collodion,  405 
Stypticin,  409 
Styptics,  402 
Styrax  benzoin,  861 
Subacute  lead-poisoning, 

412 
Subcutaneous   injections, 

64 

Subcutin,  118 
Sublimed  sulphur,  657 
Succi,  61 
Succinic  acid,  862 
Succus  limonis,  396 
Suet,  786 
Sugar,  687 

as  a  diuretic,  687 

of  lead,  421 

of  milk,  654,  687 
Sulphites,  862 
Sulpho-carbolic  acid,  849 
Sulphonal,  155 

poisoning,  157 
Sulphur,  657 


Sulphur  dioxide,  865 

lotum,  657 

praecipitatum,  657 

sublimatum,  657 
Sulphurated  lime,  658 

potassa,  658 
Sulphuretted   hydrogen, 

740 
Sulphuric  acid,  453,  874 

poisoning,  453 
Sulphurous  acid,  864 
Sumach,  409 
Sumbul,  80 
Suppositoria,  62 
Suppositories,  62,  65 

urethral,  65 
Suprarenal  capsule,  538 
Suprarenin,  539 
Sweet  orange  peel,  630 

spirit  of  nitre,   685, 
728 

tincture  of  rhubarb, 

664 

Swertia  chirata,  623 
Sydenham's   laudanum, 

141 
Syrup,  Coxe's  hive,  737 

of  althaea,  785 

of  ferrous  iodide,  450 

of  garlic,  737 

of  ginger,  628 

of  nydriodic  acid,  504 

of  hypophosphites,  521 

of  iodide  of  iron,  450 

of  ipecacuanha,  639 

of  lactucarium,  80 

of  lime,  802 

of  rhubarb,  664 

of  rhubarb,    aromatic, 
664 

of  rose,  409 

of  sarsaparilla,  com- 
pound, 528 

of  senega,  739 

of  senna,  667 

of  squill,  682,  737 

of  squill,    compound, 

737 
of  sweet  orange  peel, 

630 

of  tar,  738 
of  Tplu,  736 
of  wild  cherry,  624 
Syrupi,  61 
Syrups,  61 
Syrupus   acidi    hydriodici, 

504 

allii,  737 
althseae,  785 
aurantii.  630 
calcis,  802 
ferri  iodidi,  450 
fuscus,  654 
hypophosphitum,  521 
hypophosphitum  com- 
positum,  521 


Syrupus  ipecacuanhae,  639 
lactucarii,  80 
picis  liquicke,  738 
pruni  virginiance,  624 
rhei,  664 

rhei  aromaticus,  664 
rosae,  409 
sarsaparilUe    composi- 

tus,  529 
scillae,  682,  737 
scilke  compositus,  737 
senegae,  739 
sennas,  667 
tolutanus,  736 
zingiberis,  628 
Systemic    lavage,    (note) 

209 
Syzygium   jambolanum, 

extract    of,    (note) 

398 


Tabacum,  267 

Table  of  apothecaries' 

weights  and  meas- 
ures, 879 

Table  of  composition  of 
foods,  23 

Table  of  cost  of  various 
disinfectants,  (note) 
825 

Table  of  germicides,  874 

Table  of  the  proportion 
of  alcohol  in  different 
wines,  882 

Table  of  relation  of  apoth- 
ecaries' weights  to 
metrical  weights,  880 

Table  of  relation  of  apoth- 
ecaries' weights  and 
measures  to  eacli 
other,  880 

Table  of  weights  and 
measures  of  the  met- 
rical system,  879 

Tachiol,  865 

Tamarind,  656 

Tamarindus,  656 
indica,  656 

Tanacetum,  743 
vulgare,  743 

Tannacol,  405 

Tannalbin,  405 

Tannate  of  cannabene,  195 
of  quinine,  577 

Tannic  acid,  402 
compounds,  405 

Tannin  albuminate,  405 

Tannoform,  405 

Tannopine,  405 

Tannon,  405 

Tansy,  743 

Tapioca  porridge,  13 

Tar,  737 


GENERAL    INDEX. 


961 


Tar  camphor,  849 
Taraxacum,  530 

officinale,  530 
Tartar,  335 

emetic,  360,  733 

poisoning,  394 
Tartaric  acid,  394 

poisoning,  395 
Tea,  338 

Temperament,  66 
Terebene,  738 
Terebenum,  738 
Terebinthina,  708 

canadensis,  708 
Terpin  hydrate,  738 
Terpini  hydras,  738 
Tertiary  amyl  nitrite, 

(note)  252 

Tetano-cannabene,  191 
Tetanus  antitoxin,  547 
Tetra-iodo-phenol-phtha- 

lein,  515 

Tetra-iodopyrrol,  514 
Tetra-methylthionine  hy- 

drochloride,  580 
Tetronal,  59 
Thebaine,   142 
Thebolactic  acid,  125 
Theine,  338 
Theobromine,  684 

and  sodium  salicylate, 

684 

Theocin,  685 
Theocol,  847 
Theophyllin,  685 
Thermol,  618 
Thioresorcin,  (note)  854 
Thiosinamine,  529 
Thymacetin,  853 
Thymol,  813,  852 
Thymolis  iodidum,  514 
Thymus  serpyllum,  (note) 
852 

vulgaris,  (note)  852 
Thyreoantitoxin,  535 
Thyroid  body,  534 
Thyroidismus,  536 
Thyroiodin,  535 
Time  for  administration 

of  drugs,  67 
Tinctura  aconiti,  385 

aloes,  666 

aloes  et  myrrhae,  666 

arnicae,  373 

asafcetidae,  76 

aurantii  amari,  630 

aurantii  dulcis,  630 

belladonnae  foliorum, 
184 

benzoin!,  863 

benzoini  composita, 
863 

calumbae,  623 

cannabis  indicae,  195 

cantharidis,  772 

capsici,  629 


Tinctura  cardamomi,  627 
cardamomi  composita, 

627 

chiratae,  623 
cimicifugae,  79 
cinchonas  composita, 

.555 

cinnamomi,  626 
colchici  seminis,  527 
digitalis,  330      • 
ferri  chloridi,  449 
gallse,  407 
gambir,  407 
gambir  composita,  407 
gelsemii,  267 
gentiame  composita, 

623 

guaiaci,  529 
guaiaci    ammoniata, 

529 

humuli,  77 
hydrastis,  760 
hyoscyami,  186 
iodi,  504 
ipecacuanhas  et  opii, 

i-I4T 
kino,  407 

krameriae,  408 
lactucarii,  80 
lobelias,  264,  733 
matico,  714 
moschi,  74 
nucis  vomicae,  212 
opii,  141 

opii  camphorata,  141 
opii  deodorati,  141 
physostigmatis,  238 
quassiae,  622 
rhei,  664 

rhei  aromatica,  662 
scillae,  682 
serpentarias,  631 
stramonii,  185 
strophanthi,  338 
tolutana,  736 
valerianae,  75 
valerianas   ammoniata, 

75 

veratn,  370 

zingibens,  628 
Tincturee,  61 
Tincture  of  aconite,  3.85 

of  aconite,   Fleming's, 

385 

of  aloes,  666 
of  aloes  and   myrrh, 

666 

of  arnica,  373 
of  asafetida,  76 
of  belladonna    leaves, 

184 

of  benzoin,  863 
of  benzoin,  compound, 

863 
of  bitter  orange  peel,  | 

630 

61 


Tincture  of  cannabis  indica, 

J95 

of  cantharides,  772 
of  capsicum,  629 
of  cardamom,  627 
of  cardamom,    com- 
pound, 627 
of  chirata,  623 
of  chloride  of  iron,  449 
of  cimicifuga,  79 
of  cinchona,   com- 
pound, 555 
of  cinnamon,  626 
of  colchicum  seeds, 

527 

of  columbo,  623 
of  conium,  273 
of  digitalis,  330 
of  ferric  chloride,  449 
of  galls,  407 
of  gambir,  407 
of  gelsemium,  267 
of  gentian,  compound, 

623 

of  ginger,  628 
of  guaiac,  529 
of  guaiac,  ammo- 

niated,  529 
of  hemp,  195 
of  hops,  77 
of  hydrastis,  760 
of  hyoscyamus,  186 
of  Indian  cannabis, 

195 

of  iodine,  504 

of  ipecac  and  opium, 
141 

of  kino,  407 

of  krameria,  408 

of  lactucarium,  80 

of  lobelia,  264,  733 

of  matico,  714 

of  mufck,  74 

of  nutgall,  407 

of  nux  vomica,  212 

of  opium,  141 

of  opium,  camphor- 
ated, 141 

of  opium,  deodorized, 
141 

of  physostigma,  238 

of  quassia,  622 

of  rhatany,  408 

of  rhubarb,  664 
aromatic,  664 
sweet,  664 

of  serpentaria,  631 

of  squill,  682 

of  stramonium,  185 

of  strophanthus,  338 

of  sweet  orange  peel, 
630 

of  Tolu,  736 

of  valerian,  75 

of    valerian,    ammoni- 
ated,  75 


962 


GENERAL    INDEX. 


Tincture  of  veratrum  viride, 

370 

Tinctures,  61 
Tinnevelly  senna,  666 
Tobacco,  267 
Toluifera  balsamum,  736 

pereirs,  736 
Tomato  porridge,  12 
Tonics,  443 
Toxins  and  antitoxins,  544 
Tragacanth,  783 
Tragacantha,  783 
Trichlor  tertiary  butyl 

alcohol,  162 
Trichloracetic  acid,  780 
Trichlorisopropyl    alcohol, 

163 

Trimethylamin,  516 
Trimethylethylene,  102 
Trimethylxanthin,  683 
Trinitro-cellulose,  796 
Trional,  159 
Trioxymethylanthraqui- 
none,  (note)  663 
Triticum,  706 
Triturate  of  elaterin,  674 
Trituratio  elaterini,  674 
Troches,  62 

of  gambir,  407 

of  ipecac,  639 

of  ipecac  and   mor- 
phine, 639 

of  santonin,  Sio 

of  tannic  acid,  405 
Trochisci,  62 

acidi  tannici,  405 

gambir,  407 

ipecacuanha?,  639 

morphinas  et   ipecacu- 
anha?, 639 

santonini,  810 
Tropacocaine,  117 
Tropine,  (note)  168 
True  chamomile,  631 

expectorants,  732 
Tuberculin,  544 
Turkey  opium,  125 
Turkish  bath,  717 
Turpentine,  708 

as  an  anthelmintic, 
812 

enemata,  650 

liniment,  774 

-phosphoric  acid,  467 

stupes,  774 
Turpeth  mineral,  496 


U 

Ulmus,  783 

fulva,  783 

Unbolted  flour,  654 
Unguenta,  62 

Unguentum    acidi   tannici, 
405 


Unguentum     aquae    ros;e, 

409,  786 

belladonna;,  184 
gallae,  407 
hydrargyri,  492 
hydrargyri    amnio- 

niati,  496 

hydrargyri  nitratis,  496 
hydrargyri  oxidi  flavi, 

496 

oxidi  rubri,  496 
iodi,  504 
iodoformi,  513 
mezerei,  529 
picis  liquidae,  737 
plumbi  carbonatis,  422 
potassii  iodidi,  507 
stramonii,  185 
veratrinae,  372 
zinci  oxidi,  428 

Unslaked  lime,  801 

Urasol,  702 

Urethane,  163 

Urethral  suppositories,   65 

Urginea  maritima,  680 

Urochloralic  acid,  146 

Urohaematoporphyrine, 
416 

Urotropin,  699 

Urotropinse  quinas,  701 

Uva  ursi,  705 


Valerian,  74 
Valeriana,  74 

officinalis,  74 
Valerianic  acid,  74 

dimethylamid,  75 
Valjdol,  75 
Validolum  camphoratum, 

75 
Vapor  bath,  717 

creosoti,  845 
Vaseline,  792 
Vegetable  acids,  394 

astringents,  402 

cathartic  pills,  672 
Veratralbine,  366 
Veratrina,  370 
Veratrine,  366 

ointment,  372 
Veratroidine,  366 
Veratrum,  366 

album,  366 

sabadilla,  370 

viride,  366 

viride,   poisoning  by, 

369 

Vermicelli  soup,  10 
Vermicides,  805 
Vermifuges,  805 
Veronal,  164 
Veronica  virginica,  656 
Vesicatories,  769 


Viburnum  opulus,  744 
prunifolium,  744 

Vienna  paste,  778 

Vina,  6 1 

Vinegar,  396 

of  opium,  141 
of  squill,  682 

Vinegars,  61,  396 

Vinum  album,  289 
antimonii,  366 
colchici  radicis,  527 
colchici  seminis,  527 
ergotie,  756 
ipecacuanha;,  639 
opii;  141 
rubrum,  289 

Virgin  scammony,  672 

Virginia  snakeroot,  631 

Volatile  oil  of  hops,  82 
oil  of  mustard,  772 
oil  of  savine,  742 
oils,  61,  860 

Volt,  45 

Volta's  law,  41 


W 

Wahoo,  653 

Warburg's  tincture,  579 

Warming  plaster,  775 

Washed  sulphur,  657 

Water  as  a  diuretic,  678 
of  ammonia,  282 
of  chloroform,  100 
of  creosote,  845 
of  hamamelis,  408 
of  rosemary,  631 

Waters,  61 

Wax,  786 

white,  772,  786 

Weights  and  measures, 
879 

West  India  pepper,  629 

Whiskey,  289 

White  agaric,  409 
arsenic,  468 
galls,  407 
ginger,  628 
hellebore,  370 
mustard,  772 
oak,  408 
pepper,  628 
precipitate,  496 
precipitate  ointment, 

496 

sugar,  654 
turpentine,  708 
vitriol,  427 
wax,  786 
wine,  289 

Wigger's  ergotin,  756 

Wild  cherry,  624 

Williamson's  sanitary 
fluid,  8n 

Wine,  289 


GENERAL   INDEX. 


963 


Wine  of  antimony,  366 
of    colchicum    root, 

527 

of  colchicum  seed,  527 

of  ergot,  756 

of  ipecacuanha,  635 

of  opium,  141 

whey,  u,  309 
Wines,  61 
Wormseed,  806 

oil,  807 

Wood  alcohol,  311 
Wool  fat,  788 


X 

Xanthin,  683 
Xanthopuccine,  754 
Xanthoxylum,  530 
Xylic  acid,  831 


Yaupon,  338 

Yellow  cinchona,  555 
gentian,  622 
jessamine,  264 
mercuric  oxide,  496 
mercuric   subsulphate, 

496 

mercurous  iodide,  495 
prussiateof  potash,  430 
wash,  496 
wax,  786 

Yohimbine,  715 

Young's  rule  for  doses,  65 


Zinc,  427 

acetate,  428 


Zinc  bromide,  428 

carbonate,   precipi- 
tated, 428 

chloride,  778,  823 

oxide,  427 

phosphide,  468 

poisoning,  427 

sulphate,  427,  643,  823 
Zinci  acetas,  403 

bromidum,  428 

carbonas  pnecipitatus, 
428 

chloridum,  778 

oxidum,  427 

oxidum  venale,  427 

phosphidum,  468 

sulphas,  427 

sulphocarbolate,  849 
Zincum,  427 
Zingiber,  627 

officinale,  627 


THE   END. 


Kn 


THE  LIBRARY 
UNIVERSITY  OF  CALIFORNIA 

Santa  Barbara 


THIS  BOOK  IS  DUE  ON  THE  LAST  DATE 
STAMPED  BELOW. 


Series  9482 


